Multiple Myeloma Clinical Trial

Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

Summary

This is a multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of bb2121 versus standard regimens in subjects with relapsed and refractory multiple myeloma (RRMM).

The study is anticipated to randomize approximately 381 subjects with RRMM. Approximately 254 subjects will be randomized to Treatment Arm A and approximately 127 subjects will be randomized to Treatment Arm B.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
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.

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
Subject has received at least 2 but no greater than 4 prior MM regimens.
Subject has received prior treatment with DARA, a proteasome inhibitor- and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles.
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.
Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen.
Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 peripheral neuropathy.
Adequate vascular access for leukapheresis

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.

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.

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:

Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
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.
Subject has any condition that confounds the ability to interpret data from the study.
Subject has nonsecretory multiple myeloma (MM).

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)

Subject has inadequate pulmonary function defined as oxygen saturation (SaO2) < 92% on room air.

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
Subject has active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome or amyloidosis.
Subject with known central nervous system (CNS) involvement with myeloma.
Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation.
Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal.
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.
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.
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.
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.
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.
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.
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.
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.
Subject has received autologous stem cell transplantation (ASCT) within 12 weeks prior to randomization.

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

Echocardiogram (ECHO) or multigated acquisition (MUGA) with left ventricular ejection fraction (LVEF) < 45%.
Ongoing treatment with chronic immunosuppressants (eg, cyclosporine or systemic steroids at any dose). Intermittent topical, inhaled or intranasal corticosteroids are allowed.
Subject is positive for human immunodeficiency virus (HIV-1 and HIV-2), chronic or active hepatitis B or active hepatitis A or C.
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.
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.
Hypersensitivity to DARA, thalidomide, lenalidomide, POM, BTZ, IXA, CFZ, ELO or dexamathasone. This includes rash ≥ Grade 3 during prior thalidomide, POM or lenalidomide therapy.
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.
Subject is a female who is pregnant, nursing, or breastfeeding
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.

Study is for people with:

Multiple Myeloma

Phase:

Phase 3

Estimated Enrollment:

381

Study ID:

NCT03651128

Recruitment Status:

Recruiting

Sponsor:

Celgene

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There are 59 Locations for this study

See Locations Near You

Local Institution - 109
Birmingham Alabama, 10016, United States
University of Alabama Birmingham
Birmingham Alabama, 10016, United States
Local Institution - 141
Scottsdale Arizona, 85259, United States
Mayo Clinic Arizona
Scottsdale Arizona, 85259, United States
Local Institution - 145
Los Angeles California, 90048, United States
Local Institution - 122
Los Angeles California, 90095, United States
UCLA Medical Centre-Santa Monica Hematology and Oncology
Los Angeles California, 90095, United States
Local Institution - 124
Palo Alto California, 94304, United States
Local Institution - 142
Aurora Colorado, 80045, United States
University of Colorado Anschutz Cancer Pavilion
Aurora Colorado, 80045, United States
Local Institution - 108
Jacksonville Florida, 32224, United States
Mayo Clinic - Jacksonville
Jacksonville Florida, 32224, United States
Local Institution - 102
Tampa Florida, 33612, United States
Moffit Cancer Center
Tampa Florida, 33612, United States
Emory University Hospital
Atlanta Georgia, 30322, United States
Local Institution - 131
Atlanta Georgia, 30322, United States
Blood and Marrow Transplant Group of Georgia
Atlanta Georgia, 30342, United States
Local Institution - 140
Atlanta Georgia, 30342, United States
Local Institution - 139
Chicago Illinois, 60611, United States
Northwestern University Feinberg School of Medicine
Chicago Illinois, 60611, United States
Indiana University Cancer Center
Indianapolis Indiana, 46202, United States
Local Institution - 100
Indianapolis Indiana, 46202, United States
Local Institution - 112
Westwood Kansas, 66205, United States
The University of Kansas Hospital
Westwood Kansas, 66205, United States
Greenebaum University of Maryland
Baltimore Maryland, 21201, United States
Local Institution - 104
Baltimore Maryland, 21201, United States
Local Institution - 134
Boston Massachusetts, 02114, United States
Mass General
Boston Massachusetts, 02114, United States
Dana Farber Cancer Institute (DFCI)
Boston Massachusetts, 02215, United States
Local Institution - 123
Boston Massachusetts, 02215, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor Michigan, 48109, United States
Local Institution - 125
Rochester Minnesota, 55905, United States
Mayo Clinic - Rochester
Rochester Minnesota, 55905, United States
Local Institution - 114
Saint Louis Missouri, 63110, United States
Washington University School of Medicine, Siteman Cancer Center
Saint Louis Missouri, 63110, United States
Hackensack University Medical Center
Hackensack New Jersey, 07601, United States
Local Institution - 138
Hackensack New Jersey, 07601, United States
Local Institution - 119
New York New York, 10029, United States
Mount Sinai Medical Center
New York New York, 10029, United States
Local Institution - 115
New York New York, 10065, United States
Local Institution - 135
New York New York, 10065, United States
New York Presbyterian Hospital Weil Cornell Medical College
New York New York, 10065, United States
Duke Clinical Research Institute Duke University School of Medicine
Durham North Carolina, 27705, United States
Local Institution - 113
Durham North Carolina, 27705, United States
Local Institution - 111
Philadelphia Pennsylvania, 19107, United States
Thomas Jefferson University
Philadelphia Pennsylvania, 19107, United States
Fox Chase Cancer Center
Philadelphia Pennsylvania, 19111, United States
Local Institution - 110
Philadelphia Pennsylvania, 19111, United States
University of Pittsburgh Medical Center - William M. Cooper Ambulatory Care Pavilion
Pittsburgh Pennsylvania, 15232, United States
University of Pittsburgh Medical Center William M. Cooper Ambulatory Care Pavillion
Pittsburgh Pennsylvania, 15232, United States
Sarah Cannon Research Institute Center for Blood
Nashville Tennessee, 37203, United States
Local Institution - 106
Nashville Tennessee, 37203, United States
Baylor University Medical Center at Dallas
Dallas Texas, 75246, United States
Local Institution - 118
Dallas Texas, 75246, United States
Local Institution - 103
Dallas Texas, 75390, United States
Local Institution - 132
Houston Texas, 77030, United States
MD Anderson Cancer center
Houston Texas, 77030, United States
Local Institution - 136
Salt Lake City Utah, 84112, United States
University of Utah Huntsman Cancer Center
Salt Lake City Utah, 84112, United States
Local Institution - 105
Seattle Washington, 98104, United States
Swedish Cancer Institute
Seattle Washington, 98104, United States
Local Institution - 107
Madison Wisconsin, 53792, United States
University of Wisconsin Carbone Cancer Center
Madison Wisconsin, 53792, United States
Local Institution - 202
Leuven , 3000, Belgium
UZ Leuven
Leuven , 3000, Belgium
Local Institution - 302
Calgary Alberta, T2N 4, Canada
Tom Baker Cancer center
Calgary Alberta, T2N 4, Canada
Local Institution - 303
Toronto Ontario, M5G 2, Canada
Princess Margaret Cancer Centre
Toronto Ontario, M5G 2, Canada
CHRU Lille
Lille Cedex , 59037, France
Local Institution - 402
Lille Cedex , 59037, France
Centre Hospitalier Univ De Nantes Hotel-Dieu
Nantes , 44093, France
Local Institution - 403
Nantes , 44093, France
Hospital Saint-Louis - APHP
Paris , 75010, France
Local Institution - 400
Paris , 75010, France
IUCT Oncopole
Toulouse CEDEX 9 , 31059, France
Local Institution - 401
Toulouse CEDEX 9 , 31059, France
Local Institution - 513
Dusseldorf , 40225, Germany
Local Institution - 514
Hamburg , 20246, Germany
Local Institution - 512
Heidelberg , 69120, Germany
Medizinische Universitaetsklinik Heidelberg
Heidelberg , 69120, Germany
Local Institution - 515
Köln , 50937, Germany
Universitat zu Koln
Köln , 50937, Germany
Local Institution - 511
Würzburg , 97080, Germany
Universitaetsklinikum Wuerzburg
Würzburg , 97080, Germany
Azienda Ospedaliero Universitaria di Bologna - Policlinico S. Orsola-Malpighi - Istituto di Ematolog
Bologna , 40138, Italy
Local Institution - 611
Bologna , 40138, Italy
Local Institution - 806
Bunkyo-ku , 113-8, Japan
Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
Bunkyo-ku , 113-8, Japan
Local Institution - 804
Isehara City, Kanagawa , 259-1, Japan
Tokai University Hospital
Isehara, Kanagawa , 259-1, Japan
Local Institution - 807
Nagoya , 467-8, Japan
Japan Red Cross Medical Center
Shibuya-ku , 150-8, Japan
Local Institution - 805
Shibuya-ku , 150-8, Japan
Local Institution - 650
Amsterdam , 1081 , Netherlands
Erasmus Medical Center
Rotterdam , 3015 , Netherlands
Local Institution - 651
Rotterdam , 3015 , Netherlands
Oslo universitetssykehus, Rikshospitalet
Oslo Universitetssykehus, Rikshospitalet , N-002, Norway
Local Institution - 700
Oslo , N-002, Norway
Clinica Universidad de Navarra
Pamplona , 31008, Spain
Local Institution - 750
Pamplona , 31008, Spain
Hospital Universitario de Salamanca
Salamanca , 37007, Spain
Local Institution - 751
Salamanca , 37007, Spain
Karolinska Universitetssjukhuset - Huddinge
Stockholm , SE-14, Sweden
Local Institution - 800
Stockholm , SE-14, Sweden
Local Institution - 251
Bern , 3010, Switzerland
Universitaetsspital Bern - Inselspital
Bern , 3010, Switzerland
Local Institution - 850
Leeds , LS9 7, United Kingdom
Kings College Hospital
London , SE5 9, United Kingdom
Local Institution - 851
London , SE5 9, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Multiple Myeloma

Phase:

Phase 3

Estimated Enrollment:

381

Study ID:

NCT03651128

Recruitment Status:

Recruiting

Sponsor:


Celgene

How clear is this clinincal trial information?

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