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Engineered immune cells take on Hard-to-Treat myeloma in major trial

NCT ID NCT03651128

Disease control Sponsor: Celgene Source: ClinicalTrials.gov ↗

First seen Jun 26, 2026 · Last updated Jun 27, 2026 · Updated 1 time

Summary

This phase 3 trial tests whether a personalized cell therapy called bb2121 works better than standard drug combinations for people with relapsed and refractory multiple myeloma. About 386 participants were randomly assigned to receive either bb2121 or one of several standard regimens. The main goal is to see how long the cancer stays under control, with secondary goals including overall survival and side effects.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: bb2121 (a cell therapy made from the patient's own immune cells, engineered to attack myeloma cells)
What this could lead to: If successful, bb2121 could offer a more effective treatment option for people with multiple myeloma that has returned or stopped responding to standard therapies.
What could go wrong: This is an advanced phase 3 trial, but cell therapies can have serious side effects like cytokine release syndrome. The results may not apply to all patients, and long-term benefits are still being studied.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

386 people

The number who actually took part.

Started

Apr 2019

Finished

Apr 2026

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study: 1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF). 2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted. 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements within this protocol and for a subject randomized to Treatment Arm A, subject agrees to continued follow-up for up to 15 years as mandated by the regulatory guidelines for gene therapy trials. 4. Subject has documented diagnosis of MM and 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 (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio 5. Subject has received at least 2 but no greater than 4 prior MM regimens. 6. Subject has received prior treatment with DARA, a proteasome inhibitor- and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles. 7. Subject must be refractory to the last treatment regimen. Refractory is defined as documented progressive disease during or within 60 days (measured from the last dose of any drug within the regimen) of completing treatment with the last anti-myeloma regimen before study entry. 8. Subject achieved a response (minimal response \[MR\] or better) to at least 1 prior treatment regimen. 9. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 10. Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 peripheral neuropathy. 11. Adequate vascular access for leukapheresis 12. Females of childbearing potential (FCBP) must: a. Have negative pregnancy test(s) as verified by the Investigator. This applies even if the subject practices true abstinence from heterosexual contact. b. Either practice true abstinence from heterosexual contact or agree to use, and be able to comply with, effective measures of contraception without interruption. c. Agree to abstain from breastfeeding during study participation. d. Refrain from tissue donation including egg cell donation or any other tissue/blood/organ donations. 13. Male subjects must: a. Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, even if he has undergone a successful vasectomy. b. Refrain from tissue donation including sperm or any other tissue/blood/organ donations. 14. Only subjects that would be considered for any of the 5 proposed standard regimens (DPd, DVd, IRd, Kd, or EPd), as judged by the investigator, should be included in the study. Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment: 1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 3. Subject has any condition that confounds the ability to interpret data from the study. 4. Subject has nonsecretory multiple myeloma (MM). 5. Subject has any of the following laboratory abnormalities: a. Absolute neutrophil count (ANC) \< 1,000/μL b. Platelet count: \< 75,000/μL in subjects in whom \< 50% of bone marrow nucleated cells are plasma cells and platelet count \< 50,000/μL in subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells (it is not permissible to transfuse a subject to reach this level) c. Hemoglobin \< 8 g/dL (\< 4.9 mmol/L) (it is not permissible to transfuse a subject to reach this level) d. Serum creatinine clearance (CrCl) \< 45 mL/min e. Corrected serum calcium \> 13.5 mg/dL (\> 3.4 mmol/L) f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 × upper limit of normal (ULN) g. Serum total bilirubin \> 1.5 × ULN or \> 3.0 mg/dL for subjects with documented Gilbert's syndrome h. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) \> 1.5 × ULN, or history of Grade ≥ 2 hemorrhage within 30 days, or subject requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors) 6. Subject has inadequate pulmonary function defined as oxygen saturation (SaO2) \< 92% on room air. 7. Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years • Basal cell carcinoma of the skin • Squamous cell carcinoma of the skin * Carcinoma in situ of the cervix * Carcinoma in situ of the breast * Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis \[TNM\] clinical staging system) or prostate cancer that can be treated with curative intent 8. Subject has active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome or amyloidosis. 9. Subject with known central nervous system (CNS) involvement with myeloma. 10. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation. 11. Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal. 12. Subject has a 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. Subject was treated with DARA in combination with POM with or without dex (DP±d) as part of their most recent anti-myeloma treatment regimen, cannot receive DPd as bridging therapy but may receive DVd, IRd, Kd or EPdas bridging as per Investigator's discretion if randomized to Treatment Arm A. 14. Subject was treated with DP±d as part of their most recent anti-myeloma treatment regimen, cannot receive DPd if randomized to Treatment Arm B but may receive DVd, IRd, Kd, or EPd as per Investigator's discretion. 15. Subject was treated with DARA in combination with BTZ with or without dexamethasone (DV±d) as part of their most recent anti-myeloma treatment regimen, cannot receive DVd as bridging therapy but may receive DPd, IRd, Kd, or EPd as bridging as per Investigator's discretion if randomized to Treatment Arm A. 16. Subject was treated with DV±d as part of their most recent anti-myeloma treatment regimen, cannot receive DVd if randomized to Treatment Arm B but may receive DPd, IRd, Kd, or EPd as per Investigator's discretion. 17. Subject was treated with IXA in combination with LEN with or without dexamethasone (IR±d) as part of their most recent anti-myeloma treatment regimen, cannot receive IRd as bridging therapy but may receive DPd, DVd, Kd, or EPd as bridging as per Investigator's discretion if randomized to Treatment Arm A. 18. Subject was treated with IR±d as part of their most recent anti-myeloma treatment regimen, cannot receive IRd if randomized to Treatment Arm B but may receive DPd, DVd, Kd, or EPd as per Investigator's discretion. 19. Previous history of an allogeneic hematopoietic stem cell transplantation, treatment with any gene therapy-based therapeutic for cancer, investigational cellular therapy for cancer or BCMA targeted therapy. 20. Subject has received autologous stem cell transplantation (ASCT) within 12 weeks prior to randomization. 21. Subject has received any of the following within the last 14 days prior to randomization: a. Plasmapheresis b. Major surgery (as defined by the Investigator) c. Radiation therapy other than local therapy for myeloma-associated bone lesions d. Use of any investigational agents and systemic anti-myeloma drug therapy 22. Echocardiogram (ECHO) or multigated acquisition (MUGA) with left ventricular ejection fraction (LVEF) \< 45%. 23. Ongoing treatment with chronic immunosuppressants (eg, cyclosporine or systemic steroids at any dose). Intermittent topical, inhaled or intranasal corticosteroids are allowed. 24. Subject is positive for human immunodeficiency virus (HIV-1 and HIV-2), chronic or active hepatitis B or active hepatitis A or C. 25. Subject has uncontrolled systemic fungal, bacterial, viral or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antimicrobial treatment) or requiring IV antimicrobials for management. 26. Subject has 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 randomization. 27. Hypersensitivity to DARA, thalidomide, lenalidomide, POM, BTZ, IXA, CFZ, ELO or dexamathasone. This includes rash ≥ Grade 3 during prior thalidomide, POM or lenalidomide therapy. 28. Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab or hypersensitivity to the excipients contained in the formulation of DARA, POM, LEN, IXA, BTZ, CFZ, ELO or dexamethasone. 29. Subject is a female who is pregnant, nursing, or breastfeeding 30. For a subject randomized to Treatment Arm B and will be on a POM- or LEN-containing regimen; unable or unwilling to undergo protocol required thromboembolism prophylaxis. 28 Subject is intolerant to bortezomib, or has acute diffuse infiltrative pulmonary and pericardial disease, subject cannot receive DVd as bridging therapy if randomized to Treatment Arm A or cannot receive DVd if randomized to Treatment Arm B. 31\. Subject was treated with K±d as part of their most recent anti-myeloma treatment regimen, cannot receive Kd if randomized to Treatment Arm B but may receive DPd, DVd, IRd or EPd as per Investigator's discretion. 32\. Subject was treated with EP±d as part of their most recent anti-myeloma treatment regimen, cannot receive EPd if randomized to Treatment Arm B but may receive DPd, DVd, Kd or IRd as per Investigator's discretion.

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Conditions

The condition(s) this trial relates to.

plasma cell myeloma Recurrence refractory plasma cell neoplasm

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Multiple myeloma

Contacts and locations

Locations

Froedtert Hospital BMT Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States
Local Institution - 100

Indianapolis, Indiana, 46202-528, United States
Local Institution - 101

Pittsburgh, Pennsylvania, 15232, United States
Local Institution - 102

Tampa, Florida, 33612, United States
Local Institution - 103

Dallas, Texas, 75390, United States
Local Institution - 104

Baltimore, Maryland, 21201-1595, United States
Local Institution - 105

Seattle, Washington, 98104, United States
Local Institution - 106

Nashville, Tennessee, 37203, United States
Local Institution - 107

Madison, Wisconsin, 53792, United States
Local Institution - 108

Jacksonville, Florida, 32224, United States
Local Institution - 109

Birmingham, Alabama, 10016, United States
Local Institution - 110

Philadelphia, Pennsylvania, 19111, United States
Local Institution - 111

Philadelphia, Pennsylvania, 19107, United States
Local Institution - 112

Westwood, Kansas, 66205-2003, United States
Local Institution - 113

Durham, North Carolina, 27705, United States
Local Institution - 114

St Louis, Missouri, 63110, United States
Local Institution - 115

New York, New York, 10065, United States
Local Institution - 118

Dallas, Texas, 75246, United States
Local Institution - 119

New York, New York, 10029, United States
Local Institution - 120

Ann Arbor, Michigan, 48109-5936, United States
Local Institution - 122

Los Angeles, California, 90095, United States
Local Institution - 123

Boston, Massachusetts, 02215, United States
Local Institution - 124

Palo Alto, California, 94304, United States
Local Institution - 125

Rochester, Minnesota, 55905-0001, United States
Local Institution - 131

Atlanta, Georgia, 30322, United States
Local Institution - 132

Houston, Texas, 77030, United States
Local Institution - 134

Boston, Massachusetts, 02114, United States
Local Institution - 135

New York, New York, 10065, United States
Local Institution - 136

Salt Lake City, Utah, 84112, United States
Local Institution - 138

Hackensack, New Jersey, 07601, United States
Local Institution - 139

Chicago, Illinois, 60611, United States
Local Institution - 140

Atlanta, Georgia, 30342, United States
Local Institution - 141

Scottsdale, Arizona, 85259, United States
Local Institution - 142

Aurora, Colorado, 80045, United States
Local Institution - 145

Los Angeles, California, 90048, United States
Local Institution - 202

Leuven, 3000, Belgium
Local Institution - 251

Bern, 3010, Switzerland
Local Institution - 302

Calgary, Alberta, T2N 4N2, Canada
Local Institution - 303

Toronto, Ontario, M5G 2M9, Canada
Local Institution - 400

Paris, 75010, France
Local Institution - 401

Toulouse, 31059, France
Local Institution - 402

Lille, 59037, France
Local Institution - 403

Nantes, 44093, France
Local Institution - 511

Würzburg, 97080, Germany
Local Institution - 512

Heidelberg, 69120, Germany
Local Institution - 513

Düsseldorf, 40225, Germany
Local Institution - 514

Hamburg, 20246, Germany
Local Institution - 515

Cologne, 50937, Germany
Local Institution - 611

Bologna, 40138, Italy
Local Institution - 650

Amsterdam, 1081 HV, Netherlands
Local Institution - 651

Rotterdam, 3015 CN, Netherlands
Local Institution - 700

Oslo, N-0027, Norway
Local Institution - 750

Pamplona, 31008, Spain
Local Institution - 751

Salamanca, 37007, Spain
Local Institution - 800

Stockholm, SE-141 86, Sweden
Local Institution - 804

Isehara City, Kanagawa, 259-1193, Japan
Local Institution - 805

Shibuya-ku, 150-8935, Japan
Local Institution - 806

Bunkyō City, 113-8677, Japan
Local Institution - 807

Nagoya, 467-8602, Japan
Local Institution - 850

Leeds, LS9 7TF, United Kingdom
Local Institution - 851

London, SE5 9RS, United Kingdom
University Of Nebraska

Omaha, Nebraska, 68198-7680, United States

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