An Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma

Study Purpose

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 181 subjects will be enrolled into one of two cohorts. Cohort 1 will enroll approximately 73 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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 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.
3. 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: - R-ISS stage III AND.
  • - 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. 4. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. 5. 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: 1. Subject used any investigational agents within 14 days of leukapheresis. 2. Subject received any of the following within the last 14 days of leukapheresis: 1. Plasmapheresis. 2. Major surgery (as defined by the investigator) 3. Radiation therapy other than local therapy for myeloma associated bone lesions. 4. Use of any systemic anti-myeloma drug therapy. 3. Subject with known central nervous system involvement with myeloma. 4. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation. 5. History or presence of clinically relevant central nervous system (CNS) pathology. 6. Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis. 7. 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. 8. Ongoing treatment with chronic immunosuppressants. 9. 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. 10. Subject has received ASCT within 12 weeks prior to leukapheresis. 11. Subject has history of primary immunodeficiency. 12. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C. 13. Subject has uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment. 14. Subject with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years. 15. Pregnant or lactating women. 16. Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03601078
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Celgene
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Lars Sternas, MD, PhD
Principal Investigator Affiliation Celgene
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries France, Germany, Italy, Spain, United Kingdom, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Additional Details

Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured for cohorts 1, 2a and 2b only.

Arms & Interventions

Arms

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

Interventions

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)

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Mayo Clinic Arizona, Scottsdale, Arizona

Status

Recruiting

Address

Mayo Clinic Arizona

Scottsdale, Arizona, 85259

UCSF Medical Center, San Francisco, California

Status

Recruiting

Address

UCSF Medical Center

San Francisco, California, 94142

Moffitt Cancer Center, Tampa, Florida

Status

Recruiting

Address

Moffitt Cancer Center

Tampa, Florida, 33612

Emory University, Atlanta, Georgia

Status

Recruiting

Address

Emory University

Atlanta, Georgia, 30322

Massachusetts General Hospital, Boston, Massachusetts

Status

Recruiting

Address

Massachusetts General Hospital

Boston, Massachusetts, 02117

Dana Farber Cancer Institute, Boston, Massachusetts

Status

Recruiting

Address

Dana Farber Cancer Institute

Boston, Massachusetts, 02215-5450

Beth Israel Deaconess Medical Center, Boston, Massachusetts

Status

Recruiting

Address

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

Washington University, Saint Louis, Missouri

Status

Recruiting

Address

Washington University

Saint Louis, Missouri, 63110

University of Nebraska, Omaha, Nebraska

Status

Recruiting

Address

University of Nebraska

Omaha, Nebraska, 68198-7680

Hackensack, New Jersey

Status

Recruiting

Address

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601

Mt Sinai Medical Center - NY, New York, New York

Status

Recruiting

Address

Mt Sinai Medical Center - NY

New York, New York, 10029

New York, New York

Status

Recruiting

Address

Columbia University Medical Center / New York Presbyterian Hospital

New York, New York, 10032

Memorial Sloan Kettering Cancer Center, New York, New York

Status

Not yet recruiting

Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Levine Cancer Institute, Charlotte, North Carolina

Status

Recruiting

Address

Levine Cancer Institute

Charlotte, North Carolina, 28204

Sarah Cannon Research Inst, Nashville, Tennessee

Status

Recruiting

Address

Sarah Cannon Research Inst

Nashville, Tennessee, 37203

Dallas, Texas

Status

Recruiting

Address

University of Texas Southwestern Medical Center

Dallas, Texas, 75235

Houston, Texas

Status

Recruiting

Address

MD Anderson Cancer Center The University of Texas

Houston, Texas, 77030

Swedish Cancer Inst, Seattle, Washington

Status

Recruiting

Address

Swedish Cancer Inst

Seattle, Washington, 98104

Milwaukee, Wisconsin

Status

Recruiting

Address

Froedtert Hospital BMT Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-3522

International Sites

CHU de Poitiers, Poitiers, France

Status

Recruiting

Address

CHU de Poitiers

Poitiers, , 86021

Universitaetsklinkum Hamburg-Eppendorf, Hamburg, Germany

Status

Recruiting

Address

Universitaetsklinkum Hamburg-Eppendorf

Hamburg, , 20246

Tuebingen, Germany

Status

Not yet recruiting

Address

University Hospital Tuebingen, Department of Internal Medicine

Tuebingen, , 72076

Universitatsklinikum Würzburg, Würzburg, Germany

Status

Recruiting

Address

Universitatsklinikum Würzburg

Würzburg, , 97080

Bologna, Italy

Status

Recruiting

Address

Azienda Ospedaliero Universitaria Di Bologna - Policlinico S.Orsola Malpighi

Bologna, , 40138

Clinica Universitaria de Navarra, Pamplona, Spain

Status

Recruiting

Address

Clinica Universitaria de Navarra

Pamplona, , 31008

Hospital Universitario de Salamanca, Salamanca, Spain

Status

Recruiting

Address

Hospital Universitario de Salamanca

Salamanca, , 37007

London, United Kingdom

Status

Recruiting

Address

King's College HospitalGKT School of Medicine

London, , SE5 9RS