An Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma (KarMMa-2)
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| ClinicalTrials.gov Identifier: NCT03601078 |
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Recruitment Status :
Recruiting
First Posted : July 26, 2018
Last Update Posted : June 24, 2022
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Sponsor:
Celgene
Information provided by (Responsible Party):
Celgene
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Brief Summary:
This study is a multi-cohort, open-label, multicenter Phase 2 study to evaluate the efficacy and safety of bb2121 in subjects with relapsed and refractory MM (Cohort 1), in subjects with MM having progressed within one 18 months of initial treatment including autologous stem cell transplantation (ASCT) (Cohort 2a), and without ASCT (Cohort 2b) or, in subjects with inadequate response post ASCT during initial treatment (Cohort 2c). Approximately 235 subjects will be enrolled into one of three cohorts. Cohort 1 will enroll approximately 97 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens. Cohort 2a will enroll approximately 39 MM subjects, with 1 prior anti-myeloma therapy including ASCT and with early relapse. Cohort 2b will enroll approximately 39 MM subjects with 1 prior anti-myeloma therapy not including ASCT and with early relapse. Cohort 2c will enroll approximately 30 MM subjects with inadequate response to ASCT during their initial anti-myeloma therapy. The cohorts will start in parallel and independently. Cohort 3 will enroll approximately 30 newly diagnosed multiple myeloma (NDMM) participants with suboptimal response to ASCT.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Biological: bb2121 Drug: Lenalomide | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 235 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2, Multi-cohort, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With Clinical High-Risk Multiple Myeloma (KarMMa-2) |
| Actual Study Start Date : | December 13, 2018 |
| Estimated Primary Completion Date : | December 18, 2023 |
| Estimated Study Completion Date : | December 30, 2030 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
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Experimental: bb2121 in relapsed and refractory multiple myeloma patients
bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 450 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy
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Biological: bb2121
bb2121 consists of autologous T lymphocytes transduced with an anti-BCMA CAR lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR)
Other Name: BMS-986395 |
| Experimental: BB2121 with lenalidomide in newly diagnosed multiple myeloma |
Biological: bb2121
bb2121 consists of autologous T lymphocytes transduced with an anti-BCMA CAR lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR)
Other Name: BMS-986395 Drug: Lenalomide Specified dose on specified days
Other Name: Revlimid® |
Primary Outcome Measures :
- Overall response rate (ORR)- Cohort 1 [ Time Frame: Up to approximately 5 years ]Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator
- Complete response (CR) rate - Cohort 2a , b, c and Cohort 3 [ Time Frame: Up to approximately 5 years ]Percentage of subjects who achieved CR or stringent CR according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator
Secondary Outcome Measures :
- Complete response (CR) rate - Cohort 1 [ Time Frame: Up to approximately 5 years ]Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator
- Overall response rate (ORR) - Cohort 2a, b, c and Cohort 3 [ Time Frame: Up to approximately 5 years ]Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator
- Very good partial response (VGPR) rate - Cohort 2c [ Time Frame: Minimum of 2 years after bb2121 infusion ]Percentage of subjects who achieved VGPR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator
- Time to response (TTR) [ Time Frame: Minimum of 2 years after bb2121 infusion ]Time from first bb2121 infusion to first documentation of response (PR or greater)
- Duration of response (DoR) [ Time Frame: Minimum of 2 years after bb2121 infusion ]Time from first documentation of response (PR or greater) to first documentation of progressive disease (PD) or death from any cause, whichever occurs first
- Progression-free survival (PFS) [ Time Frame: Minimum of 2 years after bb2121 infusion ]Time from first bb2121 infusion to first documentation of PD, or death due to any cause, whichever occurs first
- Time to progression (TTP) [ Time Frame: Minimum of 2 years after bb2121 infusion ]Time from first bb2121 infusion to first documentation of PD
- Overall survival (OS) [ Time Frame: Minimum of 2 years after bb2121 infusion ]Time from first bb2121 infusion to time of death due to any cause
- Adverse Events (AEs) [ Time Frame: Minimum 5 years after bb2121 infusion ]Type, frequency, seriousness and severity of adverse events (AEs), adverse events of special interest (AESIs) (including cytokine release syndrome, neurotoxicity and infection), and relationship of AE to study drug.
- Percentage of participants who received lenalidomide maintenance for the first 3 cycles following bb2121 infusion with at least 75% dose compliance - Cohort 3 [ Time Frame: Up to 3 months ]
- Pharmacokinetics - Cmax [ Time Frame: Minimum 5 years after bb2121 infusion ]Maximum expansion of bb2121 chimeric antigen receptor (CAR) T cells
- Pharmacokinetics - tmax [ Time Frame: Minimum 5 years after bb2121 infusion ]Time to peak of bb2121 CAR T cells
- Pharmacokinetics - AUC [ Time Frame: Minimum 5 years after bb2121 infusion ]Area under the curve of CAR T cells
- Pharmacokinetics - tlast [ Time Frame: Minimum 5 years after bb2121 infusion ]Time to last measurable CAR T cells
- Pharmacokinetics - AUC0-28days [ Time Frame: Minimum 5 years after bb2121 infusion ]Area under the curve of CAR T cells from time zero to Day 28
- Immunogenicity [ Time Frame: Minimum of 2 years after bb2121 infusion ]Development of an anti-CAR antibody response
- Subject-reported outcomes as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30) [ Time Frame: Minimum 5 years after bb2121 infusion ]Questionnaire will be used as a measure of health-related quality of life
- Subject-reported outcomes as measured by EuroQoL Group EQ-5D-5L Health Questionnaire [ Time Frame: Minimum 5 years after bb2121 infusion ]Is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal
- Subject-reported outcomes as measured by EORTC-QLQ-MY20 [ Time Frame: Minimum 5 years after bb2121 infusion ]Is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study:
- Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
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For Cohorts 1 and 2 only, participant has measurable disease, defined as:
- M-protein (serum protein electrophoresis [sPEP] or urine protein electrophoresis [uPEP]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or
- Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
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Subjects with one of the following cohort specific requirements:
Cohort 1 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens:
- Subject must have received at least 3 prior anti-myeloma treatment regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
- Subject must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen
- Subject must have received prior treatment with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody
- Subject has evidence of PD on or within 60 days of the most recent prior treatment regimen
- Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen
Cohort 2 subjects with 1 prior anti-myeloma treatment regimen:
- Subject must have received only 1 prior anti-myeloma treatment regimen. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen
- Subject must have the following HR factors:
- Early relapse defined as:
Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must contain induction, ASCT (single or tandem) and lenalidomide containing maintenance.
Cohort 2b: PD < 18 months since date of start or initial therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone Cohort 2c: Subject must have received minimum 3 cycles of induction therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone. Subjects must have had ASCT (single or tandem AND < VGPR (excluding PD) at first assessment between 70 to 110 days after last ASCT, with initial therapy without consolidation and maintenance. Cohort 3 participants with newly diagnosed MM (NDMM) who received only induction and ASCT, without subsequent consolidation or maintenance Subject with NDMM who have received only induction and ASCT, without subsequent consolidation or maintenance Cohort 3
- With NDMM who have received only induction and ASCT, without subsequent consolidation or maintenance
- Must have received 4 to 6 cycles of induction therapy which must contain at minimum, a proteasome inhibitor and an immunomodulatory agent and must have had single ASCT within 6 months prior to consent
- Must have achieved documented PR or VGPR at first post-ASCT assessment approximately 100 days after ASCT and this response must be maintained at screening
- Per Investigator's assessment, subject must be a candidate for single-agent lenalidomide maintenance
- Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
- Subject used any investigational agents within 14 days prior to leukapheresis or, for Cohort 3, within 14 days prior to consent
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Subject received any of the following within the last 14 days prior to leukapheresis or, for Cohort 3, within 14 days prior to consent:
- Plasmapheresis
- Major surgery (as defined by the investigator)
- Radiation therapy other than local therapy for myeloma associated bone lesions
- Use of any systemic anti-myeloma drug therapy
- Subject with known central nervous system involvement with myeloma
- Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation
- History or presence of clinically relevant central nervous system (CNS) pathology
- Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis
- Inadequate organ function Subject with a history of Class III or IV congestive heart failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months prior to starting study treatment
- Ongoing treatment with chronic immunosuppressants
- Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy
- Subject has received ASCT within 12 weeks prior to leukapheresis
- Subject has history of primary immunodeficiency
- Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C
- Subject has uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment
- Subject with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years
- Pregnant or lactating women
- Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03601078
Contacts
| Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com | 855-907-3286 | Clinical.Trials@bms.com | |
| Contact: First line of the email MUST contain the NCT# and Site #. |
Locations
Show 50 study locations
Sponsors and Collaborators
Celgene
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
| Responsible Party: | Celgene |
| ClinicalTrials.gov Identifier: | NCT03601078 |
| Other Study ID Numbers: |
BB2121-MM-002 U1111-1216-4209 ( Other Identifier: WHO ) 2018-000264-28 ( EudraCT Number ) |
| First Posted: | July 26, 2018 Key Record Dates |
| Last Update Posted: | June 24, 2022 |
| Last Verified: | June 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Celgene:
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Multiple Myeloma bb2121 Relapsed and Refractory Multiple Myeloma High Risk Multiple Myeloma |
Phase 2 Multi-cohort Open-label |
Additional relevant MeSH terms:
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders |
Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Lenalidomide Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Antineoplastic Agents |