Study of bb21217 in Multiple Myeloma

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

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).

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: bb21217

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF Medical Center at Parnassus
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Insitute, Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02144
      • Massachusetts General Hospital Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center At Hackensack UMC
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bb21217 Experimental Arm	Biological: bb21217; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: 2seventy bio
• Investigators: Study Director: Anna Truppel-Hartmann, MD, bluebird bio

Publications and helpful links

General Publications

• Madduri D, Parekh S, Campbell TB, Neumann F, Petrocca F, Jagannath S. Anti-BCMA CAR T administration in a relapsed and refractory multiple myeloma patient after COVID-19 infection: a case report. J Med Case Rep. 2021 Feb 19;15(1):90. doi: 10.1186/s13256-020-02598-0.

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2017
• Primary Completion (Actual): December 2, 2022
• Study Completion (Actual): December 2, 2022

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: September 5, 2017
• First Posted (Actual): September 6, 2017

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CRB-402

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No