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

NCT ID: NCT04196491

Last Updated: 2023-08-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-27
• Study Completion Date: 2023-06-07

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation

• 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

Group Type: EXPERIMENTAL

bb2121

Intervention Type: BIOLOGICAL

CAR-T Cell Therapy

Fludarabine

Intervention Type: DRUG

Lymphodepleting Chemotherapy

Cyclophosphamide

Intervention Type: DRUG

Lymphodepleting Chemotherapy

Lenalidomide

Intervention Type: DRUG

Maintenance Therapy

Interventions

bb2121

CAR-T Cell Therapy

Intervention Type: BIOLOGICAL

Fludarabine

Lymphodepleting Chemotherapy

Intervention Type: DRUG

Cyclophosphamide

Lymphodepleting Chemotherapy

Intervention Type: DRUG

Lenalidomide

Maintenance Therapy

Intervention Type: DRUG

Other Intervention Names

ide-cel

Eligibility Criteria

Inclusion Criteria

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

1. Subject is newly diagnosed and has symptomatic Multiple Myeloma (MM) prior to initiating induction anti-myeloma therapy

2. Subject is ≥ 18 years of age at the time of initial diagnosis of MM

3. Subject has measurable disease at initial diagnosis by

• M-protein and/or
• Light chain MM without measurable disease in the serum or urine

4. 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

5. Subject has Eastern Cooperative Oncology Group performance ≤ 1

6. 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)

Exclusion Criteria

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:

1. Subject has non-secretory MM

During Screening:

2. Subject received any treatments for MM other than up to 3 cycles of induction therapy per protocol

3. Subject has any of the following laboratory abnormalities:

1. Absolute neutrophil count < 1,000/μL

2. Platelet count < 50,000 mm3

3. Hemoglobin < 8 g/dL (< 4.9 mmol/L)

4. Serum creatinine clearance < 45 mL/min

5. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)

6. Serum aspartate aminotransferase or alanine aminotransferase > 2.5 × upper limit of normal

7. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome

8. INR or aPTT > 1.5 × ULN

4. Subject has history or presence of clinically significant CNS pathology

5. Subjects has high risk for developing deep vein thrombosis or pulmonary embolus and are unable or unwilling to undergo anti-thrombotic therapy

6. Subject has peripheral neuropathy of > Grade 2 severity according to the NCI CTCAE Version 4.03 with bortezomib based induction regimen

7. Subjects has moderate or severe pulmonary hypertension

8. Subject has intolerance to components of induction regimen (KRd or RVd) or has any contraindication to one or the other drug

9. Subject has not recovered from induction therapy-related toxicities (non-hematologic) to < grade 1 CTCAE at the time of screening

10. Subject has prior history of deep vein thrombosis or pulmonary embolus (PE) within 6 months of starting study treatment

11. Subject has cardiac conditions such as:

1. Echocardiogram or multi gated acquisition assessment of left ventricular ejection fraction < 45%

2. Subject has a history of clinically significant cardiovascular disease or clinically significant ECG abnormalities

12. Subject has Pulmonary conditions such as:

1. Subject has known chronic obstructive pulmonary with a forced expiratory vol in 1 sec 50% of predicted normal.

2. Inadequate pulmonary function defined as oxygen saturation < 92 % on room air

13. Subject needs ongoing treatment with chronic immunosuppressants

14. Subject has history of primary immunodeficiency

15. Subject is seropositive for human immunodeficiency virus, chronic or active hepatitis B or active hepatitis A or C

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 119

Phoenix, Arizona, United States

Local Institution - 110

Los Angeles, California, United States

Local Institution - 116

San Francisco, California, United States

Local Institution - 106

Denver, Colorado, United States

Local Institution - 101

Jacksonville, Florida, United States

Local Institution - 113

Tampa, Florida, United States

Local Institution - 108

Atlanta, Georgia, United States

Local Institution - 123

Atlanta, Georgia, United States

Local Institution - 115

Boston, Massachusetts, United States

Local Institution - 122

Boston, Massachusetts, United States

Local Institution - 117

Hackensack, New Jersey, United States

Local Institution - 121

New York, New York, United States

Local Institution - 109

New York, New York, United States

Local Institution - 124

New York, New York, United States

Local Institution - 120

Charlotte, North Carolina, United States

Local Institution - 112

Portland, Oregon, United States

Local Institution - 118

Philadelphia, Pennsylvania, United States

Local Institution - 103

Nashville, Tennessee, United States

Local Institution - 102

Dallas, Texas, United States

Local Institution - 114

Houston, Texas, United States

Local Institution - 104

Seattle, Washington, United States

Local Institution - 107

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34549906 (View on PubMed)

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm

FDA Safety Alerts and Recalls

https://www.bmsstudyconnect.com/s/US/English/USenHome

BMS Clinical Trial Patient Recruiting

Other Identifiers

U1111-1243-5088

Identifier Type: OTHER

Identifier Source: secondary_id

BB2121-MM-004

Identifier Type: -

Identifier Source: org_study_id