[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"high-risk-smoldering-multiple-myeloma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:high-risk-smoldering-multiple-myeloma":26},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,3,0,[8,43,74],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":29,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":32,"lastUpdatePostDateStruct":33,"startDateStruct":36,"completionDateStruct":38,"leadSponsor":40,"locationsCount":5},"100475358","phase-2-immuno-prism-precision-intervention-smoldering-myeloma-100475358",false,"NCT05469893","Immuno-PRISM (PRecision Intervention Smoldering Myeloma)","Immuno-PRISM (PRecision Intervention Smoldering Myeloma): A Randomized Phase II Platform Study of Select Immunotherapies for High-Risk Smoldering Myeloma","Inclusion Criteria:\n\n* Age ≥18 years.\n* 1\\) High risk SMM defined as having 1 of the following 2 criteria: High risk per \"20-2-20\" Criteria defined as presence of any two of the following:\n\n  \\-- Serum M spike ≥ 2 gm\u002FdL, Involved to uninvolved free light chain (FLC) ratio≥ 20, Bone marrow Plasma Cell (BMPC) % ≥ 20%\n* OR total score of 9 using the following scoring system:\n\n  * FLC Ratio \\>10-25 = 2, \\>25-40 = 3, \\> 40 = 5\n  * Serum M-Protein (g\u002FdL) \\>1.5-3 = 3, \\>3 = 4\n  * BMPC% \\>15-20 = 2, \\>20-30 = 3, \\>30-40 = 5, \\>40 = 6\n* Fluorescence In Situ Hybridization (FISH) abnormality (t(4,14), t(14,16), 1q gain, or del13q = 2\n* 2\\) Presence of ≥10% BMPC and at least one of the following:\n\n  \\-- Evolving pattern:\n  * evolving Monoclonal Protein (eMP) (≥10% increase in Monoclonal Protein\u002FImmunoglobulin (Ig)) within the first 6 months (only if M-protein ≥3 g\u002Fdl) and\u002For ≥25% increase in M\u002FIg within the first 12 months, with a minimum required increase of 0.5 g\u002Fdl in M-protein and\u002For 500 mg\u002Fdl in Ig.\n  * Evolving change in hemoglobin (eHb) ≥0.5 g\u002Fdl decrease within 12 months of diagnosis;\n  * Progressive involved light chain increase on two successive evaluation\n  * Abnormal Plasma Cell immunophenotype (≥ 95% of BMPCs are clonal) and reduction of ≥1 uninvolved immunoglobulin isotype. (Only IgG; IgA and IgM will be considered)\n  * High risk cytogenetics defined as presence of t(4;14), t(14;16), t(14;20), 17p deletion, TP53 mutation, 1q21 gain\n  * Monoclonal light chain excretion of \\> 200mg\u002F24 hours for those with monoclonal light chain SMM\n* No evidence of CRAB criteria\\* or new criteria of active MM (SLIM-CRAB) which include the following:\n\n  * Increased calcium levels: Corrected serum calcium \\>0.25 mmol\u002FL (\\>1mg\u002FdL) above the upper limit of normal or \\>2.75 mmol\u002FL (\\>11mg\u002FdL);\n  * Renal insufficiency (attributable to myeloma);\n  * Anemia (Hgb 2g\u002FdL below the lower limit of normal or \\\u003C10g\u002FdL);\n  * Bone lesions (lytic lesions or generalized osteoporosis with compression fractures)\n  * No evidence of the following new criteria for active MM including the following:\n\n    * Bone marrow plasma cells \\>60%\n    * Serum involved\u002Funinvolved FLC ratio ≥100\n    * MRI with more than one focal lesion\n* Participants with CRAB criteria that are attributable to conditions other than the disease under study may be eligible after discussion with the Sponsor Investigator.\n* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1, or 2\n* The following laboratory values obtained \\\u003C28 days prior to registration:\n\n  * Absolute Neutrophil Count (ANC) \\>1000\u002FmL\n  * Platelets Count (PLT) \\>75,000\u002FmL\n  * Total bilirubin ≤ 2.0 mg\u002FdL (If total is elevated check direct and if normal patient is eligible.)\n  * Aspartates Aminotransferase (AST) \\\u003C2.5 x institutional upper limit of normal (ULN)\n  * Alanine Transaminase (ALT) \\\u003C2.5 x institutional upper limit of normal (ULN)\n  * Estimated creatinine clearance (CLcr) ≥60 mL\u002Fmin\n* Voluntary written informed consent will be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.\n* Females of child-bearing potential\\* randomized to Lenalidomide must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU\u002FmL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by Revlimid Risk Evaluation and Mitigation Strategies (REMS®) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide.\n\n  * A female of child-bearing potential is a sexually mature female who: has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries), or 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 during the preceding 24 consecutive months)\n  * A woman must be . A Not of childbearing potential, or b. Of childbearing potential and Practicing true abstinence; or Have a sole partner who is vasectomized; or Practicing ≥1 highly-effective, user-independent method of contraception NOTE: Participant must agree to continue the above throughout the study and for 90 days after the last dose of study treatment.\n\nNOTE: If a woman becomes of childbearing potential after start of the study the woman must comply with point (b) as described above.\n\nNOTE: An interaction between hormonal contraception and teclistamab has not been formally studied. Therefore, it is unknown whether teclistamab may reduce the efficacy of the contraception method.\n\n* A woman must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for 90 days after receiving the last dose of study treatment\n* A man must wear a condom (with or without spermicidal foam\u002Fgel\u002Ffilm\u002Fcream\u002Fsuppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 90 days after receiving the last dose of study treatment. If a female partner is of childbearing potential, she must also be practicing a highly effective method of contraception\n* If the male participant is vasectomized, he still must wear a condom (with spermicidal foam\u002Fgel\u002Ffilm\u002Fcream\u002Fsuppository), but his female partner is not required to use contraception.\n* A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study treatment.\n* Must be willing and able to adhere to the lifestyle restrictions specified in this protocol\n* All study participants randomized to lenalidomide must be registered into the mandatory Revlimid REMS® program and be willing and able to comply with the requirements of the REMS® program.\n* Females of child-bearing potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program if randomized to lenalidomide\n* Men must agree to use a latex condom during sexual contact with a female of childbearing potential even if they have had a successful vasectomy\n* Ability to understand and the willingness to sign a written informed consent.\n\nExclusion Criteria:\n\n* Prior SMM directed therapy administered within 6 months of beginning treatment on study. To avoid including primary refractory cases to the lenalidomide arm, participants who received a prior lenalidomide-based therapy should have had at least an Minimal Response (MR) to be considered on this trial.\n* Symptomatic Multiple Myeloma or any evidence of CRAB criteria, including presence of myeloma defining events (MDE). Any prior therapy for active Myeloma should also be excluded. Prior therapy for smoldering myeloma is not an exclusion criterion. Bisphosphonates are not excluded\n* Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational. Prior therapy with bisphosphonate is allowed. Prior radiation therapy to a solitary plasmacytoma is allowed but had to be at least 6 months prior to enrollment on the trial. Prior clinical trials or therapy for smoldering MM or Monoclonal Gammopathy of Unknown Significance (MGUS) are allowed per exclusion criteria described above.\n* Serious medical or psychiatric illness likely to interfere with participation in this clinical study.\n* Diagnosed or treated for another malignancy within 2 years of enrollment\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Plans to father a child while enrolled in this study or within 90 days after receiving the last dose of study drug.\n* Pregnant or breast-feeding or planning to become pregnant while enrolled in this study or within 90 days after receiving the last dose of study drug.\n* Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) or SARS-CoV-2 (COVID- 19).\n* Participants who are seropositive because of hepatitis B virus vaccine are eligible.\n* Participants who are positive for SARS-COV-2 antibody, HIV1 and 2 antibody, hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.\n* Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the teclistamab Investigator's Brochure and appropriate package inserts).\n* Prior or concurrent exposure to any of the following:\n* Investigational vaccine within 4 weeks\n* Live, attenuated vaccine within 4 weeks before randomization.\n* Monoclonal antibody therapy within 21 days\n* Cytotoxic therapy within 14 days\n* PI therapy within 14 days\n* IMiD agent therapy within 14 days\n* Radiotherapy within 14 days or focal radiation within 7 days\n* A maximum cumulative dose of corticosteroids of ≥140 mg of prednisone or equivalent within 14-day period before the first dose of study drug (does not include pretreatment medications)\n* Known active Central Nervous System (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required.\n* Myelodysplastic syndrome or active malignancies (i.e., progressing or requiring treatment change in the last 24 months). The only allowed exceptions are: a. Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured. c. Noninvasive cervical cancer treated within the last 24 months that is considered completely cured d. Localized prostate cancer (N0M0): With a Gleason score of ≤6, treated within the last 24 months, or untreated and under surveillance With a Gleason score of 3+4 that has been treated \\>6 months prior to full study screening and considered to have a very low risk of recurrence, or e. History of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence. f. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence. g. Other malignancy that is considered cured with minimal risk of recurrence\n* Stroke or seizure within 6 months prior to signing informed consent form\n* Presence of the following cardiac conditions:\n\n  \\-- New York Heart Association stage III or IV congestive heart failure, 2) Myocardial infarction or coronary artery bypass graft ≤6 months prior to randomization,3) History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration,4) History of severe non-ischemic cardiomyopathy\n* Major surgery within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment. NOTE: Participants with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery. If there is a question whether a procedure is considered a major surgery, the investigator must consult with the appropriate sponsor representative and resolve any issues before enrolling a participant in the study.\n* Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study, such as:\n* Uncontrolled diabetes defined by Hemoglobin A1C \\> 8.5, Acute diffuse infiltrative pulmonary disease, Evidence of active systemic viral, fungal, or bacterial infection, requiring systemic, antimicrobial therapy, History of autoimmune disease with the exception of vitiligo, type I diabetes, and, prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing, . Disabling psychiatric conditions (e.g., alcohol or drug abuse), severe dementia, or altered mental status, Any other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the wellbeing) or that could prevent, limit, or confound the protocol-specified assessments, History of non-compliance with recommended medical treatments","ALL","18 Years",{"count":19,"type":20},52,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","The purpose of this study is to test the anti-cancer activity of Teclistamab and to compare it with Lenalidomide + Dexamethasone combination in people with high risk smoldering multiple myeloma.\n\nPeople with smoldering multiple myeloma (SMM) usually do not have symptoms but are at risk for progressing to active multiple myeloma (MM). Multiple Myeloma is a cancer of the plasma cells, which are an important part of the immune system. Patients with active multiple myeloma generally require treatment but there are currently no approved therapies for smoldering multiple myeloma.\n\nThe names of the study drugs involved in this study are:\n\n* Teclistamab\n* Lenalidomide (also called Revlimid)\n* Dexamethasone (also called Decadron)",[26,27,28],"High-risk Smoldering Multiple Myeloma","Smoldering Multiple Myeloma","Multiple Myeloma",[30,27,28],"High-risk smoldering Multiple Myeloma","RECRUITING","2025-04-22",{"date":34,"type":35},"2025-04-24","ACTUAL",{"date":37,"type":35},"2022-08-10",{"date":39,"type":20},"2030-07-31",{"name":41,"class":42},"Irene Ghobrial, MD","OTHER",{"id":44,"slug":45,"hasResults":11,"nctId":46,"briefTitle":47,"officialTitle":48,"acronym":4,"eligibilityCriteria":49,"healthyVolunteers":50,"sex":16,"minAge":17,"maxAge":51,"enrollmentInfo":52,"targetDuration":4,"studyType":21,"phases":54,"briefSummary":56,"conditions":57,"keywords":59,"overallStatus":63,"whyStopped":4,"lastUpdateSubmitDate":64,"lastUpdatePostDateStruct":65,"startDateStruct":67,"completionDateStruct":69,"leadSponsor":71,"locationsCount":73},"100573392","bcmacd3-bsab-in-the-treatment-of-high-risk-smoldering-multiple-myeloma-100573392","NCT06745687","BCMA\u002FCD3 BsAb in the Treatment of High-risk Smoldering Multiple Myeloma","A Prospective, Multi-center, Single-arm Clinical Trial of BCMA\u002FCD3 BsAb in the Treatment of High-risk Smoldering Multiple Myeloma","Inclusion Criteria:\n\n1. Know and voluntarily sign an informed consent form (ICF).\n2. Age ≥18 years.\n3. Definite diagnosis of SMM: According to IMWG Criteria 10, the patient must have histologically or cytologically confirmed smoldering multiple myeloma (SMM), including:\n\n   1. Serum M protein ≥3 g \u002FdL and\u002For BMPCs≥10%(but not more than 60%)\n   2. No anemia: hemoglobin ≥10 g \u002FdL\n   3. No renal failure: serum creatinine ≥2.0 mg\u002FdL\n   4. No hypercalcemia: calcium ≥10.5 mg\u002FdL\n   5. dissolving bone lesions without radiographic indications: X-ray, CT, or positron emission tomography (PET)\u002FCT without dissolving bone lesions, with no more than 1 lesion on whole-body MRI (Note: In the investigator's judgment, whole-body CT or PET\u002FCT may replace MRI for patients with contraindications or for whom MRI is not available).\n   6. FLC ratio \\\u003C100 (unless light chain ≤10 mg \u002FdL is involved) Note: Anemia, renal failure and hypercalcemia are allowed if there is evidence that anemia, renal failure, hypercalcemia or bone lesions are not associated with multiple myeloma (MM).\n4. High-risk SMM are defined as meeting one or more of the three criteria in the following part: (i) Mayo 2018, (ii) IMWG 2020 and (iii) evolving pattern.\n\n   (i)Mayo 2018\n   * M protein \\> 2 g\u002FdL ② The ratio of affected to unaffected FLC was \\> 20 ③BMPC \\> 20% of the 3 items meet any 2 or more\n\n   (ii) IMWG 2020\n   * FLC ratio 0-10: 0 points 10-25: 2 points 25-40: 3 points \\>40: 5 points\n\n     ②M protein (g\u002FdL) 0-1.5: indicates 0 points 1.5-3: 3 points \\>3: 4 points\n\n     ③BMPC (%) 0-15: 0 points 15-20: 2 points 20-30: 3 points 30-40: 5 points \\>40: 6 points\n\n     ④FISH \\* : Yes: 2 points None: 0 points The sum of the four points is greater than or equal to 9 （iii）Progression model\n   * Necessary condition: BMPC\\>10% ② Sufficient conditions: a. Serum M protein \\>3 g\u002FdL b. IgA type SMM c. Immune paralysis (reduction of two uninvolved homologous immunoglobulins) d. The proportion of free light chain (FLC) in serum that is affected\u002Fnot affected \\> 8 (but \\\u003C100) e.M protein level increased (SMM type increased; Serum M protein level was increased by ≥25% twice in 6 months.\n\n   F.BMPC: 50%-59% g. Abnormal plasma cell immunophenotype (95% + of cloned BMPC) and reduction of one or more uninvolved immunoglobulin types.\n\n   h.≥5% of cells had chromosomal abnormalities (t (4,14) or del 17 p or 1 q acquisition i. Increased circulating plasma cells (PCs\\>5×106\u002FL or 5%) j. Merri indicates diffuse abnormalities or 1 focal lesion, and\u002For increased uptake of focal lesion in PET-CT class without underlying osteolytic osteopathy. Meet the necessary conditions, 1 or more sufficient conditions.\n\n   \\*FISH exceptions are defined as the presence of any of the following: t (4,14), t (14,16), 1 q amplification, del 13 qt, t (4,20)\n5. ECOG physical status score ≤2 points.\n6. Meeting the following laboratory indicators within 28 days prior to study participation:\n\n   a. neutrophils absolute value (ANC) \\>1000\u002Fml b. Platelet count (PLC)\\> 75,000 \u002Fml c. Total bilirubin ≤2 mg\u002FdL d. Glutamic oxalic aminotransferase (AST) \\\u003C2.5 times the conventional upper limit (ULN) e. Alanine aminotransferase (ALT) \\\u003C2.5 times the upper limit of normal (ULN) f. Estimated creatinine clearance (CLcr)≥60 mL\u002Fmin.\n7. Non-childbearing women meet the entry requirements; Female patients of childbearing age must have a negative serum (beta-human chorionic gonadotropin) or urine pregnancy test at the time of screening.\n8. Men, women of childbearing age, and their partners voluntarily use contraception deemed effective by investigators during treatment and for at least three months after CAR T cell transfusion.\n9. Male patients must agree not to donate sperm from the initial screening period until 90 days after the last medication.\n10. Patients must be willing and able to complete study procedures and follow-up examinations.\n\nNote: Fertile women are all women who have begun menstruating and are not in late menopause and who have not undergone surgical sterilization (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy). Postmenopause is defined as more than 12 consecutive months of amenorrhea for an unspecified reason. Women who are using mechanical birth control methods such as oral contraceptives or intrauterine devices should be considered fertile. Male subjects (including those who have undergone vasectomy) must consent to the use of condoms during sex with women of childbearing age and must not plan to impregnate the woman during the study drug use period from the date of signing the informed consent form and within 3 months after the last study drug receipt.\n\nExclusion Criteria:\n\n1. Diagnosis of symptomatic multiple myeloma: refer to the Chinese Guidelines for Diagnosis and Treatment of multiple myeloma (revised in 2022);\n2. Along with other tumors that must be treated.\n3. Previously received immunotherapy against BCMA targets.\n4. The researchers judged that BCMA\u002FCD 3 dual antibody therapy is not suitable, such as severe cardiopulmonary disease and other conditions that are not suitable for BCMA\u002FCD 3 dual antibody therapy.\n5. Received SMM treatment within six months.\n6. Known intolerance, allergy or contraindications to BCMA\u002FCD 3 dual anti-active ingredients.\n7. Patients with unstable or active cardiovascular and cerebrovascular diseases meet any of the following criteria:\n\n   1. Unstable angina pectoris, symptomatic myocardial ischemia, myocardial infarction, or coronary artery reconstruction had occurred within 180 days prior to initial administration.\n   2. Uncontrolled hypertension (\\>140\u002F90 MMHG, with a blood pressure fluctuation of more than 180\u002F100 MMHG over 6 months);\n   3. Uncontrolled and clinically significant conduction abnormalities (e.g., patients with ventricular arrhythmias controlled by antiarrhythmic drug therapy), not excluding patients with first-degree AV block or asymptomatic left anterior bundle branch block\u002Fright bundle branch block (LAFB\u002FRBBB);\n   4. Echocardiographic left ventricular ejection fraction (LVEF) \\\u003C 40%;\n   5. History of stroke or intracranial hemorrhage within 12 months prior to screening;\n   6. Severe thrombotic events before treatment.\n\n9\\) Known active human immunodeficiency virus (HIV) infection or HIV seropositivity.\n\n10\\) Active hepatitis B or C infection. Screening requires hepatitis serological testing. If hepatitis B surface antigen is positive, a negative DNA polymerase chain reaction (PCR) result is required to be confirmed before enrollment (after anti-HBV treatment, a negative DNA polymerase PCR result is required before enrollment). If the hepatitis C antibody is positive, an RNA PCR test is performed and the result before enrollment is confirmed to be negative.\n\n11\\) Pregnant or lactating women. 12) Any active gastrointestinal dysfunction that affects the patient's ability to swallow pills, or any active gastrointestinal dysfunction that may affect the absorption of investigational therapeutic drugs.\n\n13\\) Patients had major surgery (for example, requiring general anesthesia) within 2 weeks before enrollment began, or will not fully recover from surgery, or have surgery scheduled during the time they plan to participate in the study. Kyphoplasty or spondyloplasty is not considered major surgery. Note: Patients who plan to perform surgery under local anesthesia may participate in the study.\n\n14\\) Received live attenuated vaccine within 4 weeks prior to administration of the first investigational drug.",true,"78 Years",{"count":53,"type":20},20,[55],"NA","The purpose of this study is to evaluate the safety and efficacy of CM-336, which is a BCMA\u002FCD3 BiTE, in the treatment of high risk smoldering multiple myeloma.",[58],"High Risk Smoldering Multiple Myeloma",[60,61,62],"high risk smoldering multiple myeloma","BCMA\u002FCD3 BiTE","CM-336","NOT_YET_RECRUITING","2024-12-17",{"date":66,"type":35},"2024-12-20",{"date":68,"type":20},"2024-12-30",{"date":70,"type":20},"2028-08-01",{"name":72,"class":42},"Institute of Hematology & Blood Diseases Hospital, China",1,{"id":75,"slug":76,"hasResults":11,"nctId":77,"briefTitle":78,"officialTitle":79,"acronym":80,"eligibilityCriteria":81,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":82,"targetDuration":4,"studyType":21,"phases":83,"briefSummary":84,"conditions":85,"keywords":86,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":89,"lastUpdatePostDateStruct":90,"startDateStruct":92,"completionDateStruct":94,"leadSponsor":96,"locationsCount":73},"100560206","phase-2-ciltacabtagene-autoleucel-in-high-risk-smoldering-multiple-myeloma-100560206","NCT06574126","Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma","Phase II Open-Label, Single Arm, Multicenter Study of Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma (GEM-CAR-HiRiSMM)","CAR-HiRiSMM","Inclusion Criteria:\n\n\\- Be ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.\n\n\\- High-risk SMM defined as having 1 of the following 2 criteria: i) High-risk per \"Mayo 20-2-20\" criteria defined as presence of any ≥2 of the following:\n\n1. Serum M-protein ≥2 gm\u002FdL\n2. Involved to uninvolved FLC ratio ≥20\n3. BMPC % ≥20% to \\\u003C40% OR ii) Presence of ≥95% of BMPC with an aberrant phenotype within the BMPC compartment and immunoparesis present defined as a reduction of at least 25% below the lower normal limit for ≥1 uninvolved immunoglobulin isotype (only IgG, IgA and IgM will be considered).\n\n   \\- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1.\n\n   \\- Have an estimated glomerular filtration rate (eGFR), based on the Modified Diet in Renal Disease (MDRD) 4-variable formula or 24-hour urine collection of ≥40 mL\u002Fmin during the screening period.\n\n   \\- Laboratory values obtained \\\u003C21 days prior to Screening: i) Total bilirubin ≤2.0 mg\u002FdL ii) Aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) iii) Alanine transaminase (ALT) ≤3 x ULN\n\n   \\- Hemoglobin ≥8.0 g\u002FdL (≥5 mmol\u002FL) (without prior red blood cell \\[RBC\\] transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted). For subjects who meet the inclusion criteria at screening, transfusion of RBCs is permitted after screening as needed to maintain a hemoglobin level ≥8.0 g\u002FdL.\n\n   \\- Neutrophils ≥1.0 × 109\u002FL (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test)\n\n   \\- Platelets ≥75 × 109\u002FL (must be without transfusion support in the 7 days prior to the laboratory test)\n\n   \\- Lymphocyte count ≥0.3\\*109\u002FL\n\n   \\- Participants should be seronegative for human immunodeficiency virus (HIV) or have controlled disease if seropositive.\n\n   \\- A female participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study.\n\n   \\- A female participant must be either of the following: i) Not of childbearing potential ii) Of childbearing potential and practicing at least 1 highly effective method of contraception throughout the study and through 6 months after the last dose of study treatment. If a female participant becomes of childbearing potential after the start of the study, the female participant must comply with ii).\n\n   \\- A female participant using oral contraceptives should use an additional barrier contraceptive method.\n\n   \\- A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the cilta-cel infusion. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility.\n   * A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 1 year after receiving the cilta-cel infusion. If the male participant's partner is a female of childbearing potential, the male participant must use condoms (with or without spermicide) and the female partner of the male participant must also be practicing a highly effective method of contraception. A male participant who is vasectomized must still use a condom (with or without spermicide), but the partner is not required to use contraception.\n   * A male participant must agree not to donate sperm for the purposes of reproduction during the study and for 1 year after receiving the last dose of study treatment. Male participants should consider preservation of sperm prior to study treatment as anti-cancer treatments may impair fertility.\n   * A male participant must agree not to plan to father a child while enrolled in this study or within 1 year after the last dose of study treatment.\n   * Must sign an informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study\n   * An additional ICF will be collected to get participants authorization to collect the necessary samples for performing the Biological studies indicated in this protocol.\n   * Be willing and able to adhere to the lifestyle restrictions specified in this protocol.\n\n   Exclusion Criteria:\n\n   \\- History of uncontrolled illness, including but not limited to MGUS, standard risk smoldering myeloma, active myeloma by current IMWG definition, light chain amyloidosis with organ involvement or patients with extramedullary disease.\n\n   \\- Non-muscle-invasive bladder cancer treated within the last 24 months that is considered completely cured.\n\n   \\- Skin cancer (nonmelanoma or melanoma) treated within the last 24 months that is considered completely cured.\n   * Noninvasive cervical cancer treated within the last 24 months that is considered completely cured.\n   * Localized prostate cancer (N0M0):\n\n     i) with a Gleason score ≤6, treated within the last 24 months or untreated and under surveillance.\n\n   ii) with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence.\n\n   iii) history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence).\n\n   \\- Adequately treated lobular carcinoma in situ or ductal carcinoma in situ.\n\n   \\- History of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence.\n\n   \\- Known allergies, hypersensitivity, or intolerance to cilta-cel or its excipients.\n\n   \\- Participant had major surgery or had significant traumatic injury ≤14 days prior to Cycle1Day1.\n   * If any of the following exist at screening, participant will be excluded because this trial involves an investigational agent whose genotoxic, mutagenic, and teratogenic effect on the developing fetus and newborn are unknown:\n\n     i) Pregnant women ii) Nursing women iii) Men or women of childbearing potential who are unwilling to employ adequate contraception\n   * Other comorbidity which would interfere with subject's ability to participate in trial, eg, uncontrolled infection, uncompensated heart, or lung disease.\n   * Any medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.\n   * History of neurodegenerative disease (eg, Parkinson or stroke within 6 months).\n   * Medical history of treatment for another malignancy \\\u003C2 years before trial enrollment, other concurrent chemotherapy, or any ancillary therapy considered investigational. Note: Bisphosphonates are considered supportive care rather than therapy and are thus allowed while on protocol treatment.\n   * Known seropositive for or active viral infection with HIV, HBV, hepatitis C virus (HCV), or SARS-CoV-2 (Coronavirus Disease 2019 \\[COVID-19\\]).\n\n     i) Participants who are positive for SARS-COV-2 antibody, HIV1 and 2 antibody, hepatitis B core antibody (HBc), or hepatitis B surface antigen (HBsAg) must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.\n\n   ii) Participants who are positive for HIV1 or 2 infections, with undetectable viral load and on stable antiretrovirals, will not be excluded.\n\n   iii) Participants with past HCV infection need at least 12 months of sustained virologic response and be negative for RNA to enter.\n\n   iv) Patients with a high-risk of HBV reactivation (eg, negative for HBV antigen but positive for chronic HBV, with or without anti-serum HBV) must be monitored with DNA and ALT\u002FAST).\n\n   \\- Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.\n\n   NOTE: Investigators must ensure that all study enrollment criteria have been met at screening. If a participant's clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study intervention is given such that the participant no longer meets all eligibility criteria, then the participant must be excluded from participation in the study.",{"count":53,"type":20},[23],"This is an open-label, single arm, multicenter, interventional study with Dara-VRD followed by cilta-cel in high-risk smoldering multiple myeloma (SMM) patients.\n\nThe primary objectives of this trial, related with efficafy and safety of the treatment, are i) to evaluate the proportion of high-risk SMM patients with undetectable minimal residual disease (MRD) at 6 months, 12 months, and thereafter every 12 months up to 5 years after cilta-cel administration as well as the sustained undetectable MRD rate in the intent-to-treat (ITT) population; ii) to annotate frequency and severity of adverse events (AE) and serious adverse events (SAE), as well as data from laboratory tests aslo related with safety such as Immunoglobulin (Ig) G levels, complete blood count (CBC) cytopenia adn T-cell populations. Secondary objectives are related with response to therapy and will measure different categories of response and survival.",[58],[87,88],"Smoldering Multiple Myoloma","CAR T-cells","2024-10-23",{"date":91,"type":35},"2024-10-26",{"date":93,"type":35},"2024-09-30",{"date":95,"type":20},"2032-09-30",{"name":97,"class":42},"PETHEMA Foundation"]