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

Completed · Phase 2

Conditions studied: Multiple Myeloma

In brief

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).

Key facts

Study ID

NCT05032820

Run by

Medical College of Wisconsin

People needed

40

Starts

2022-01-05

Expected to finish

2025-02-20

Last updated by the study team

2026-05-19

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• 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.

You may not qualify if…

• 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.
• 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.

Where it is running

• 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

Full record on ClinicalTrials.gov

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