Study of bb21217 in Multiple Myeloma

Study Overview
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Brief Summary
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Study CRB-402 is a 2-part, non-randomized, open label, multi-site Phase 1 study of bb21217 in adults with relapsed/refractory multiple myeloma (MM).

Detailed Description
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Part A of the study will be Dose Escalation followed by Part B, an expansion cohort. Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (bb21217). Following manufacture of the drug product, subjects will receive lymphodepletion prior to bb21217 infusion. All subjects will then be followed for up to 60 months in Study CRB-402. All subjects who complete the study, as well as those who withdraw from the study after receiving bb21217 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.

Official Title
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A Phase 1 Study of bb21217, an Anti-BCMA CAR T Cell Drug Product, in Relapsed and/or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: bb21217


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age at the time of signing informed consent Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Diagnosis of MM with relapsed or refractory disease and have had at least 3 different prior lines of therapy with previous exposure to PI, IMiDs, and a CD38 antibody. Have undergone at least 2 consecutive cycles of treatment for each therapy, unless PD was the best response to the therapy. Refractory to their last line of therapy. Subjects must have measurable disease 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 Subjects with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control 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 Known human immunodeficiency virus (HIV) positivity Known hepatitis A virus (HAV), hepatitis B virus (HBV) or hepatitis C virus (HCV) positivity with evidence of ongoing infection. Pregnant or lactating women Previous history of an allogeneic bone marrow transplantation, treatment with any gene therapy based therapeutic for cancer, or BCMA-targeted therapy Inadequate pulmonary function defined as oxygen saturation (SaO2) <92% on room air Subjects who have a history of plasma cell leukemia, active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS, or clinically significant amyloidosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bb21217 Experimental Arm<br> | Biological: bb21217<br>* autologous T cells transduced ex-vivo with anti-BCMA CAR lentiviral vector encoding the chimeric antigen receptor (CAR) targeted to human BCMA, suspended in cryopreservative solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs), DLTs, and changes in laboratory results | Incidence of adverse events (AEs) and abnormal laboratory test results, including dose limiting toxicities (DLTs) | Day 1 through Month 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-specific response criteria | • Disease-specific response criteria including, but not limited to: complete response (CR), very good partial response (VGPR), and partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma | Month 1 through Month 60 |