Multiple MyelomaPhase 2NCT05032820
Upfront Chimeric Antigen Receptor T-Cell to Upgrade Response in Multiple Myeloma
A Phase 2 study testing Lenalidomide, bb2121 and Cyclophosphamide in people with Multiple Myeloma, run by Medical College of Wisconsin at 15 sites in United States.
Trial summary
This study is designed as a Phase II, multicenter, single arm trial to assess anti-B Cell Maturation Antigen (BCMA) chimeric antigen receptor (CAR) T-cells (bb2121) to improve post autologous hematopoietic cell transplant (HCT) responses among patients with multiple myeloma (MM). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Lenalidomide, bb2121 and Cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 15 sitesUnited States
- Study dates
- 5 Jan 2022to 20 Feb 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age greater than or equal to 18.00 years
- Patients must meet the criteria for symptomatic MM requiring therapy (Appendix A) prior to initiating initial systemic anti-myeloma treatment.
- Patients must have received initial systemic anti- myeloma therapy consisting of induction therapy and consolidation with high-dose melphalan (>140 mg/m^2 ) followed by an auto HCT (minimum cell dose of 2x10^6 CD34+ cells/kg (actual body weight) within 12 months from initiation of systemic anti-myeloma therapy.
- Patient must have additional stored stem cells greater than or equal to 2x10^6 CD34+ cells per kg actual body weight.
- Patients must be less than or equal to 12 months after autologous HCT at the time of enrollment.
- Patients must have initiated maintenance therapy with lenalidomide-based regimen within 6 months after the auto HCT and have received at least 3 months of maintenance prior to enrollment.
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- Patients must have tolerated a minimum dose of lenalidomide 5 mg/day for 21 days of a 28-day cycle for greater than 2 cycles without having to stop due to toxicities.
- Patients must have a VGPR or less (Section 3.1) in reference to time time of initiation of initial systemic anti-myeloma therapy at study enrollment.
- Patients must have Karnofsky performance greater than or equal to 70.
- Patients must have recovered to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding Grade 2 neuropathy.
- Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 without filgrastim use in the prior 14 days.
- Platelet count greater than 100,000/mm^3 (without platelet transfusion in the previous 7 days or thrombopoietin mimetics in the previous 28 days).
- Hemoglobin greater than 9 g/dL (without red blood cell transfusion in the previous 7 days).
- Creatinine Clearance (CrCl) greater than or equal to 60 mL/min, measured or estimated by Cockcroft-Gault equation.
- Corrected serum calcium less than or equal to 13.5 mg/dL.
- Oxygen saturation greater than 92% on room air.
- Hepatic Function: a. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal (ULN) b. Serum total bilirubin less than or equal to 2 x ULN. Patients who have been diagnosed with Gilbert's disease are permitted to exceed the defined bilirubin value of 2 x ULN
- International ratio (INR) or partial thromboplastin time (PTT) less than 1.5 x ULN
- Cardiac Function: left ventricular ejection fraction greater than 45% by echocardiogram or MUGA.
- Patients must be willing and able to adhere to the study visit schedule and other protocol requirements including regulatory requirement of a 15 year follow up using the CIBMTR long term follow up mechanism.
- Female patients of childbearing potential (FCBP1 ) must: a. Have a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL prior to enrollment b. Agree to use, and be able to comply with, TWO acceptable methods of birth control (Appendix C), one highly effective method and one additional effective (barrier) method AT THE SAME TIME, from screening through at least 1 year following bb2121 infusion or 4 weeks following discontinuation of lenalidomide, whichever is later. c. Agree to abstain from breastfeeding from screening through at least 1 year following bb2121 infusion or 4 weeks following discontinuation of lenalidomide, whichever is later.
- Male patients must: a. Agree to use a condom during sexual contact with a pregnant female or a FCBP, even if he has undergone a successful vasectomy, from screening through at least 1 year following bb2121 infusion or 4 weeks following discontinuation of lenalidomide whichever is later b. Must not donate sperm from screening through at least 1 year following bb2121 infusion or 4 weeks following discontinuation of lenalidomide whichever is later.
Who cannot join
- Patients with a prior allogeneic hematopoietic cell.
- Female of childbearing potential (FCBP) is a female who:
- has achieved menarche at some point,
- has not undergone a hysterectomy or bilateral oophorectomy 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 in the preceding 24 consecutive months).
- Patients with disease progression (see Section 3.1.2 for disease progression definition) at any time prior to enrollment.
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- Patients receiving any of the following less than 14 days prior to enrollment:
- Plasmapheresis
- Major surgery (as defined by the investigator)
- Radiation therapy other than local therapy for MM-associated bone lesions
- Use of any systemic anti-myeloma drug therapy (with the exception of lenalidomide maintenance)
- Any investigational agents
- Corticosteroids (Physiologic replacement, topical, intranasal and inhaled steroids are permitted)
- Patients with known Central Nervous System (CNS) involvement with MM.
- Patients with a prior organ transplant requiring systemic immunosuppressive therapy.
- Patients who previously experienced toxicities related to lenalidomide resulting in permanent treatment discontinuation.
- Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with an immunomodulatory agent (IMiD).
- Patients unwilling to take DVT prophylaxis while on lenalidomide maintenance.
- Patients with history of greater than or equal to Grade 2 hemorrhage within 30 days of enrollment.
- Patient requiring ongoing treatment with chronic, therapeutic dosing of anticoagulants (e.g. Warfarin, low molecular weight heparin, Factor Xa inhibitors).
- Patients with history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or other CNS bleed, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
- Patients with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically significant amyloidosis.
- Patients with purely non-secretory MM [prior to starting systemic therapy, absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques and the absence of involved serum free light chain greater than 100mg/L]. Patients with light chain MM detected in the serum by free light chain assay are eligible.
- Patients with a history of Class III or IV congestive heart failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or hemodynamically significant ventricular arrhythmia within the previous 6 months prior to starting study treatment.
- Patients with ongoing treatment with chronic immunosuppressants (e.g. cyclosporine or systemic steroids at any dose). Physiologic replacement, intermittent topical, inhaled or intranasal corticosteroids are allowed.
- Patients with active clinically significant autoimmune disease, defined as a history of requiring systemic immunosuppressive therapy and at ongoing risk for potential disease exacerbation. Patients with a history of autoimmune thyroid disease, asthma, or limited skin manifestations are potentially eligible.
- Patients seropositive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or C, or acute hepatitis A. If any history of exposure to hepatitis B or C then DNA PCR should be negative.
- Patients with previous history of treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy.
- Patients with prior malignancies except resected basal cell carcinoma or treated carcinoma in situ. Cancer treated with curative intent less than 5 years prior to enrollment will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs. Cancer treated with curative intent greater than 5 years prior to enrollment is allowed.
- Female patients who are pregnant (positive beta-HCG), or breastfeeding, or who intend to become pregnant during participation in the study.
- Patient with known allergy or hypersensitivity to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- Patient with serious medical of psychiatric illness likely to interfere with participation on this clinical study.
- Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
- Patients unwilling or unable to provide informed consent 25. Patients unable or unwilling to return to the transplant center for treatment and follow up.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Roswell Park Cancer Center
Buffalo, New York, 14203
University of Virginia
Charlottesville, Virginia, 22908
City of Hope National Medical Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27705
Baylor College and Medicine
Houston, Texas, 77030
University of Wisconsin Hospitals and Clinics
Madison, Wisconsin, 53792
Loyola University Medical Center
Maywood, Illinois, 60153
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Mount Sinai Medical Center
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Stanford Hospital and Clinics
Palo Alto, California, 94305
University of Pennsylvania Hospital Center
Philadelphia, Pennsylvania, 19104
University of California, San Francisco
San Francisco, California, 94143
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: Phase II Multicenter Trial of Anti-BCMA CAR T-Cell Therapy for MM Patients With Sub-Optimal Response After Auto HCT and Maintenance Len. BMTCTN1902
This study is designed as a Phase II, multicenter, single arm trial to assess anti-B Cell Maturation Antigen (BCMA) chimeric antigen receptor (CAR) T-cells (bb2121) to improve post autologous hematopoietic cell transplant (HCT) responses among patients with multiple myeloma (MM).
Read the detailed description
After meeting the eligibility criteria and enrolling on the trial, patients will undergo leukapheresis for collection of autologous lymphocytes, which will be sent to BMS/Celgene manufacturing facilities. Once cells have been manufactured, patients will then proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m^2 and fludarabine 30mg/m^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression
- Conditions
- Multiple Myeloma
- Being tested
- Lenalidomide, bb2121, Cyclophosphamide, Fludarabine, leukapheresis
- Keywords
- Multiple Myeloma, CAR T-cells, Anti-Myeloma Agents, lenalidomide, Maintenance Therapy, Hematologic Disorders, Infusion
- Medical subject headings
- Multiple Myeloma, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Also called Revlimid
Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121Biological
Also called ide-cel
Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10^6 cells.
CyclophosphamideDrug
300 mg/m^2/day for 3 consecutive days prior to the CAR T infusion
FludarabineDrug
30 mg/m^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresisProcedure or surgery
Placement of central line catheter and leukapheresis
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide and bb2121 | Experimental | Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m^2 and fludarabine 30mg/m^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression. Receives: Drug: Lenalidomide; Biological: bb2121; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: leukapheresis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of BCMA CAR-T Cell Therapy
Achieving a complete response or better (CR or sCR) as assessed by the 6-month time point after BCMA CAR T-cell therapy in MM patients with suboptimal disease responses after an autologous HCT and lenalidomide maintenance.
Measured: 6 months
Secondary outcomes (7)
Cumulative Incidence of Disease Progression
Diseases will be assessed by response categories based on the International Myeloma Working Group: Stringent Complete Response (sCR), Complete Remission (CR), Very Good Partial Remission (VGPR), Partial Remission (PR), Minimal Response (MR), Stable Disease (SD).
Measured: 1 Year
Proportion of Patients Achieving an Upgrade in Response Based on Their Best Disease Response
Proportion of patients achieving upgrade in response following enrollment (SD to MR or greater, MR to PR or greater, or PR to VGPR or greater) and Conversion to MRD negativity. MRD will be assessed by multi-color flow at 10-5 level
Measured: 1 Year
Number of Participants With Non Relapse Mortality
Non-Relapse Mortality (NRM) is defined as death occurring in a patient from causes other than disease relapse or progression. Disease progression is the competing event for NRM.
Measured: 1 Year
Kaplan-Meier of Progression Free Survival
Defined as progression of disease or death from any cause. Surviving patients without disease progression will be censored at the date of last contact.
Measured: 1 Year
Incidence of Cytokine Release Syndrome (CRS)
Overall incidence of CRS of any grade and grade 3 or 4 CRS post CAR T-cell infusion will be reported on all patients.
Measured: Day 4, Day 7, Day 10, Day 14, and Day 21 post-infusion
Incidence of Prolonged Cytopenias
Overall incidence of prolonged cytopenias will be reported. Prolonged cytopenia is defined as failure to achieve ANC greater than 500/mm3 or platelet count greater than 20,000/mm3(with or without support) by 30 days post CAR T-cell infusion.
Measured: 1 Year
Incidence of Neurotoxicity
Overall incidence of CAR T-cell related neurotoxicity per the ASBMT immune effector cell associated neurotoxicity syndrome (ICANS) Consensus Grading.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2021
- Study start5 Jan 2022
- Primary completion22 Aug 2024
- Study completion20 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Assess anti-B Cell Maturation Antigen(BCMA) chimeric antigen receptor (CAR) T-cells (bb2121) to improve post autologous hematopoietic cell transplant (HCT) responses among patients with multiple myeloma (MM).
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Blood and Marrow Transplant Clinical Trials Network, National Cancer Institute (NCI), National Marrow Donor Program, Celgene a wholly owned subsidiary of BMS
- Responsible party
- Sponsor
- Investigators
- Marcelo C Pasquini, MD, MS, Study director, Medical College of WisconsinAlfred Garfall, MD, Principal investigator, University of PennsylvanniaSergio Giralt, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05032820
- Sponsor's protocol ID
- BMTCTN1902
- Other IDs
- 2U10HL069294-11, 5U24CA076518
- Status last verified
- May 2026
- First submitted
- 8 Jul 2021
- Last updated
- 19 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc., where indicated).