[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Oncotherapeutics\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":112},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,43,67,88],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":28,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":32,"startDateStruct":35,"completionDateStruct":37,"leadSponsor":39,"locationsCount":42},"100533399","phase-1-a-trial-of-selinexor-ruxolitinib-and-methylprednisolone-100533399",false,"NCT06225310","A Trial of Selinexor, Ruxolitinib and Methylprednisolone","A Phase I Trial of Selinexor, Ruxolitinib and Methylprednisolone for Patients With Relapsed\u002FRefractory Multiple Myeloma","KPT-IST-391","Inclusion Criteria:\n\nPatients must meet all the following inclusion criteria to be eligible to enroll in this study:\n\n1\\. Has a diagnosis of MM based on standard criteria as follows:\n\nMyeloma criteria: Must be At least 1 of 2 1. Clonal bone marrow plasma cells \\>10% 2. Biopsy-proven bony or extramedullary plasmacytoma\n\nActive Myeloma criteria: Active Myeloma criteria: Must Meet At Least ONE of the Following:\n\nMeet at least one of the sub-criteria for #1 Evidence of End Organ Damage (a, b, c, or d), OR Meet sub-criteria #2. 60% or greater bone marrow plasma cells, OR Meet sub-criteria #3 Serum free light chain ratio, OR Meet sub-criteria #4 More than one focal lesion on MRI \\> 5mm in size.\n\n1. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically\n\n   1. Hypercalcemia: serum calcium \\>0.25 mmol\u002FL (\\>1mg\u002FdL) higher than the upper limit of normal or \\>2.75 mmol\u002FL (\\>11mg\u002FdL)\n   2. Renal insufficiency: creatinine clearance \\\u003C40 mL per minute or serum creatinine \\>177mol\u002FL (\\>2mg\u002FdL)\n   3. Anemia: hemoglobin value of \\>20g\u002FL below the lowest limit of normal, or a hemoglobin value \\\u003C100g\u002FL\n   4. Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or PET\u002FCT. If bone marrow has \\\u003C10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement\n2. 60% or greater clonal plasma cells on bone marrow examination\n3. Serum involved \u002F uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved light chain is at least 100 mg\u002FL (a patient's involved free light chain either kappa or lambda is the one that is above the normal reference range; the uninvolved free light chain is the one that is typically in, or below, the normal range)\n4. More than one focal lesion on MRI that is at least 5mm or greater in size\n\nThe patient must have met the criteria for Active Myeloma at some stage following the diagnosis of Myeloma. Source documentation for both Myeloma and Active Myeloma will be required.\n\n2\\. Patients with relapsed\u002Frefractory multiple myeloma with at least three prior lines of therapy 3. Received an\n\n1. Anti-CD38 antibody\n2. Immunomodulatory agent (IMiD)\n3. Proteasome inhibitor (PI) 4. Currently has MM with measurable disease, defined as:\n\n   * a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g\u002FdL and\u002For urine monoclonal protein levels of at least 200 mg\u002F24 hours\n   * for patients without measurable serum and urine M-protein levels, an involved SFLC \\> 100 mg\u002FL or abnormal SFLC ratio\n   * for patients with IgD MM, a monoclonal immunoglobulin IgD of at least 5500 mg\u002FL or meet other measurable disease eligibility criteria\n   * for patients with IgA MM, total IgA of \\> 700 mg\u002FdL 5. Currently has progressive MM: MM patients that are relapsed or have refractory disease from at least 3 regimens or lines of therapy are eligible for enrollment provided they fulfill the other eligibility criteria:\n   * patients are considered relapsed, when they progress greater than 60 days from their last dose of treatment\n   * patients are refractory when they progress while currently receiving the treatment or within 8 weeks of its last dose 6. Adequate hepatic function within 14 days prior to C1D1: Total bilirubin \\\u003C 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \\\u003C 3 × ULN), and Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to \\\u003C 2 × ULN.\n\n     7\\. Adequate renal function within 14 days prior to C1D1 as determined by OR estimated CrCl of \\> 60 mL\u002Fmin, calculated using the Cockcroft and Gault formula (140 - Age) • Mass (kg)\u002F (72 • creatinine mg\u002FdL); multiply by 0.85 if female (87)(Appendix 5).\n\n     8\\. Adequate hematopoietic function within 14 days prior to C1D1: total WBC count ≥1500\u002Fmm3, ANC ≥1000\u002Fmm3, hemoglobin ≥8.5 g\u002FdL and platelet count ≥75,000\u002Fmm3 (patients for whom \\\u003C50% of BM nucleated cells are plasma cells) or ≥50,000\u002Fmm3 (patients for whom ≥50% of BM nucleated cells are plasma cells).\n\n     9\\. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, G-CSF, GM-CSF, and platelet stimulators (e.g., eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study.\n\n     10\\. Patients must have:\n   * At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the start of study treatment\n   * At least a 1-week interval from the last platelet transfusion prior to the start of study treatment\n   * However, patients may receive RBC and\u002For platelet transfusions as clinically indicated per institutional guidelines during the study 11. Female patients of childbearing potential (FCBP) must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active must use highly effective methods of contraception throughout the study and for one month following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period. Specifically:\n   * FCBP† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU\u002FmL within 10 - 14 days prior to and again within 24 hours of starting treatment and must either commit to continued abstinence from heterosexual intercourse or use acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, and at least 28 days before she starts therapy. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.\n\n     † A FCBP (female of childbearing potential) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) 12. Able to take antiplatelet therapy if platelet count is above 30 x 109\u002FL. Options include aspirin (acetylsalicylic acid, ASA) at 81 or 325\u002Fmg\u002Fdaily, warfarin low molecular weight hepairin, Pradaza, Eliquis, or Xarelto.\n\n     13\\. Patients with history of human immunodeficiency virus (HIV) are eligible if they have CD4+ T cell counts ≥350 cells\u002FµL, negative viral load per institutional standard, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.\n\n     14\\. Patients with untreated hepatitis C virus (HCV) are eligible if there is a documentation of negative viral load per institutional standard.\n\n     15\\. Age ≥ 18 years of age. 16. Willing and able to provide written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.\n\n     17\\. Able to adhere to the study visit schedule and other protocol requirements.\n\nExclusion Criteria:\n\nPatients meeting any of the following exclusion criteria are not eligible to enroll in this study:\n\n1. Patients who had prior exposure to ruxolitinib or selinexor\n2. Prior malignancy that required treatment or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 3 years prior to randomization. Cancer treated with curative intent for \\>5 years previously and without evidence of recurrence will be allowed.\n3. Have light chain amyloidosis\n4. Have plasma cell leukemia\n5. Have history of active tuberculosis\n6. Have any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, POEMS syndrome \\[polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes\\], primary amyloidosis, etc.) that is likely to interfere with study procedures.\n7. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.\n8. Received the following prior therapy:\n\n   * Chemotherapy within 3 weeks of study drugs\n   * Corticosteroids (\\>20 mg\u002Fdaily prednisone or equivalent) within 3 weeks of study drugs to ensure that steroid dose intensity at the beginning of the treatment is not altered by administration of steroids prior to the study. Consumption of steroids within 3 weeks of the treatment may interfere with efficacy and side effects due to differences of steroid intensity.\n   * Immunotherapy, immunomodulatory drugs, or proteasome inhibitors within 3 weeks before administration of study drugs\n   * Extensive radiation therapy within 28 days before study drugs. Receipt of localized radiation therapy does not preclude enrollment.\n   * Use of any other experimental drug or therapy within 28 days of study drugs\n   * Strong CYP3A4 inhibitors, strong CYP3A4 inducers and fluconazole doses \\>200 mg daily within 5 half-lives before study drugs. (For example, clarithromycin has half-life of 4 hours so washout period for clarithromycin is 20 hours.)\n9. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.\n10. Known hypersensitivity to compounds of similar chemical or biological composition to ruxolitinib or steroids.\n11. Concurrent use of other anti-cancer agents or treatments.\n12. Severe hypercalcemia, i.e., serum calcium ≥ 12 mg\u002FdL (3.0 mmol\u002FL) corrected for albumin\n13. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he\u002Fshe were to participate in the study or confounds the ability to interpret data from the study.\n14. Pregnant or breastfeeding females.\n15. Body surface area (BSA) \\\u003C1.4 m2 at baseline, calculated by the Dubois or Mosteller method.\n16. Life expectancy of less than 3 months.\n17. Major surgery within 4 weeks prior to C1D1.\n18. Active, unstable cardiovascular function, as indicated by the presence of:\n\n    1. Symptomatic ischemia, or\n    2. Uncontrolled clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmic are excluded; patients with first degree atrioventricular block or asymptomatic left anterior fascicular block\u002Fright bundle branch block will not be excluded), or\n    3. CHF of New York Heart Association Class ≥3 or known left ventricular ejection fraction \\\u003C 40%, or\n    4. Myocardial infarction (MI) within 3 months prior to C1D1 or\n    5. Stroke and other thrombosis, such as, pulmonary embolism (PE) or deep vein thrombosis (DVT) within 3 months prior to C1D1.\n19. Any active GI dysfunction interfering with the patient's ability to swallow tablets, or any active GI dysfunction that could interfere with absorption of study treatment.\n20. Inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (CPGO) (NCCN CPGO) for antiemesis and anorexia\u002Fcachexia (palliative care).\n21. Any active, serious psychiatric, medical, or other conditions\u002Fsituations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.\n22. Contraindication to any of the required concomitant drugs or supportive treatments.\n23. Patients unwilling or unable to comply with the protocol.","ALL",{"count":19,"type":20},30,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","Selinexor, a first-in-class, oral selective exportin 1 (XPO1) inhibitor, has shown promise in pre-clinical and clinical studies. It functions by inhibiting the nuclear export protein XPO1, resulting in the accumulation of tumor suppressor proteins and inhibition of oncoprotein mRNAs, which is selectively lethal to myeloma cells. Selinexor has demonstrated activity in combination with various drugs, including glucocorticoids and proteasome inhibitors, leading to its FDA approval for the treatment of relapsed or refractory multiple myeloma.",[26,27],"Multiple Myeloma in Relapse","Multiple Myeloma, Refractory",[29,27,26],"Multiple Myeloma","RECRUITING","2025-01-14",{"date":33,"type":34},"2025-01-16","ACTUAL",{"date":36,"type":34},"2024-08-06",{"date":38,"type":20},"2027-05-01",{"name":40,"class":41},"Oncotherapeutics","INDUSTRY",1,{"id":44,"slug":45,"hasResults":11,"nctId":46,"briefTitle":47,"officialTitle":48,"acronym":4,"eligibilityCriteria":49,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":50,"targetDuration":4,"studyType":21,"phases":52,"briefSummary":54,"conditions":55,"keywords":56,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":60,"startDateStruct":61,"completionDateStruct":63,"leadSponsor":65,"locationsCount":66},"100524930","phase-2-a-study-of-venetoclax-in-combination-with-isatuximab-and-dexamethasone-for-relapsedrefractory-multiple-myeloma-100524930","NCT06115135","A Study of Venetoclax in Combination With Isatuximab and Dexamethasone for Relapsed\u002FRefractory Multiple Myeloma","A Phase 2 Study of Venetoclax in Combination With Isatuximab and Dexamethasone for Relapsed\u002FRefractory Multiple Myeloma Patients With t(11;14)","Inclusion Criteria:\n\nSubjects must meet all the following inclusion criteria to be eligible to enroll in this study.\n\n1.Has a diagnosis of MM based on standard criteria as follows: Myeloma Criteria: Must be At least 1 of 2\n\n1. Clonal bone marrow plasma cells \\>10%\n2. Biopsy-proven bony or extramedullary plasmacytoma\n\nActive Myeloma criteria: Must Meet At Least ONE of the Following:\n\nMeet at least one of the sub-criteria for #1 Evidence of End Organ Damage (a, b, c, or d), OR Meet sub-criteria #2. 60% or greater bone marrow plasma cells, OR Meet sub-criteria #3 Serum free light chain ratio, OR Meet sub-criteria #4 More than one focal lesion on MRI \\> 5mm in size.\n\n1. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically\n\n   1. Hypercalcemia: serum calcium \\>0.25 mmol\u002FL (\\>1mg\u002FdL) higher than the upper limit of normal or \\>2.75 mmol\u002FL (\\>11mg\u002FdL)\n   2. Renal insufficiency: creatinine clearance \\\u003C40 mL per minute or serum creatinine \\>177mol\u002FL (\\>2mg\u002FdL)\n   3. Anemia: hemoglobin value of \\>20g\u002FL below the lowest limit of normal, or a hemoglobin value \\\u003C100g\u002FL\n   4. Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET\u002FCT. If bone marrow has \\\u003C10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement\n2. 60% or greater clonal plasma cells on bone marrow examination\n3. Serum involved \u002F uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved light chain is at least 100 mg\u002FL (a patient's involved free light chain either kappa or lambda is the one that is above the normal reference range; the uninvolved free light chain is the one that is typically in, or below, the normal range)\n4. More than one focal lesion on MRI that is at least 5mm or greater in size The patient must have met the criteria for Active Myeloma at some stage following the diagnosis of Myeloma. Source documentation for both Myeloma and Active Myeloma will be required.\n\n2\\. Currently has MM with measurable disease, defined as:\n\n1. a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g\u002FdL and\u002For urine monoclonal protein levels of at least 200 mg\u002F24 hours\n2. for patients without measurable serum and urine M-protein levels, an involved SFLC \\> 100 mg\u002FL or abnormal SFLC ratio\n3. for patients with IgD MM, a monoclonal immunoglobulin IgD of at least 1500 mg\u002FL or meet other measurable disease eligibility criteria\n\n   3\\. Show the (11;14), as demonstrated by FISH or cytogenetic analysis at screening or at any point prior to screening. If performed more than 45 days prior, it should be repeated at the investigator's discretion.\n\n   4\\. Absolute neutrophil count ≥ 1.5 x 109\u002FL 5. Platelet count ≥ 75 x 109\u002FL 6. Hemoglobin ≥ 8.0 g\u002FdL within 21 days prior to enrollment. 7. Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL\u002Fminute as calculated by Cockcroft-Gault method 8. Total bilirubin levels ≤ 2.0 mg\u002FdL (normal levels) 9. AST (SGOT) and ALT (SGPT) ≤ 2 x ULN 10. Serum potassium 3.0-5.5 mEq\u002FL 11. Female of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU\u002FmL within 10 - 14 days prior to and again within 24 hours of starting and must either commit to continued abstinence from heterosexual intercourse or use acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, and at least 28 days before she starts taking treatment drugs. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Contraception measures should be continued for 3 months following the treatment completion.\n\n   †A FCBP (female of childbearing potential) is a sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months 12. Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 2 13. Participant must have received at least 1 prior line of therapy for multiple myeloma, including a proteasome inhibitor, lenalidomide, and glucocorticosteroids but not necessarily in one treatment regimen 14. Participant currently has documented progressive MM per IMWG criteria\n\nExclusion Criteria:\n\nSubjects meeting any of the following exclusion criteria are not to be enrolled in the study:\n\n1. Participant has a history of intolerability to any of the study drugs\n2. Participant has any of the following conditions: amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), known human immunodeficiency viral (HIV) infection, active hepatitis B or C infection based on blood screen tests, significant cardiovascular disease, including uncontrolled angina, severe or uncontrolled arrhythmia, recent myocardial infarction within 6 months of screening, or congestive heart failure New York Heart Association (NYHA) Class greater than or equal to 3, Major surgery within 4 weeks prior to screening, acute infections requiring parenteral therapy (antibiotic, antifungal, or antiviral) within 14 days prior to screening, uncontrolled diabetes or uncontrolled hypertension within 14 days prior to screening, any other medical condition that, in the opinion of the Investigator, would adversely affect the participant's participation in the study\n3. Participant has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions: previous malignancy with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study\n4. If participant had prior allogeneic stem cell transplant (SCT), participant has evidence of ongoing graft-versus-host disease (GvHD)\n5. Participants that are pregnant or breast feeding\n6. Participants with hypersensitivity to any study medications and\u002For their excipients\n7. Treatment with an anti-CD38 antibody (daratumumab or isatuximab) within the last 3 weeks\n8. For those patients treated with an anti-CD38 antibody (daratumumab or isatuximab), alone or in combination, without achieving a best response of at least MR\n9. Treatment with venetoclax\n10. Treatment with any of the following prior to the first dose of study drug:\n\n    1. Chemotherapy within 3 weeks of starting study drugs\n    2. Corticosteroids (\\>20 mg per day prednisone or equivalent) within 3 weeks of starting study drugs\n    3. Immunotherapy, antibody therapy, immunomodulatory agents, or proteasome inhibitors within 3 weeks of starting study drugs\n    4. Extensive radiation therapy within 28 days of starting study drugs. Receipt of localized radiation therapy does not preclude enrollment\n    5. Use of any other experimental drug or therapy within 28 days of starting study drugs\n    6. Moderate or strong cytochrome P450 3A (CYP3A) inhibitors or inducers within 7 days of starting study drugs\n11. Administration or consumption of any of the following within 3 days prior to the first dose of study drug:\n\n    1. Grapefruit or grapefruit products\n    2. Seville oranges (including marmalade containing Seville oranges)\n    3. Star fruit\n12. Additional prior and concomitant therapy excluded and cautionary medications:\n\n    a. Excluded: i. Anticancer therapies including chemotherapy, radiotherapy, or other investigational therapy, including targeted small molecule agents: Excluded 5 half-lives prior to first dose and throughout venetoclax administration ii. Biologic agents (e.g., monoclonal antibodies) for anti-neoplastic intent: Excluded 21 days prior to first dose and throughout venetoclax administration\n13. Cautionary during the study:\n\n    1. Strong and Moderate CYP3A inhibitors: Exclude during ramp-up phase and consider alternative medications. If the subject requires use of these medications at the cohort designated dose, use with caution and reduce the venetoclax dose by 50% for moderate inhibitors and at least 75% for strong inhibitors during co-administration. After discontinuation of CYP3A inhibitor, wait for 2 to 3 days before venetoclax dose is increased back to the initial maintenance\u002Ftarget dose.\n    2. Strong and Moderate CYP3A inducers: Exclude during ramp-up phase and consider alternative medications. If the subject requires use of these medications at the cohort designated dose, use with caution and contact medical monitor for guidance.\n    3. Additional: Warfarin, P-gp substrates, BCRP substrates, OATP1B1\u002F1B3 substrates, P-gp inhibitors, BCRP inhibitors",{"count":51,"type":20},39,[53],"PHASE2","A phase 2 study of venetoclax in combination with isatuximab and dexamethasone for relapsed\u002Frefractory multiple myeloma patients with t(11;14)",[26,27],[29,57,58,59],"MM","RRMM","Relapsed\u002FRefractory Multiple Myeloma",{"date":33,"type":34},{"date":62,"type":34},"2024-06-20",{"date":64,"type":20},"2027-12-31",{"name":40,"class":41},2,{"id":68,"slug":69,"hasResults":11,"nctId":70,"briefTitle":71,"officialTitle":72,"acronym":4,"eligibilityCriteria":73,"healthyVolunteers":11,"sex":17,"minAge":74,"maxAge":4,"enrollmentInfo":75,"targetDuration":4,"studyType":21,"phases":76,"briefSummary":78,"conditions":79,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":80,"lastUpdatePostDateStruct":81,"startDateStruct":83,"completionDateStruct":85,"leadSponsor":87,"locationsCount":42},"100532192","early-phase-1-pilot-study-using-changes-in-serum-bcma-to-determine-disease-progression-in-multiple-myeloma-100532192","NCT06209606","Pilot Study Using Changes in Serum BCMA to Determine Disease Progression in Multiple Myeloma","Treatment of Patients with Relapsed\u002FRefractory Multiple Myeloma with Ruxolitinib, Methylprednisolone and Lenalidomide: Using Changes in Serum B-Cell Maturation Antigen (BCMA) or International Multiple Working Group (IMWG) Criteria to Determine Disease Progression in Order to Add Lenalidomide to Those Failing the Ruxolitinib\u002FMethylprednisolone Combination","Inclusion Criteria:\n\n* Subjects must meet all the following inclusion criteria to be eligible to enroll in this study.\n\n  1. Has a diagnosis of MM based on standard criteria as follows:\n\n     Major criteria:\n\n  \u003C!-- -->\n\n  1. Plasmacytomas on tissue biopsy\n  2. BM plasmacytosis (greater than 30% plasma cells)\n  3. Monoclonal immunoglobulin spike on serum electrophoresis IgG greater than 3.5 g\u002FdL or IgA greater than 2.0 g\u002FdL or kappa or lambda light chain excretion greater than 1 g\u002Fday on 24-hour urine protein electrophoresis\n\n     Minor criteria:\n\n  \u003C!-- -->\n\n  1. BM plasmacytosis (10% to 30% plasma cells)\n  2. Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria\n  3. Lytic bone lesions\n  4. Normal IgM less than 50 mg\u002FdL, IgA less than 100 mg\u002FdL, or IgG less than 600 mg\u002FdL\n\nAny of the following sets of criteria will confirm the diagnosis of multiple myeloma:\n\n* any 2 of the major criteria\n* major criterion 1 plus minor criterion 2, 3, or 4\n* major criterion 3 plus minor criterion 1 or 3\n* minor criteria 1, 2, and 3, or 1, 2, and 4\n\n  2\\. Currently has MM with measurable disease, defined as:\n* a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g\u002FdL and\u002For urine monoclonal protein levels of at least 200 mg\u002F24 hours\n* for patients without measurable serum and urine M-protein levels, an involved SFLC \\> 100 mg\u002FL or abnormal SFLC ratio\n* for patients with IgD MM, a monoclonal immunoglobulin IgD of at least 5500 mg\u002FL or meet other measurable disease eligibility criteria\n\n  3\\. Currently has progressive MM and has received at least 2 prior regimens including lenalidomide, a proteasome inhibitor, and an anti-CD38 antibody:\n* Patients are considered relapsed when they progress greater than 8 weeks from their last dose of treatment\n* Patients are refractory when they progress while currently receiving the treatment or within 8 weeks of its last dose\n\n  4\\. Ruxolitinib naïve\n\n  5\\. Understand and voluntarily sign an informed consent form before receiving any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn at any time without prejudice to their future medical care\n\n  6\\. Able to adhere to the study visit schedule and other protocol requirements\n\n  7\\. ECOG performance status of ≤ 2 at study entry\n\n  8\\. Life-expectancy of greater than 3 months\n\n  9\\. Laboratory test results within these ranges at Screening and confirmed at enrollment prior to drug dosing on Cycle 1, Day 1:\n* Absolute neutrophil count ≥ 1.5 x 109\u002FL\n\n  o If the bone marrow is extensively infiltrated (≥ 70% plasma cells) then ≥ 1.0 x 109\u002FL\n* Platelet count ≥ 75 x 109\u002FL\n\n  o Patients must not have received platelet transfusion for at least 7 days prior to receiving screening platelet count\n  * If the bone marrow is extensively infiltrated (≥ 70% plasma cells) then ≥ 50 x 109\u002FL\n  * If patient have creatinine clearance of less than 60mL\u002Fmin, patient's platelet count must be greater than 150 x 109\u002FL\n* Hemoglobin ≥ 8.0 g\u002FdL within 21 days prior to enrollment\n\n  o Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed; however, most recent RBC transfusion must have been at least 7 days prior to obtaining screening hemoglobin.\n* Calculated or measured CrCl \\> 60 mL\u002Fminute per Cockcroft-Gault (Appendix 3)\n* Total bilirubin levels ≤ 2.0 mg\u002FdL\n* AST (SGOT) and ALT (SGPT) ≤ 2 x ULN\n* Serum potassium 3.0 - 5.5 mEq\u002FL\n\n  10\\. Patients receiving lenalidomide (Part 2 of the study) must be registered into the mandatory REVLIMID REMS™ program, and be willing and able to comply with the requirements of the REVLIMID REMS™ program\n\n  11\\. FCBP† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU\u002FmL within 10 - 14 days prior to and again within 24 hours of starting ruxolitinib + methylprednisolone and must either commit to continued abstinence from heterosexual intercourse or use acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, and at least 28 days before she starts taking ruxolitinib with or without lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.\n\n  †A FCBP (female of childbearing potential) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; and 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)\n\n  12\\. Able to take antiplatelet therapy if platelet count is above 30 x 109\u002FL. Options include aspirin (acetylsalicylic acid, ASA) at 81 or 325 mg\u002Fdaily and warfarin or low molecular weight heparin if ASA-intolerant\n\nExclusion Criteria:\n\n* Subjects meeting any of the following exclusion criteria are not to be enrolled in the study:\n\n  1. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)\n  2. Plasma cell leukemia (\\> 2.0 × 109\u002FL circulating plasma cells by standard differential)\n  3. Primary amyloidosis\n  4. Non-hematologic malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas\n  5. Patients with uncontrolled infections\n  6. Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\n\n     * Myocardial infarction within 6 months prior to enrollment\n     * New York Heart Association (NYHA) Class II or greater heart failure or uncontrolled angina\n     * Clinically significant pericardial disease\n     * Severe uncontrolled ventricular arrhythmias\n     * Echocardiogram or MUGA evidence of LVEF below institutional normal within 28 days prior to enrollment\n     * Electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening must be documented by the investigator as not medically relevant.\n     * Severe hypercalcemia, i.e., serum calcium ≥ 12 mg\u002FdL (3.0 mmol\u002FL) corrected for albumin\n  7. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form\n  8. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he\u002Fshe were to participate in the study or confounds the ability to interpret data from the study\n  9. Undergone major surgery within 28 days prior enrollment or has not recovered from side effects of such therapy (vertebroplasty or kyphoplasty is not considered to be a major surgery; however, the investigator is to discuss enrollment of a subject with a recent history of kyphoplasty with the medical monitor).\n  10. Pregnant or breastfeeding females (lactating females must agree not to breast feed while taking lenalidomide)\n  11. Received the following prior therapy:\n\n      * Chemotherapy within 3 weeks of study drugs\n      * Corticosteroids (\\>20 mg\u002Fdaily prednisone or equivalent) within 3 weeks of study drugs to ensure that steroid dose intensity at the beginning of the treatment is not altered by administration of steroids prior to the study. Consumption of steroids within 3 weeks of the treatment may interfere with efficacy and side effects due to differences of steroid intensity.\n      * Immunotherapy, antibody therapy, immunomodulatory drugs, or proteasome inhibitors within 3 weeks of study drugs\n      * Extensive radiation therapy within 28 days before study drugs. Receipt of localized radiation therapy does not preclude enrollment.\n      * Use of any other experimental drug or therapy within 28 days of study drugs\n      * JAK inhibitor including ruxolitinib\n  12. Strong CYP3A4 inhibitors, strong CYP3A4 inducers and fluconazole doses \\>200 mg daily within 5 half-lives before study drugs. (For example, clarithromycin has half-life of 4 hours so washout period for clarithromycin is 20 hours.)\n  13. Known hypersensitivity to compounds of similar chemical or biological composition to thalidomide and lenalidomide or steroids.\n  14. Concurrent use of other anti-cancer agents or treatments\n  15. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs\n  16. Known positivity for human immunodeficiency virus (HIV), hepatitis B or C, and \u002For active tuberculosis (TB) including subjects with latent TB or with the risk factor for activation of latent TB.","18 Years",{"count":19,"type":20},[77],"EARLY_PHASE1","This is a phase 1, multicenter, open-label study evaluating the safety and efficacy of ruxolitinib, steroids and lenalidomide among MM patients who currently show progressive disease using BCMA to test progression.",[29],"2024-12-12",{"date":82,"type":34},"2024-12-17",{"date":84,"type":34},"2022-12-08",{"date":86,"type":20},"2029-02",{"name":40,"class":41},{"id":89,"slug":90,"hasResults":11,"nctId":91,"briefTitle":92,"officialTitle":92,"acronym":4,"eligibilityCriteria":93,"healthyVolunteers":11,"sex":17,"minAge":74,"maxAge":4,"enrollmentInfo":94,"targetDuration":4,"studyType":21,"phases":96,"briefSummary":97,"conditions":98,"keywords":99,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":103,"lastUpdatePostDateStruct":104,"startDateStruct":106,"completionDateStruct":108,"leadSponsor":110,"locationsCount":111},"100294278","phase-1-a-phase-1-study-of-ruxolitinib-steroids-and-lenalidomide-for-relapsedrefractory-multiple-myeloma-rrmm-patients-100294278","NCT03110822","A Phase 1 Study of Ruxolitinib, Steroids and Lenalidomide for Relapsed\u002FRefractory Multiple Myeloma (RRMM) Patients","Inclusion Criteria:\n\nSubjects must meet all of the following inclusion criteria to be eligible to enroll in this study.\n\n1\\. Has a diagnosis of MM based on standard criteria as follows:\n\nMajor criteria:\n\n1. Plasmacytomas on tissue biopsy.\n2. Bone marrow plasmacytosis (greater than 30% plasma cells).\n3. Monoclonal immunoglobulin spike on serum electrophoresis IgG greater than 3.5 g\u002FdL or IgA greater than 2.0 g\u002FdL or kappa or lambda light chain excretion greater than 1 g\u002Fday on 24 hour urine protein electrophoresis.\n\nMinor criteria:\n\n1. bone marrow plasmacytosis (10% to 30% plasma cells)\n2. monoclonal immunoglobulin present but of lesser magnitude than given under major criteria\n3. lytic bone lesions\n4. normal IgM less than 50 mg\u002FdL, IgA less than 100 mg\u002FdL, or IgG less than 600 mg\u002FdL\n\nAny of the following sets of criteria will confirm the diagnosis of multiple myeloma:\n\n* any 2 of the major criteria\n* major criterion 1 plus minor criterion 2, 3, or 4\n* major criterion 3 plus minor criterion 1 or 3\n* minor criteria 1, 2, and 3, or 1, 2, and 4\n\n  2\\. Currently has MM with measurable disease, defined as:\n* a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g\u002FdL and\u002For\n* urine monoclonal protein levels of at least 200mg\u002F24 hours\n* for patients without measurable serum and urine M-protein levels, an involved SFLC \\> 100 mg\u002FL or abnormal SFLC ratio\n* for patients with IgD MM, a monoclonal immunoglobulin IgD of at least 1500 mg\u002FL or meet other measurable disease eligibility criteria\n\n  3\\. Currently has progressive MM\n\nMM patients that are relapsed or have refractory disease from at least 2 regimens or lines of therapy including an IMID and a proteasome inhibitor, are eligible for enrollment provided they fulfill the other eligibility criteria:\n\n* Patients are considered relapsed, when they progress greater than 8 weeks from their last dose of treatment.\n* Patients are refractory when they progress while currently receiving the treatment or within 8 weeks of its last dose.\n\n  4\\. Previous exposure to lenalidomide independent of the response\n\n  5\\. The patient is not a candidate for a transplant\n\n  6\\. Understand and voluntarily sign an informed consent form before receiving any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn at any time without prejudice to their future medical care.\n\n  7\\. Able to adhere to the study visit schedule and other protocol requirements\n\n  8\\. ECOG performance status of ≤ 2 at study entry\n\n  9\\. Life-expectancy of greater than 3 months\n\n  10\\. Laboratory test results within these ranges at Screening and confirmed at enrollment prior to drug dosing on Cycle 1, Day 1:\n* Absolute neutrophil count ≥ 1.5 x 10E9\u002FL; if the bone marrow is extensively infiltrated ( ≥ 70% plasma cells) then ≥ 1.0 x 10E9\u002FL\n* Platelet count ≥ 75 x 10E9\u002FL; if the bone marrow is extensively infiltrated ( ≥ 70% plasma cells) then ≥ 50 x 10E9\u002FL patients must not have received platelet transfusion for at least 7 days prior to receiving screening platelet count. If patient have creatinine clearance of less than 60mL\u002Fmin, patient's platelet count must be greater than 150 x 10E9\u002FL.\n* Hemoglobin ≥ 8.0 g\u002FdL within 21 days prior to enrollment. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed; however, most recent RBC transfusion must have been at least 7 days prior to obtaining screening hemoglobin.\n* Calculated or measured creatinine clearance (CrCl) of \\> 60 mL\u002Fminute (Study Part 1,2,3(2), and 4) or 30 to ≤ 60 mL\u002Fminute (Part 3(1)) as calculated by Cockcroft-Gault method (Appendix 3).\n* Total bilirubin levels ≤ 2.0 mg\u002FdL (normal levels)\n* AST (SGOT) and ALT (SGPT) ≤ 2 x ULN\n* Serum potassium 3.0 - 5.5 mEq\u002FL\n\n  11\\. Patients must be registered into the mandatory REVLIMID REMS™ program, and be willing and able to comply with the requirements of the REVLIMID REMS™ program\n\n  12\\. FCBP† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU\u002FmL within 10 - 14 days prior to and again within 24 hours of starting ruxolitinib and must either commit to continued abstinence from heterosexual intercourse or use acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, and at least 28 days before she starts taking ruxolitinib with or without lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.\n\n  † A FCBP (female of childbearing potential) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)\n\n  13\\. Able to take aspirin (acetylsalicylic acid, ASA) at 81 or 325 mg\u002Fdaily as antiplatelet therapy if platelet count is above 30 x 10E9\u002FL (subjects intolerant to ASA may use warfarin or low molecular weight heparin)\n\nExclusion Criteria:\n\n* Subjects meeting any of the following exclusion criteria are not to be enrolled in the study:\n\n  1. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)\n  2. Plasma cell leukemia (\\> 2.0 × 10E9\u002FL circulating plasma cells by standard differential)\n  3. Primary amyloidosis\n  4. Non-hematologic malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas\n  5. Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:\n\n     * Myocardial infarction within 6 months prior to enrollment\n     * New York Heart Association (NYHA) Class II or greater heart failure or uncontrolled angina\n     * Clinically significant pericardial disease\n     * Severe uncontrolled ventricular arrhythmias\n     * Echocardiogram or MUGA evidence of LVEF below institutional normal within 28 days prior to enrollment\n     * Electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.\n  6. Severe hypercalcemia, i.e., serum calcium ≥ 12 mg\u002FdL (3.0 mmol\u002FL) corrected for albumin\n  7. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form\n  8. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he\u002Fshe were to participate in the study or confounds the ability to interpret data from the study\n  9. Undergone major surgery within 28 days prior enrollment or has not recovered from side effects of such therapy (vertebroplasty or kyphoplasty is not considered to be a major surgery; however, the investigator is to discuss enrollment of a subject with a recent history of kyphoplasty with the medical monitor).\n  10. Pregnant or breast feeding females (lactating females must agree not to breast feed while taking lenalidomide)\n  11. Received the following prior therapy:\n\n      * Chemotherapy within 3 weeks of study drugs\n      * Corticosteroids (\\>20 mg\u002Fdaily prednisone or equivalent) within 3 weeks of study drugs to ensure that steroid dose intensity at the beginning of the treatment is not altered by administration of steroids prior to the study. Consumption of steroids within 3 weeks of the treatment may interfere with efficacy and side effects due to differences of steroid intensity.\n      * Immunotherapy or antibody therapy as well as thalidomide, arsenic trioxide, or bortezomib within 21 days before study drugs\n      * Lenalidomide within 7 days before study drugs\n      * Lenalidomide within 21 days before study drugs (Part 4 only)\n      * Extensive radiation therapy within 28 days before study drugs. Receipt of localized radiation therapy does not preclude enrollment.\n      * Use of any other experimental drug or therapy within 28 days of study drugs\n      * Strong CYP3A4 inhibitors, strong CYP3A4 inducers and fluconazole doses \\>200 mg daily within 5 half-lives before study drugs. (For example, clarithromycin has half-life of 4 hours so washout period for clarithromycin is 20 hours.)\n  12. Known hypersensitivity to compounds of similar chemical or biological composition to thalidomide and lenalidomide or steroids.\n  13. Concurrent use of other anti-cancer agents or treatments\n  14. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs\n  15. Known positivity for human immunodeficiency virus (HIV), hepatitis B or C, and \u002For active tuberculosis (TB) including subjects with latent TB or with the risk factor for activation of latent TB.",{"count":95,"type":20},134,[23],"This is a phase 1, multicenter, open-label study evaluating the safety and efficacy of ruxolitinib, steroids and lenalidomide among MM patients who currently show progressive disease.",[29],[100,101,102,59],"Ruxolitinib","Steroids","Lenalidomide","2023-10-30",{"date":105,"type":34},"2023-11-01",{"date":107,"type":34},"2017-02-01",{"date":109,"type":20},"2027-02",{"name":40,"class":41},13,""]