Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

— KarMMa  

Official title:

A Phase 2, Multicenter Study to Determine the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03361748
• Other study ID #: BB2121-MM-001
• Secondary ID: U1111-1202-55542
• Status: Completed
• Phase: Phase 2
• Start date: December 18, 2017
• Est. completion date: December 20, 2023

Study information

• Verified date: January 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open label, single-arm, multicenter, Phase 2 study to evaluate the efficacy and safety of bb2121 in subjects with relapsed and refractory multiple myeloma. A leukapheresis procedure will be performed to manufacture bb2121 chimeric antigen receptor (CAR) modified T cells. Prior to bb2121 infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide.

Description:

Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 149
• Est. completion date: December 20, 2023
• Est. primary completion date: December 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Eligibility is determined prior to leukapheresis. Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject is = 18 years of age at the time of signing the informed consent form (ICF).

2. Documented diagnosis of multiple myeloma

• Must have received at least 3 prior MM treatment regimens. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen.

• Must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen.

• Must have received a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.

• Must be refractory to the last treatment regimen.

3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

4. Subjects must have measurable disease, including at least one of the criteria below:

• Serum M-protein greater or equal to 1.0 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

5. Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subjects with known central nervous system involvement with myeloma.

2. History or presence of clinically relevant central nervous system (CNS) pathology.

3. Subjects with active or history of plasma cell leukemia.

4. Subjects with solitary plasmacytomas or non-secretory myeloma without other evidence of measurable disease

5. Inadequate organ function

6. Ongoing treatment with chronic immunosuppressants

7. Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy

8. Evidence of human immunodeficiency virus (HIV) infection.

9. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV)

10. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV) and Hepatitis C virus (HCV)

11. Subjects with a history of class III or IV congestive heart failure (CHF) or severe non-ischemic cardiomyopathy, history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months.

12. 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

13. Pregnant or lactating women.

14. Subject with known hypersensitivity to any component of bb2121 productThe presence of any of the following will exclude a subject from enrollment:

1. Subjects with known central nervous system involvement with myeloma. 2. History or presence of clinically relevant central nervous system (CNS) pathology.

3. Subjects with active or history of plasma cell leukemia. 4. Subjects with solitary plasmacytomas or non-secretory myeloma without other evidence of measurable disease 5. Inadequate organ function 6. Ongoing treatment with chronic immunosuppressants 7. Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy 8. Evidence of human immunodeficiency virus (HIV) infection. 9. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV) and Hepatitis C virus (HCV) 10. Subjects with a history of class III or IV congestive heart failure (CHF) or severe non-ischemic cardiomyopathy, history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months. 11. 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 12. Pregnant or lactating women. 13 Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, or tocilizumab.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• bb2121
: bb2121 consists of autologous T lymphocytes transduced with an anti-BCMA02 CAR lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR).

Locations

Country	Name	City	State
Belgium	Local Institution - 201	Leuven
Canada	Local Institution - 301	Toronto	Ontario
France	Local Institution - 402	Lille
France	Local Institution - 401	Nantes
Germany	Local Institution - 502	Heidelberg
Germany	Local Institution - 503	Tübingen
Germany	Local Institution - 501	Würzburg
Italy	Local Institution - 602	Bergamo
Italy	Local Institution - 601	Bologna
Japan	Local Institution - 803	Isehara City, Kanagawa
Japan	Local Institution - 801	Shibuya-ku
Japan	Local Institution - 802	Shimotsuke
Japan	Local Institution - 804	Shinjuku City
Spain	Local Institution - 702	Badalona (Barcelona)
Spain	Local Institution - 701	Pamplona
United States	Local Institution - 103	Atlanta	Georgia
United States	Local Institution - 106	Boston	Massachusetts
United States	Local Institution - 107	Boston	Massachusetts
United States	Local Institution - 104	Dallas	Texas
United States	Local Institution - 102	Hackensack	New Jersey
United States	Local Institution - 101	Nashville	Tennessee
United States	Local Institution - 109	New York	New York
United States	Local Institution - 105	Rochester	Minnesota
United States	Local Institution - 108	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Japan,  Spain, 

References & Publications (2)

Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, Raje N, Lin Y, Siegel D, Oriol A, Moreau P, Yakoub-Agha I, Delforge M, Cavo M, Einsele H, Goldschmidt H, Weisel K, Rambaldi A, Reece D, Petrocca F, Massaro M, Connarn JN, Kaiser S, Patel P, Huang L, Campbell TB, Hege K, San-Miguel J. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021 Feb 25;384(8):705-716. doi: 10.1056/NEJMoa2024850. — View Citation

Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, Liedtke M, Rosenblatt J, Maus MV, Turka A, Lam LP, Morgan RA, Friedman K, Massaro M, Wang J, Russotti G, Yang Z, Campbell T, Hege K, Petrocca F, Quigley MT, Munshi N, Kochenderfer JN. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2019 May 2;380(18):1726-1737. doi: 10.1056/NEJMoa1817226. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma.	Minimum of 24 months post-bb2121 infusion
Secondary	Complete Response (CR) Rate	Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma	Minimum of 24 months post-bb2121 infusion
Secondary	Time to Response	Time from first bb2121 infusion to first documentation of response	Minimum of 24 months post-bb2121 infusion
Secondary	Duration of Response	Time from first response to disease progression or death from any cause	Minimum of 24 months post-bb2121 infusion
Secondary	Progression-free Survival (PFS)	Time from first bb2121 infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first	Minimum of 24 months post-bb2121 infusion
Secondary	Time to Progression (TTP)	Time from first bb2121 infusion to first documentation of PD	Minimum of 24 months post-bb2121 infusion
Secondary	Overall Survival (OS)	Time from first bb2121 infusion to time of death due to any cause	Minimum of 24 months post-bb2121 infusion
Secondary	Adverse Events (AEs)	Number of participants with adverse events (AEs), severity of adverse events, adverse events of special interest (AESI), and serious adverse events (SAEs)	Minimum of 24 months post-bb2121 infusion
Secondary	Pharmacokinetics - Cmax	The maximum transgene level at Tmax	Minimum of 24 months post-bb2121 infusion
Secondary	Pharmacokinetics - Tmax	Time to peak transgene level	Minimum of 24 months post-bb2121 infusion
Secondary	Pharmacokinetics - AUC	Area under the curve of the transgene level	Minimum of 24 months post-bb2121 infusion
Secondary	Immunogenicity	Development of an anti-CAR antibody response	Minimum of 24 months post-bb2121 infusion
Secondary	Minimal Residual Disease (MRD)	Proportion of MRD evaluable subjects that are MRD negative	Minimum of 24 months post-bb2121 infusion
Secondary	Subject-reported outcomes as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30)	Questionnaire will be used as a measure of health-related quality of life	Minimum of 24 months post-bb2121 infusion
Secondary	Subject-reported outcomes as measured by EuroQoL Group EQ-5D-5L Health Questionnaire	Is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal	: Minimum of 24 months post-bb2121 infusion
Secondary	Subject-reported outcomes as measured by EORTC-QLQ-MY20	Is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality	Minimum of 24 months post-bb2121 infusion

External Links

•   BMS Clinical Trial Information