[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"paraproteinemias\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:paraproteinemias":34},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,59,89,121,147],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":41,"overallStatus":46,"whyStopped":4,"lastUpdateSubmitDate":47,"lastUpdatePostDateStruct":48,"startDateStruct":51,"completionDateStruct":53,"leadSponsor":55,"locationsCount":58},"100598722","phase-1-a-study-to-evaluate-a-novel-gene-therapy-in-patients-with-relapsed-and-refractory-multiple-myeloma-100598722",false,"NCT07075185","A Study to Evaluate a Novel Gene Therapy in Patients With Relapsed and Refractory Multiple Myeloma","A Phase 1 Study to Evaluate the Safety of KLN-1010, a Novel, In Vivo Gene Therapy to Generate Anti-B Cell Maturation Antigen (Anti-BCMA) Chimeric Antigen Receptor-T Cells (CAR-T) in Patients With Relapsed and Refractory Multiple Myeloma","inMMyCAR","Inclusion Criteria:\n\n* Participants must have relapsed and refractory multiple myeloma (RRMM) with measurable disease\n* Participants must have received at least 3 prior lines of therapy including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and CD38-directed monoclonal antibody\n* Participants must have an Eastern Cooperative Group (ECOG) performance status of 0-1\n* Participants must have acceptable laboratory values as defined by the protocol\n\nExclusion Criteria:\n\n* Participants must not have known central nervous system (CNS) involvement with myeloma\n* Participants cannot have plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, or primary light chain amyloidosis\n* Participants cannot have ongoing acute systemic infection requiring antimicrobial therapy\n* Participants cannot require systemic steroids for any condition","ALL","18 Years",{"count":20,"type":21},70,"ESTIMATED","INTERVENTIONAL",[24],"PHASE1","The goal of this clinical trial is to evaluate the safety, tolerability, and recommended Phase 2 Dose (RP2D) of KLN-1010 in patients with relapsed or refractory multiple myeloma.",[27,28,29,30,31,32,33,34,35,36,37,38,39,40],"Multiple Myeloma in Relapse","Myeloma Multiple","Multiple Myeloma Progression","Neoplasms by Histologic Type","Neoplasm","Hemostatic Disorders","Vascular Disorder","Paraproteinemias","Blood Protein Disorders","Hematologic Disease and Disorders","Lymphoproliferative Disorders","Immunoproliferative Disorders","Immune System Disease","Gene Therapy",[42,43,44,45],"in vivo CAR-T","multiple myeloma","gene therapy","BMCA","RECRUITING","2026-04-22",{"date":49,"type":50},"2026-04-24","ACTUAL",{"date":52,"type":50},"2025-07-16",{"date":54,"type":21},"2042-05",{"name":56,"class":57},"Kelonia Therapeutics, Inc.","INDUSTRY",7,{"id":60,"slug":61,"hasResults":11,"nctId":62,"briefTitle":63,"officialTitle":64,"acronym":65,"eligibilityCriteria":66,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":67,"targetDuration":4,"studyType":22,"phases":69,"briefSummary":71,"conditions":72,"keywords":75,"overallStatus":46,"whyStopped":4,"lastUpdateSubmitDate":78,"lastUpdatePostDateStruct":79,"startDateStruct":81,"completionDateStruct":83,"leadSponsor":85,"locationsCount":88},"100584485","phase-2-the-effect-of-daratumumab-in-patients-with-monoclonal-gammopathy-of-renal-significance-mgrs-in-finland-100584485","NCT06889948","The Effect of Daratumumab in Patients with Monoclonal Gammopathy of Renal Significance (MGRS) in Finland","Daratumumab in Monoclonal Gammopathy of Renal Significance in Finland","DAMOCLES","Inclusion Criteria:\n\n1. Males or females ≥ 18 years of age\n2. Subject has provided informed consent prior to initiation of the study or subject's legally acceptable representative has provided informed consent prior to the study when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.\n3. Renal biopsy confirmed MGRS-disease\n\n   * Renal biopsy must not be older than 3 months before informed consent. However, if renal biopsy is older than 3 mo and the study team is convinced that major histological changes have not occurred, a biopsy older than that can exceptionally be accepted.\n   * Renal transplant patients are allowed\n4. Amount of proteinuria ≥ 500 mg\u002F24 h OR eGFR ≥ 20 ml\u002Fmin prior to the study\n5. Previous anticlonal treatment is allowed if deemed ineffective\n\nExclusion Criteria:\n\n1. Myeloma or systemic AL amyloidosis (smoldering myeloma sized plasma cell clone is allowed when in association with a documented MGRS condition and AHL amyloidosis and AH amyloidosis are included)\n2. Cancer that requires treatment,\n3. MGRS related to B-cell malignant disorders,\n4. Known HIV infection, active hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that achieve sustained virologic response (PCR negativity in HBVNh) with antiviral therapy are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on the study),\n5. Pregnancy or breastfeeding,\n6. Cyclophosphamide within 6 months of enrollment, or oral high-dose prednisone or equivalent within 6 weeks of enrollment;\n\n   * prednisone or its equivalent at a dosage of ≤10 mg daily for a condition unrelated to MGRS (e.g. asthma or gout) allowed.\n   * mycophenolate mofetil (MMF), calcineurin inhibitors (CNI) or azathioprine treated patients are eligible if proteinuria is not improving or if kidney function is declining despite treatment with these medications. Once therapy with daratumumab started, these medications need to be discontinued unless they are used as immunosuppressive medication due to renal transplantation.\n7. In patients who previously received rituximab, reconstitution of B cells (CD19 normalized, Ly-B-CD19 lab.code 8329) required.\n8. Inability to use daratumumab and to comply with the study protocol as assessed by treating nephrologist and\u002For hematologist (e.g. severe psychiatric illness, severe lung disease, known allergy to daratumumab)",{"count":68,"type":21},30,[70],"PHASE2","The goal of this clinical trial is to learn if drug daratumumab works to treat kidney diseases other than AL-amyloidosis that fall under the category of monoclonal gammopathy of renal significance (MGRS).\n\nThe main questions it aims to answer are:\n\nDoes daratumumab have an effect on the patients' renal function or the amount of proteinuria?\n\nDoes daratumumab have an effect on the hematological endpoints evaluated by minimal residual disease (MRD) and the difference between involved and uninvolved free light chain (dFLC)?\n\nAlso changes in quality of life (according to EORTC QLQ-C30) and mechanism of complement system activation are evaluated. The number of patiets with partial or very good partial hematological remission and the number of patients with adverse events related to daratumumab are also recorded.",[73,34,74],"Kidney Failure","Glomerulonephritis",[76,77],"Monoclonal gammopathy of renal significance","daratumumab","2025-03-17",{"date":80,"type":50},"2025-03-21",{"date":82,"type":50},"2024-01-19",{"date":84,"type":21},"2027-06",{"name":86,"class":87},"Helsinki University Central Hospital","OTHER",1,{"id":90,"slug":91,"hasResults":11,"nctId":92,"briefTitle":93,"officialTitle":94,"acronym":4,"eligibilityCriteria":95,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":96,"enrollmentInfo":97,"targetDuration":4,"studyType":22,"phases":99,"briefSummary":100,"conditions":101,"keywords":110,"overallStatus":46,"whyStopped":4,"lastUpdateSubmitDate":112,"lastUpdatePostDateStruct":113,"startDateStruct":115,"completionDateStruct":117,"leadSponsor":119,"locationsCount":88},"100536932","phase-1-a-study-to-evaluate-the-safety-pkpd-of-oricar-017-in-subjects-with-rrmm---rigel-study-100536932","NCT06271252","A Study to Evaluate the Safety, PK\u002FPD of (OriCAR-017) in Subjects With RR\u002FMM - RIGEL Study","A Phase I\u002FII, Open-label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Anti-GPRC5D CAR-T Cell Product (OriCAR-017) in Subjects With Relapsed\u002FRefractory Multiple Myeloma.","Inclusion Criteria:\n\nCapable of giving signed informed consent\n\nSubjects aged 18 to 75 years (inclusive) at Screening (signing the ICF).\n\nExpected survival period is \\>12 weeks.\n\nDiagnosis of MM according to the IMWG criteria (2016 version).\n\nOne of the following criteria must be met:\n\nIf immunoglobulin (Ig)G type MM, then serum M protein \\>10 g\u002FL; if IgA, IgD, IgE or IgM type MM, then serum M protein \\>5 g\u002FL\n\nUrine M protein level \\>200 mg\u002F24 hour\n\nIf light chain type MM, then serum free light chain (sFLC) \\>100 mg\u002FL and K\u002Fλ FLC ratio is abnormal.\n\nExtramedullary lesions (\\>1 cm for diameter of the short axis).\n\nFor Phase I (dose-escalation) - Subjects who had received at least 3 prior lines of therapy, had previous exposure to BCMA-Ag+ therapies, and were refractory to the last line of therapy.\n\nFor Phase I (dose-expansion) and Phase II: Subjects with previous exposure to BCMA directed therapies including BCMA bispecific antibody (e.g., teclistamab), BCMA antibody directed conjugate (such as BLENREP), and BCMA-CAR-T (such as CARVYKT1TM)\n\nSubjects with adequate hematologic, renal, hepatic, pulmonary and cardiac function.\n\nSubject and partners willing to take and or use effective contraceptive measures until 2 years post IMP infusion.\n\nExclusion Criteria:\n\nPregnant or breastfeeding.\n\nSeropositive for history of human immunodeficiency virus Active Hepatitis B infection and or Hepatitis C infection\n\nKnown active or prior history of CNS involvement\n\nHistory of autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) caused damage to terminal organs or required systemic application of immunosuppressive or other drugs in the past 2 years\n\nPresence of uncontrolled active infection\n\nSubjects who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks of Screening Visit or who plan to undergo ASCT during the study.\n\nSubjects who received allogeneic stem cell therapy.\n\nAny condition that in the opinion of the Investigator, would interfere with evaluation of the IMP.\n\nReceived Bendamustine treatment 1 year prior to Screening Visit.","75 Years",{"count":98,"type":21},81,[24],"The is a first clinical study for Oricell Therapeutics Inc. in the United States to evaluate the safety, PK, PD and preliminary efficacy of our anti-GPRC5D cell product (OriCAR-017) in subjects with relapsed\u002Frefractory multiple myeloma.\n\nRIGEL Study",[102,30,103,32,104,105,34,35,106,107,37,38,108,109],"Neoplasms, Plasma Cell","Neoplasms","Vascular Diseases","Cardiovascular Diseases","Hematologic Diseases","Hemorrhagic Disorders","Immune System Diseases","Multiple Myeloma",[111],"R\u002FR MM, CAR-T","2024-08-01",{"date":114,"type":50},"2024-08-02",{"date":116,"type":50},"2024-04-03",{"date":118,"type":21},"2028-04-12",{"name":120,"class":57},"OriCell Therapeutics Co., Ltd.",{"id":122,"slug":123,"hasResults":11,"nctId":124,"briefTitle":125,"officialTitle":126,"acronym":4,"eligibilityCriteria":127,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":128,"targetDuration":4,"studyType":22,"phases":130,"briefSummary":131,"conditions":132,"keywords":4,"overallStatus":46,"whyStopped":4,"lastUpdateSubmitDate":137,"lastUpdatePostDateStruct":138,"startDateStruct":140,"completionDateStruct":142,"leadSponsor":144,"locationsCount":146},"100483343","phase-1-a-study-to-investigate-safety-and-clinical-activity-of-belantamab-mafodotin-in-combination-with-lenalidomide-dexamethasone-and-nirogacestat-in-patients-with-transplant-ineligible-newly-diagnosed-multiple-myeloma-100483343","NCT05573802","A Study to Investigate Safety and Clinical Activity of Belantamab Mafodotin in Combination With Lenalidomide, Dexamethasone and Nirogacestat in Patients With Transplant Ineligible Newly Diagnosed Multiple Myeloma","A Phase 1\u002F2, Dose and Schedule Evaluation Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin Administrated in Combination With Lenalidomide, Dexamethasone and Nirogacestat in Patients With Transplant Ineligible Newly Diagnosed Multiple Myeloma","Inclusion Criteria:\n\n1. Participant must be \\>18 years of age\n2. Monoclonal plasma cells in the bone marrow (BM) ≥10% or presence of a biopsy proven plasmacytoma and documented Multiple Myeloma (MM) satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria:\n\n   CRAB criteria:\n\n   i. Hypercalcemia: serum calcium \\>0.25 mmol\u002FL (\\>1 mg\u002FdL) higher than upper limit of normal (ULN) or \\>2.75 mmol\u002FL (\\>11 mg\u002FdL).\n\n   ii. Renal insufficiency: creatinine clearance (CrCI) \\\u003C40mL\u002Fmin or serum creatinine \\>177 μmol\u002FL (\\>2 mg\u002FdL).\n\n   iii. Anemia: hemoglobin \\>2 g\u002FdL below the lower limit of normal or hemoglobin \\\u003C10 g\u002FdL.\n\n   iv. Bone lesions: one or more osteolytic lesions on skeletal radiography, Computed tomography (CT), or Positron emission tomography (PET-CT).\n\n   Biomarkers of Malignancy:\n   1. Clonal BM plasma cell percentage ≥60%.\n   2. Involved: uninvolved serum free light chain (sFLC) ratio ≥100.\n   3. More than 1 focal lesion on magnetic resonance imaging (MRI) studies.\n3. Must have at least ONE aspect of measurable disease, defined as one of the following:\n\n   * Urine M-protein excretion ≥200 mg\u002F24 hrs (≥0.2 g\u002F24 hrs), or\n   * Serum M-protein concentration ≥0.5 g\u002FdL (≥5.0 g\u002FL), or\n   * Serum FLC assay: involved FLC level ≥10 mg\u002FdL (≥100 mg\u002FL) and an abnormal serum FLC ratio (\\\u003C0.26 or \\>1.65).\n4. Not a candidate for high-dose chemotherapy with autologous stem cell transplantation due to presence of significant comorbid condition(s), such as cardiac, pulmonary or other major organ dysfunction that are likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation. The patients will be assessed with the IMWG frailty index, a scoring system based on age, comorbidities, and cognitive and physical conditions, which is recommended by the European Society for Medical Oncology (ESMO) guidelines. Patients with International Myeloma Working Group (IMWG) frailty index score 1 or 2 will be considered transplant ineligible. The reason(s) for transplant ineligibility will be collected in the case report forms (CRFs).\n5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.\n6. Adequate organ system function as defined by the below laboratory assessments. Hematologic\n\n   * Absolute neutrophil count (ANC) ≥1.25 X 10\\^9\u002FL; granulocyte colony-stimulating factor (G-CSF) use for the past 14 days is NOT allowed.\n   * Hemoglobin ≥8.0 g\u002FdL; transfusions are not permitted in the past 14 days prior to the assessment. Erythropoietin use is allowed.\n   * Platelet count ≥50 x 10\\^9\u002FL if the BM is \\>50% involved in myeloma. Otherwise, ≥75 x 10\\^9\u002FL; transfusions or platelet stimulating agents are NOT allowed in the past 14 days prior to the assessment.\n\n   Hepatic\n   * Total bilirubin ≤1.5xULN (isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \\\u003C35%).\n   * ALT ≤ 2.5xULN. Renal\n   * Estimate glomerular filtration rate (eGFR) ≥30 mL\u002Fmin\u002F1.73 m2; calculated using the Modified Diet in Renal Disease (MDRD) formula.\n   * Spot urine (albumin\u002Fcreatinine ratio) \\\u003C500 mg\u002Fg (56 mg\u002Fmmol) OR\n   * Urine Dipstick: Negative trace; if ≥1+ only eligible if confirmed \\\u003C500 mg\u002Fg \\[56 mg\u002Fmmol\\] by albumin\u002Fcreatinine ratio (spot urine from first void).\n7. Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:\n\n   A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:\n   * Is not a woman of childbearing potential (WOCBP) defined as follows:\n   * ≥ 45 years of age and has not had menses for \\> 1 year\n   * Patients who have been amenorrhoeic for \\\u003C 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation\n   * Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.\n\n   OR\n   * Is a WOCBP and using two methods of reliable birth control (one method that is highly effective and one additional effective \\[barrier\\] method), beginning 4 weeks before initiating treatment with lenalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of lenalidomide treatment. WOCBP participants must use one method of reliable birth control that is highly effective for 4 months following discontinuation of belantamab mafodotin. WOCBP must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during treatment, during dose interruptions and for 28-days following the last dose of lenalidomide or 4 months following discontinuation of belantamab mafodotin treatment, whichever is longer.\n\n   A WOCBP must have two negative pregnancy tests before therapy initiation. The first test should be performed within 10-14 days, and the second test within 24 hours before the start of lenalidomide therapy.\n\n   The participant should not receive lenalidomide until the investigator has verified that the results of these pregnancy tests are negative. The investigator should evaluate the effectiveness of the contraceptive method in relation to the first dose of the study treatment. The investigator is responsible for a review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.\n\n   WOCBP is a female who:\n   * has achieved menarche at some time point\n   * has not undergone a hysterectomy or bilateral oophorectomy or\n   * has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).\n8. Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:\n\n   Male participants are eligible to participate if they agree to the following during the intervention period and until 28 days after the last dose of lenalidomide or 6 months after the last dose of belantamab mafodotin, whichever is longer, to allow for clearance of any altered sperm.\n   * Refrain from donating sperm\n\n   PLUS either:\n   * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR\n   * Must agree to use contraception\u002Fbarrier as detailed below:\n\n   Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \\\u003C1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females).\n9. Participants must be able to understand the study procedures and agree to participate in the study by providing written informed consent.\n\nExclusion Criteria:\n\n1. Prior systemic therapy for MM or Smoldering MM.\n\n   * NOTE 1: An emergency course of steroids (defined as not greater than 40 mg of dexamethasone \\[or equivalent\\] per day for a maximum of 4 days \\[i.e., a total of 160 mg\\]) is permitted.\n   * NOTE 2: Focal palliative radiation is permitted before enrollment, provided that: it occurred at least 2 weeks before the first dose of the study drug; the participant has recovered from radiation-related toxicities; and the participant did not require corticosteroid administration (for a longer period than that specified in NOTE 1 above) for radiation-induced AEs.\n2. Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute Common Toxicity Criteria for AEs version 5.\n3. Major surgery within 2 weeks before the first dose of the study drug.\n\n   * NOTE 1: patients who underwent major surgery must be clinically stable to be enrolled in the study.\n   * NOTE 2: major surgery shall be defined based on the Investigator's judgment according to the extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes.\n4. Presence of active renal condition (infection, requirement for dialysis or any other significant condition that could affect the participant's safety). Participants with isolated proteinuria resulting from MM are eligible, provided that they fulfil the other inclusion criteria.\n5. Any serious and\u002For unstable pre-existing medical, psychiatric disorder, or other conditions (including laboratory abnormalities) that could interfere with the participant's safety, obtaining informed consent, or compliance with the study procedures.\n6. Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not explained by reversible coagulopathy.\n7. Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease as per the investigator's assessment).\n8. Participants with previous or concurrent malignancies other than MM are excluded. Exceptions are surgically treated cervical carcinoma in situ or any other malignancy that has been considered medically stable for at least 2 years. The participant must not be receiving active therapy other than hormonal therapy for this disease.\n\n   * NOTE: Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction.\n9. Evidence of cardiovascular risk including any of the following:\n\n   * Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities, second degree (Mobitz Type II), or third degree atrioventricular (AV) block.\n   * History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of screening.\n10. Class III or IV heart failure as defined by the New York Heart Association functional classification system.\n11. Uncontrolled hypertension.\n12. Active infection requiring treatment.\n13. Known HIV infection, unless the participant can meet all of the following criteria:\n\n    * Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load \\\u003C400 copies\u002FmL.\n    * CD4+ T-cell (CD4+) count ≥350 cells\u002FuL.\n    * No history of AIDS-defining opportunistic infections within the last 12 months.\n\n      * NOTE: consideration must be given to ART and prophylactic antimicrobials that may have a drug:drug interaction and\u002For overlapping toxicities with belantamab mafodotin or other combination products as relevant\n14. Seropositivity for hepatitis B (defined by a positive test for hepatitis B surface antigen \\[HBsAg\\]).\n\n    * NOTE 1: Participants with resolved infection (i.e., participants who are positive for antibodies to hepatitis B core antigen \\[antiHBc\\] or antibodies to hepatitis B surface antigen \\[antiHBs\\]) must be screened using real-time polymerase chain reaction (PCR). Those who are PCR positive will be excluded.\n    * NOTE 2: presence of antiHBs indicating previous vaccination will not constitute an exclusion criterion.\n15. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before the first dose of the study treatment unless the participant can meet the following criteria:\n\n    * RNA test negative\n    * Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative hepatitis C virus RNA test after a washout period of at least 4 weeks.\n16. Current corneal epithelial disease except for mild punctate keratopathy.\n\n    * NOTE: Participants with mild punctate keratopathy are allowed. Mild (Grade 1) punctuate keratopathy is characterized by the appearance of only a few, if any, microcyst-like epithelial changes (MECs), as identified in the slit-lamp examination, with a low density (non-confluent), and predominantly (≥80%) located in the periphery of the cornea\n17. Intolerance or contraindications to anti-viral prophylaxis.\n18. Unable to tolerate antithrombotic prophylaxis.\n19. AL amyloidosis (light chain amyloidosis), active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening.\n20. Exhibiting clinical signs of or with known history of meningeal or central nervous system involvement by MM.\n21. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin or any of the components of the study treatment.\n22. Use of an investigational drug within 14 days or 5 half-lives (whichever is shorter) preceding the first dose of study drug.\n23. Plasmapheresis within 7 days before the first dose of the study drug.\n24. Participants with active small and\u002For large intestinal disease which is not adequately controlled with the appropriate treatment (e.g., uncontrolled diarrheal disease).\n25. Participants with uncontrolled skin disease.\n26. Participants with any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement.\n27. Participants with previous administration of a gamma secretase inhibitor.\n28. Participants with concomitant administration of a strong or moderate CYP3A4 inhibitor or inducer.\n29. Any serious and\u002For unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.\n30. Participant must not have received a live or live-attenuated vaccine within 30 days prior to first dose of belantamab mafodotin.\n31. Participant should not use contact lenses while receiving belantamab mafodotin.\n32. Because of the embryo-fetal risk of lenalidomide, all participants must adhere to the lenalidomide pregnancy prevention program applied in their region.",{"count":129,"type":21},36,[24,70],"This is a phase 1\u002F2, open-label study designed to assess the safety and clinical activity of different belantamab mafodotin doses in combination with lenalidomide, dexamethasone and nirogacestat in patients with transplant ineligible newly diagnosed multiple myeloma.\n\nThis will be a 2-part study. In part 1 participants will be enrolled in one cohort to receive belantamab mafodotin in combination with lenalidomide, dexamethasone and nirogacestat and will determine the recommended phase 2 dose (RP2D) to be further evaluated for safety and clinical activity in the dose expansion cohort. The RP2D dose will be used in future studies in the transplant-ineligible newly diagnosed multiple myeloma (NDMM) setting. In the dose expansion phase (Part 2) an expansion cohort will be treated with the RP2D. The expansion cohort will randomize participants (1:1) in two groups to evaluate two alternate dose modification guidelines for corneal AEs. Part 2 of the study will also evaluate an alternative dose modification guideline for corneal adverse events (AEs).\n\nOverall, approximately 36 participants will be enrolled in the study. Participant follow-up will continue up to 3 years after the last participant is enrolled (follow-up period range: 3-4 years). The estimated accrual period will be 12 months, corresponding to an approximate total study duration of 4 years.",[109,103,133,134,34,35,135,136],"Neoplasm, Plasma Cell","Gammopathy, Monoclonal","Haematologic Disease","Corneal Disease","2023-10-20",{"date":139,"type":50},"2023-10-24",{"date":141,"type":50},"2023-07-14",{"date":143,"type":21},"2026-10-31",{"name":145,"class":87},"Hellenic Society of Hematology",2,{"id":148,"slug":149,"hasResults":11,"nctId":150,"briefTitle":151,"officialTitle":152,"acronym":4,"eligibilityCriteria":153,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":154,"targetDuration":4,"studyType":22,"phases":156,"briefSummary":157,"conditions":158,"keywords":4,"overallStatus":159,"whyStopped":4,"lastUpdateSubmitDate":160,"lastUpdatePostDateStruct":161,"startDateStruct":163,"completionDateStruct":165,"leadSponsor":166,"locationsCount":4},"100483964","phase-1-a-study-to-investigate-the-safety-and-clinical-activity-of-belantamab-mafodotin-in-combination-with-daratumumab-pomalidomide-and-dexamethasone-in-patients-with-relapsed-refractory-multiple-myeloma-previously-treated-with-one-line-therapy-who-are-lenalidomide-refractory-100483964","NCT05581875","A Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin in Combination With Daratumumab, Pomalidomide and Dexamethasone in Patients With Relapsed\u002F Refractory Multiple Myeloma Previously Treated With One Line Therapy Who Are Lenalidomide Refractory","A Phase 1\u002F2, Dose and Schedule Evaluation Study to Investigate the Safety and Clinical Activity of Belantamab Mafodotin Administered in Combination With Daratumumab, Pomalidomide and Dexamethasone in Patients With Relapsed\u002F Refractory Multiple Myeloma Previously Treated With One Line of Therapy Who Are Lenalidomide Refractory.","Inclusion Criteria:\n\n1. Participant must be ≥18 years or older.\n2. Documented diagnosis of Multiple Myeloma (MM) as per International Myeloma Working Group (IMWG) criteria.\n3. Must have at least ONE aspect of measurable disease, defined as one of the following:\n\n   1. Urine M-protein excretion ≥200 mg\u002F24 hrs (≥0.2 g\u002F24 hrs), or\n   2. Serum M-protein concentration ≥0.5 g\u002FdL (≥5.0 g\u002FL), or\n   3. Serum Free Light Chain (FLC) assay: involved FLC level ≥10 mg\u002FdL (≥100 mg\u002FL) and an abnormal serum FLC ratio (\\\u003C0.26 or \\>1.65).\n4. Eastern Cooperative Oncology Group performance status of 0-2.\n5. Adequate organ system function as defined by the below laboratory assessments. Hematologic\n\n   1. Absolute neutrophil count (ANC) ≥1.5 X 109\u002FL; granulocyte colony stimulating factor use within the past 14 days is NOT permitted.\n   2. Hemoglobin ≥8.0 g\u002FdL; transfusions within the past 14 days are NOT permitted. Erythropoietin use is allowed.\n   3. Platelet count ≥50 x 109\u002FL if Bone Marrow (BM) is \\>50% involved in myeloma. Otherwise ≥75 x 109\u002FL; transfusions within the past 14 days are NOT allowed to reach this level.\n\n   Hepatic\n   1. Total bilirubin ≤1.5xULN (isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \\\u003C35%).\n   2. Alanine aminotransferase (ALT) ≤ 2.5xUpper Limit of Normal (ULN). Renal\n\n   \u003C!-- -->\n\n   1. Estimate glomerular filtration rate (eGFR) ≥30 mL\u002Fmin\u002F1.73 m2; calculated using the Modified Diet in Renal Disease (MDRD) formula.\n   2. Spot urine (albumin\u002Fcreatinine ratio) ≤500 mg\u002Fg (56 mg\u002Fmmol) OR\n   3. Urine Dipstick: Negative trace; if ≥1+ only eligible if confirmed ≤500 mg\u002Fg \\[56 mg\u002Fmmol\\] by albumin\u002Fcreatinine ratio (spot urine from first void).\n6. Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:\n\n   A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:\n   * Is not a woman of childbearing potential (WOCBP) defined as follows:\n\n     1. ≥45 years of age and has not had menses for \\> 1 year\n     2. Participants who have been amenorrhoeic for \\\u003C 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation\n     3. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.\n\n        OR\n   * Is a WOCBP and using two methods of reliable birth control (one method that is highly effective and one additional effective \\[barrier\\] method), beginning 4 weeks before initiating treatment with pomalidomide, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of pomalidomide treatment. WOCBP participants must use one method of reliable birth control that is highly effective for 4 months following discontinuation of belantamab mafodotin or 3 months following the discontinuation of daratumumab. WOCBP must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during treatment, during dose interruptions and for 28-days following the last dose of pomalidomide or 3 months following discontinuation of daratumumab treatment or 4 months following discontinuation of belantamab mafodotin treatment whichever is longer.\n\n   A WOCBP must have two negative pregnancy tests before therapy initiation. The first test should be performed within 10-14 days and the second test within 24 hours before the start of pomalidomide therapy.\n\n   The participant should not receive pomalidomide until the Investigator has verified that the results of these pregnancy tests are negative. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. The Investigator is responsible for a review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.\n7. Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:\n\n   Male participants are eligible to participate if they agree to the following during the intervention period and until 28 days after the last dose of pomalidomide or 3 months following the discontinuation of daratumumab or 6 months after the last dose of belantamab mafodotin, whichever is longer, to allow for clearance of any altered sperm.\n\n   • Refrain from donating sperm\n\n   PLUS either:\n   * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR\n   * Must agree to use contraception\u002Fbarrier as detailed below:\n\n   Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \\\u003C1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females).\n8. Participants must be able to understand the study procedures and agree to participate in the study by providing written informed consent.\n9. Participant must have received only 1 prior line of therapy (including lenalidomide) and be lenalidomide refractory at any lenalidomide dose (i.e., nonresponsive while on lenalidomide therapy, or progresses within 60 days of last therapy with lenalidomide).\n\nExclusion Criteria:\n\n1. Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute, Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 5.\n2. Major surgery within 4 weeks before the first dose of study drug\n\n   * NOTE 1: participant must be clinically stable following a major surgery to be entered in the study.\n   * NOTE 2: major surgery shall be defined based on the Investigator's judgment according to the extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes.\n3. Presence of active renal condition (infection, requirement for dialysis, or any other significant condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM are eligible, provided that they fulfil the other inclusion criteria.\n4. Any serious and\u002For unstable pre-existing medical or psychiatric disorder, or other conditions (including laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures.\n5. Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not explained by reversible coagulopathy.\n6. Current active unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis (except for Gilbert's syndrome or asymptomatic gallstones; otherwise, stable non-cirrhotic chronic liver disease; or hepatobiliary involvement of malignancy as per the Investigator's assessment).\n7. Participants with previous or concurrent malignancies other than MM are excluded. Exceptions are surgically treated cervical carcinoma in situ, or any other malignancy that has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease.\n\n   * NOTE: Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction.\n8. Evidence of cardiovascular risk including any of the following:\n\n   * Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities, second degree (Mobitz Type II), or third degree atrioventricular block.\n   * Screening 12-lead ECG showing a baseline QT interval \\>470 msec\n   * History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening.\n   * Class III or IV heart failure as defined by the New York Heart Association functional classification system\n   * Uncontrolled hypertension.\n9. Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second \\[FEV1\\] \\\u003C50% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (controlled intermittent asthma or controlled mild persistent asthma is allowed).\n\n   NOTE: Participants with known or suspected COPD must have a FEV1 test at screening.\n10. Active infection requiring treatment.\n11. Known human immunodeficiency virus infection, unless the participant can meet all of the following criteria:\n\n    * Established anti-retroviral therapy for at least 4 weeks and HIV viral load \\\u003C400 copies\u002FmL.\n    * CD4+ T-cell (CD4+) count ≥350 cells\u002FuL.\n    * No history of AIDS-defining opportunistic infections within the last 12 months.\n\n      * NOTE: consideration must be given to ART and prophylactic antimicrobials that may have a drug:drug interaction and\u002For overlapping toxicities with belantamab mafodotin or other combination products as relevant\n12. To be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \\[HBsAg\\]) at screening or within 3 months prior to first dose of study treatment.\n\n    * NOTE 1: Participants with resolved infection (i.e., participants who are positive for antibodies to hepatitis B core antigen \\[antiHBc\\] or antibodies to hepatitis B surface antigen \\[antiHBs\\]) must be screened using real-time polymerase chain reaction (PCR). Those who are PCR positive will be excluded.\n    * NOTE 2: presence of antiHBs indicating previous vaccination will not constitute an exclusion criterion.\n13. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before the first dose of study treatment unless the participant can meet the following criteria:\n\n    * RNA test negative\n    * Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative hepatitis C virus (HCV) RNA test after a washout period of at least 4 weeks.\n14. Current corneal epithelial disease except for mild punctate keratopathy.\n\n    * NOTE: Participants with mild punctate keratopathy are allowed.\n15. Intolerance or contraindications to anti-viral prophylaxis.\n16. Unable to tolerate antithrombotic prophylaxis.\n17. Active or history of venous thromboembolism within past 3 months.\n18. AL amyloidosis (light chain amyloidosis), active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening.\n19. Exhibiting clinical signs of or with a known history of meningeal or central nervous system involvement by MM.\n20. Known intolerance or immediate or delayed hypersensitivity reaction or idiosyncratic reaction to: drugs chemically related to belantamab mafodotin, or any of the components of the study treatment; daratumumab subcutaneous (SC) or to any of its excipients; or infused protein products, sucrose, histidine, and polysorbate 80.\n21. Use of an investigational drug within 14 days or 5 half-lives (whichever is longer) preceding the first dose of study drug.\n22. Participant who has received prior treatment with daratumumab, pomalidomide or belantamab mafodotin will be excluded.\n\n    * NOTE: Participants who received induction treatment with daratumumab (max 4 cycles) will be allowed as long as 6 months have passed since their treatment with daratumumab and cycle 1 day 1 (C1D1).\n23. Plasmapheresis within 7 days before the first dose of study drug.\n24. Participants with uncontrolled skin disease.\n25. Participant must not have received a live or live-attenuated vaccine within 30 days prior to first dose of belantamab mafodotin.\n26. Participant should not use contact lenses while receiving belantamab mafodotin.",{"count":155,"type":21},48,[24,70],"This is a phase 1\u002F2, open label, single-center study designed to assess the safety and preliminary clinical activity of different belantamab mafodotin doses in combination with daratumumab, pomalidomide, and dexamethasone (DPd) in patients with Relapsed\u002F Refractory Multiple Myeloma (RRMM) previously treated with one line of therapy who are lenalidomide refractory.\n\nThis will be a 2-Part study. Part 1 will evaluate the safety of belantamab mafodotin in combination with DPd in 2 cohorts and determine the Recommended Phase 2 Dose (RP2D). In the dose expansion phase (Part 2) an expansion cohort will be treated with the RP2D. The expansion cohort will randomize participants (1:1) in two groups to evaluate two alternate dose modification guidelines for corneal AEs. Part 2 will further evaluate the safety and assess the preliminary clinical activity of the belantamab mafodotin RP2D in combination with DPd.\n\nOverall, approximately 48 participants will be enrolled in the study. Participant follow-up will continue up to 3 years after the last participant is randomized. The estimated accrual period will be 12 months corresponding to an approximate total study duration of 4 years.",[109,27,103,134,34,35,135,136,102],"NOT_YET_RECRUITING","2022-10-13",{"date":162,"type":50},"2022-10-17",{"date":164,"type":21},"2022-10-20",{"date":143,"type":21},{"name":145,"class":87}]