Upfront Chimeric Antigen Receptor T-Cell to Upgrade Response in Multiple Myeloma

NCT ID: NCT05032820

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-05
• Study Completion Date: 2025-02-20

Brief 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).

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lenalidomide and bb2121

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.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

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

bb2121

Intervention Type: BIOLOGICAL

Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.

Cyclophosphamide

Intervention Type: DRUG

300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion

Fludarabine

Intervention Type: DRUG

30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion

leukapheresis

Intervention Type: PROCEDURE

Placement of central line catheter and leukapheresis

Interventions

Lenalidomide

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

Intervention Type: DRUG

bb2121

Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.

Intervention Type: BIOLOGICAL

Cyclophosphamide

300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion

Intervention Type: DRUG

Fludarabine

30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion

Intervention Type: DRUG

leukapheresis

Placement of central line catheter and leukapheresis

Intervention Type: PROCEDURE

Other Intervention Names

Revlimid; ide-cel

Eligibility Criteria

Inclusion Criteria

1. Age greater than or equal to 18.00 years

2. Patients must meet the criteria for symptomatic MM requiring therapy (Appendix A) prior to initiating initial systemic anti-myeloma treatment.

3. 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.

4. Patient must have additional stored stem cells greater than or equal to 2x10^6 CD34+ cells per kg actual body weight.

5. Patients must be less than or equal to 12 months after autologous HCT at the time of enrollment.

6. 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.

7. 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.

8. 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.

9. Patients must have Karnofsky performance greater than or equal to 70.

10. Patients must have recovered to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding Grade 2 neuropathy.

11. Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 without filgrastim use in the prior 14 days.

12. Platelet count greater than 100,000/mm^3 (without platelet transfusion in the previous 7 days or thrombopoietin mimetics in the previous 28 days).

13. Hemoglobin greater than 9 g/dL (without red blood cell transfusion in the previous 7 days).

14. Creatinine Clearance (CrCl) greater than or equal to 60 mL/min, measured or estimated by Cockcroft-Gault equation.

15. Corrected serum calcium less than or equal to 13.5 mg/dL.

16. Oxygen saturation greater than 92% on room air.

17. 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

18. International ratio (INR) or partial thromboplastin time (PTT) less than 1.5 x ULN

19. Cardiac Function: left ventricular ejection fraction greater than 45% by echocardiogram or MUGA.

20. 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.

21. 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.

22. 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.

Exclusion Criteria

1. Patients with a prior allogeneic hematopoietic cell.

2. 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).

3. Patients with disease progression (see Section 3.1.2 for disease progression definition) at any time prior to enrollment.

4. Patients receiving any of the following less than 14 days prior to enrollment:

1. Plasmapheresis

2. Major surgery (as defined by the investigator)

3. Radiation therapy other than local therapy for MM-associated bone lesions

4. Use of any systemic anti-myeloma drug therapy (with the exception of lenalidomide maintenance)

5. Any investigational agents

6. Corticosteroids (Physiologic replacement, topical, intranasal and inhaled steroids are permitted)

5. Patients with known Central Nervous System (CNS) involvement with MM.

6. Patients with a prior organ transplant requiring systemic immunosuppressive therapy.

7. Patients who previously experienced toxicities related to lenalidomide resulting in permanent treatment discontinuation.

8. Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with an immunomodulatory agent (IMiD).

9. Patients unwilling to take DVT prophylaxis while on lenalidomide maintenance.

10. Patients with history of greater than or equal to Grade 2 hemorrhage within 30 days of enrollment.

11. Patient requiring ongoing treatment with chronic, therapeutic dosing of anticoagulants (e.g. Warfarin, low molecular weight heparin, Factor Xa inhibitors).

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. Patients with previous history of treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy.

20. 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.

21. Female patients who are pregnant (positive beta-HCG), or breastfeeding, or who intend to become pregnant during participation in the study.

22. Patient with known allergy or hypersensitivity to any of the study medications, their analogues, or excipients in the various formulations of any agent.

23. Patient with serious medical of psychiatric illness likely to interfere with participation on this clinical study.

24. Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.

25. Patients unwilling or unable to provide informed consent 25. Patients unable or unwilling to return to the transplant center for treatment and follow up.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Blood and Marrow Transplant Clinical Trials Network

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Marrow Donor Program

OTHER

Sponsor Role: collaborator

Celgene a wholly owned subsidiary of BMS

UNKNOWN

Sponsor Role: collaborator

Marcelo Pasquini, MD

OTHER

Sponsor Role: lead

Responsible Party

Marcelo Pasquini, MD

Primary Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Marcelo C Pasquini, MD, MS

Role: STUDY_DIRECTOR

Medical College of Wisconsin

Alfred Garfall, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvannia

Sergio Giralt, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

City of Hope National Medical Center

Duarte, California, United States

Stanford Hospital and Clinics

Palo Alto, California, United States

University of California, San Francisco

San Francisco, California, United States

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Loyola University Medical Center

Maywood, Illinois, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Roswell Park Cancer Center

Buffalo, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Pennsylvania Hospital Center

Philadelphia, Pennsylvania, United States

Baylor College and Medicine

Houston, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

University of Wisconsin Hospitals and Clinics

Madison, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Informed Consent to Participate in Research

View Document

Document Type: Informed Consent Form: Pregnancy Partner Informed Consent Form

View Document

Related Links

https://bmtctn.net/

Blood and Marrow Transplant Clinical Trials Network Website

Other Identifiers

2U10HL069294-11

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5U24CA076518

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BMTCTN1902

Identifier Type: -

Identifier Source: org_study_id