A Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (NDMM)

NCT04196491 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: BB2121-MM-004U1111-1243-5088
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 22

Brief Summary

This is a multicenter, open-label, phase 1, single arm study intended to determine the optimal target dose and safety of bb2121 in subjects with HR (R-ISS Stage III per IMWG criteria) NDMM. Subjects should have received 3 Cycles of standard induction therapy prior to undergoing leukapheresis procedure to collect autologous mononuclear cells for manufacture of the drug product (bb2121). Following manufacture of the drug product, subjects will receive fourth cycle of induction therapy followed by lymphodepleting therapy with fludarabine and cyclophosphamide prior to bb2121 infusion. Maintenance therapy is recommended for all subjects who have received bb2121 infusion and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Newly diagnosed multiple myeloma; BB2121; KarMMa-4; Phase I; NDMM; High Risk; R-ISS III; KRd; RVd; Dara-KRd; Dara-RVd; CyBorD; BCMA

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT) rates

  DLTs will be assessed during the DLT interval (ie, within 21 days immediately after bb2121 infusion). DLTs are defined as any bb2121 related Grade 3 to 5 toxicity.

  Up to completion of DLT period after last subject bb2121 infused

• Adverse Events (AEs)

  An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.

  Approximately 2 years after last subject bb2121 infused

Secondary Outcomes (11)

• Proportion of subjects who achieved Complete Response (CR) Rate

  Approximately 2 years after last subject bb2121 infused

• Overall Response Rate (ORR)

  Approximately 2 years after last subject bb2121 infused

• Duration of Response (DoR)

  Approximately 2 years after last subject bb2121 infused

• Time to Complete Response (TCR)

  Approximately 2 years after last subject bb2121 infused

• Time to start maintenance

  Approximately 2 years after last subject bb2121 infused

Study Arms (1)

Dose Escalation

EXPERIMENTAL

* bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 800 x 10\^6 CAR+ T cells after receiving lymphodepleting chemotherapy with a planned starting dose of 450 x 10\^6 CAR+ T cells. * Lenalidomide maintenance therapy is recommended for all patients and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later

Biological: bb2121; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Lenalidomide

Interventions

bb2121 BIOLOGICAL

CAR-T Cell Therapy

Also known as: ide-cel

Dose Escalation

Fludarabine DRUG

Lymphodepleting Chemotherapy

Dose Escalation

Cyclophosphamide DRUG

Lymphodepleting Chemotherapy

Dose Escalation

Lenalidomide DRUG

Maintenance Therapy

Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy all of the following criteria to be enrolled in the study:
• Subject is newly diagnosed and has symptomatic Multiple Myeloma (MM) prior to initiating induction anti-myeloma therapy
• Subject is ≥ 18 years of age at the time of initial diagnosis of MM
• Subject has measurable disease at initial diagnosis by
• M-protein and/or
• Light chain MM without measurable disease in the serum or urine
• Subject has high-risk MM at the time of initial diagnosis of MM per R-ISS Stage III as defined by IMWG:
• ISS Stage III and cytogenetic abnormalities with t(4; 14) and/or del(17p); and/or t(14:16) by iFISH; or;
• ISS Stage III and serum LDH \> ULN
• Subject has Eastern Cooperative Oncology Group performance ≤ 1
• Subjects has received ≤ to 3 cycles of the following induction anti-myeloma therapy prior to enrollment:
• Cycle 1: one of the following regimens (RVd, KRd, CyBorD, D-RVd and D-KRd)
• Cycle 2 to Cycle 3: either KRd or RVd (Cycle 3 must be without dexamethasone)

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment: The presence of any of the following will exclude a subject from enrollment:
• At initial diagnosis, screening and prior to initiation of induction therapy for MM:
• Subject has non-secretory MM
• During Screening:
• Subject received any treatments for MM other than up to 3 cycles of induction therapy per protocol
• Subject has any of the following laboratory abnormalities:
• Absolute neutrophil count \< 1,000/μL
• Platelet count \< 50,000 mm3
• Hemoglobin \< 8 g/dL (\< 4.9 mmol/L)
• Serum creatinine clearance \< 45 mL/min
• Corrected serum calcium \> 13.5 mg/dL (\> 3.4 mmol/L)
• Serum aspartate aminotransferase or alanine aminotransferase \> 2.5 × upper limit of normal
• Serum total bilirubin \> 1.5 × ULN or \> 3.0 mg/dL for subjects with documented Gilbert's syndrome
• INR or aPTT \> 1.5 × ULN
• Subject has history or presence of clinically significant CNS pathology

Sponsors & Collaborators

• Celgene: lead

Study Sites (22)

Local Institution - 119

Phoenix, Arizona, 85054, United States

Location

Local Institution - 110

Los Angeles, California, 90095, United States

Location

Local Institution - 116

San Francisco, California, 94143, United States

Location

Local Institution - 106

Denver, Colorado, 80218, United States

Location

Local Institution - 101

Jacksonville, Florida, 32224, United States

Location

Local Institution - 113

Tampa, Florida, 33612, United States

Location

Local Institution - 108

Atlanta, Georgia, 30322, United States

Location

Local Institution - 123

Atlanta, Georgia, 30342, United States

Location

Local Institution - 115

Boston, Massachusetts, 02114, United States

Location

Local Institution - 122

Boston, Massachusetts, 02215, United States

Location

Local Institution - 117

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 121

New York, New York, 10016, United States

Location

Local Institution - 109

New York, New York, 10029, United States

Location

Local Institution - 124

New York, New York, 10065, United States

Location

Local Institution - 120

Charlotte, North Carolina, 28207, United States

Location

Local Institution - 112

Portland, Oregon, 97239, United States

Location

Local Institution - 118

Philadelphia, Pennsylvania, 19104, United States

Location

Local Institution - 103

Nashville, Tennessee, 37203, United States

Location

Local Institution - 102

Dallas, Texas, 75390, United States

Location

Local Institution - 114

Houston, Texas, 77030, United States

Location

Local Institution - 104

Seattle, Washington, 98109-1024, United States

Location

Local Institution - 107

Milwaukee, Wisconsin, 53226-3522, United States

Location

Related Publications (1)

• Parmar H, Vesole DH, Biran N. From VAD to VRD: Is Transplant Still Needed in the Upfront Setting of Myeloma? Cancer J. 2021 May-Jun 01;27(3):190-195. doi: 10.1097/PPO.0000000000000522.

  PMID: 34549906 DERIVED

Related Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Multiple Myeloma

Interventions

idecabtagene vicleucel; fludarabine; Cyclophosphamide; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2019
• First Posted: December 12, 2019
• Study Start: May 27, 2020
• Primary Completion: June 7, 2023
• Study Completion: June 7, 2023
• Last Updated: August 23, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (22)