Study of bb2121 in Multiple Myeloma

Sponsor

Celgene (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02658929

Collaborator

bluebird bio (Industry)

Enrollment

Locations

Arm

84.3

Anticipated Duration (Months)

7.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study CRB-401 is a 2-part, non-randomized, open label, multi-site Phase 1 study of bb2121 in adults with relapsed/refractory multiple myeloma (MM).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Biological: bb2121	Phase 1

Detailed Description

This is a 2-part, non-randomized, open label, multi-site Phase 1 study. the study design consists of 2 parts: Part A (Dose Escalation), in which the RP2D is determined, and Part B (Expansion Cohorts), in which subjects are treated with the determined RP2D.

Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (bb2121). Following manufacture of the drug product, subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide prior to bb2121 infusion. All subjects who have received bb2121 infusion will be followed for up to 60 months on CRB-401.

All subjects who complete the study, as well as those who withdraw from the study after receiving bb2121 for reasons other than death or meeting the early termination criteria, will be asked to continue to undergo long-term follow-up in a companion study for up to 15 years after their last bb2121 infusion, with a focus on long-term safety and efficacy.

Study Design

Study Type:

Interventional

Actual Enrollment :

67 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

CRB-401 A Phase 1 Study of bb2121 in BCMA-Expressing Multiple Myeloma

Actual Study Start Date :

Dec 22, 2015

Actual Primary Completion Date :

Jul 22, 2019

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bb2121 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	Biological: bb2121 bb2121

Arm

Intervention/Treatment

Experimental: bb2121

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

Biological: bb2121

bb2121

Outcome Measures

Primary Outcome Measures

Incidence of adverse events (AEs) and abnormal laboratory test results, including dose limiting toxicities (DLTs) [Day 1 through Month 60]

Secondary Outcome Measures

Disease-specific response criteria including: overall response rate (ORR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for MM. [Day 1 through Month 60]
Percentage of subjects who achieved a CR, VGR, PR according to IMWG Uniform Response Criteria for Multiple Myeloma (MM).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18 years of age at the time of signing informed consent
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Subjects must have measurable disease including at least one of the criteria below:

Serum M-protein greater or equal to 0.5 g/dL Urine M-protein greater or equal to 200 mg/24 h Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal -Women of child-bearing potential (WCBP) must have a negative serum pregnancy test prior to treatment and refrain from tissue donation including egg donation or any other tissue/blood/organ donations, for at least 1 year following bb2121 infusion. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study. All sexually active males subjects must refrain from tissue donation including egg donation or any other tissue/blood/organ donations, for at least 1 year following bb2121 infusion.

Part A:

Diagnosis of MM with relapsed or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor (e.g., bortezomib or carfilzomib) and immunomodulatory therapy (IMiD; e.g., lenalidomide or pomalidomide), or have "double refractory" disease to a proteasome inhibitor and IMiD, defined as progression on or within 60 days of treatment with these agents

Part B: Diagnosis of MM with relapsed or refractory disease with previous exposure to PI (e.g., bortezomib or carfilzomib), IMiDs (e.g., lenalidomide or pomalidomide), and daratumumab, and refractory (based on IMWG criteria) to their last line of therapy

Exclusion Criteria:

Subjects with known central nervous system disease
Inadequate hepatic function
Inadequate renal function
Inadequate bone marrow function
Presence of active infection within 72 hours
Significant co-morbid condition or disease which in the judgment of the Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditions
Subjects with second malignancies in addition to myeloma if the second malignancy has required therapy in the last 3 years or is not in complete remission
Subjects with a history of class III or IV congestive heart failure or non-ischemic cardiomyopathy, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the previous 6 months
Known human immunodeficiency virus (HIV) positivity
Subjects who have plasma cell leukemia or clinically significant amyloidosis
Pregnant or lactating women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Center	Stanford	California	United States	94305
2	National Cancer Institute	Bethesda	Maryland	United States	20892
3	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
4	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
5	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	Mayo Clinic	Rochester	Minnesota	United States	55905
7	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
8	Mt. Sinai Medical Center Division of Hematology/Oncology	New York	New York	United States	10029
9	Sarah Cannon Research Inst	Nashville	Tennessee	United States	37203