KarMMa: Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Administration of bb2121 bb2121 autologous CAR T cells will be infused at a dose ranging from 15 - 450 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy. |
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).
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Outcome Measures
Primary Outcome Measures
- Overall Response Rate (ORR) [Minimum of 24 months post-bb2121 infusion]
Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma.
Secondary Outcome Measures
- Complete Response (CR) Rate [Minimum of 24 months post-bb2121 infusion]
Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma
- Time to Response [Minimum of 24 months post-bb2121 infusion]
Time from first bb2121 infusion to first documentation of response
- Duration of Response [Minimum of 24 months post-bb2121 infusion]
Time from first response to disease progression or death from any cause
- Progression-free Survival (PFS) [Minimum of 24 months post-bb2121 infusion]
Time from first bb2121 infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first
- Time to Progression (TTP) [Minimum of 24 months post-bb2121 infusion]
Time from first bb2121 infusion to first documentation of PD
- Overall Survival (OS) [Minimum of 24 months post-bb2121 infusion]
Time from first bb2121 infusion to time of death due to any cause
- Adverse Events (AEs) [Minimum of 24 months post-bb2121 infusion]
Number of participants with adverse events (AEs), severity of adverse events, adverse events of special interest (AESI), and serious adverse events (SAEs)
- Pharmacokinetics - Cmax [Minimum of 24 months post-bb2121 infusion]
The maximum transgene level at Tmax
- Pharmacokinetics - Tmax [Minimum of 24 months post-bb2121 infusion]
Time to peak transgene level
- Pharmacokinetics - AUC [Minimum of 24 months post-bb2121 infusion]
Area under the curve of the transgene level
- Immunogenicity [Minimum of 24 months post-bb2121 infusion]
Development of an anti-CAR antibody response
- Minimal Residual Disease (MRD) [Minimum of 24 months post-bb2121 infusion]
Proportion of MRD evaluable subjects that are MRD negative
- Subject-reported outcomes as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30) [Minimum of 24 months post-bb2121 infusion]
Questionnaire will be used as a measure of health-related quality of life
- Subject-reported outcomes as measured by EuroQoL Group EQ-5D-5L Health Questionnaire [: Minimum of 24 months post-bb2121 infusion]
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
- Subject-reported outcomes as measured by EORTC-QLQ-MY20 [Minimum of 24 months post-bb2121 infusion]
Is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality
Eligibility Criteria
Criteria
Inclusion Criteria:
Eligibility is determined prior to leukapheresis. Subjects must satisfy the following criteria to be enrolled in the study:
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Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
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Documented diagnosis of multiple myeloma
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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.
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Must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen.
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Must have received a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.
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Must be refractory to the last treatment regimen.
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Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
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Subjects must have measurable disease, including at least one of the criteria below:
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Serum M-protein greater or equal to 1.0 g/dL
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Urine M-protein greater or equal to 200 mg/24 h
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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
- 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:
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Subjects with known central nervous system involvement with myeloma.
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History or presence of clinically relevant central nervous system (CNS) pathology.
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Subjects with active or history of plasma cell leukemia.
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Subjects with solitary plasmacytomas or non-secretory myeloma without other evidence of measurable disease
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Inadequate organ function
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Ongoing treatment with chronic immunosuppressants
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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
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Evidence of human immunodeficiency virus (HIV) infection.
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Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV)
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Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV) and Hepatitis C virus (HCV)
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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.
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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
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Pregnant or lactating women.
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Subject with known hypersensitivity to any component of bb2121 productThe presence of any of the following will exclude a subject from enrollment:
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Subjects with known central nervous system involvement with myeloma. 2. History or presence of clinically relevant central nervous system (CNS) pathology.
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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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Local Institution - 108 | San Francisco | California | United States | 94143 |
2 | University of California - San Francisco | San Francisco | California | United States | 94143 |
3 | Emory University | Atlanta | Georgia | United States | 30322 |
4 | Local Institution - 103 | Atlanta | Georgia | United States | 30322 |
5 | Local Institution - 107 | Boston | Massachusetts | United States | 02114 |
6 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
7 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02214 |
8 | Local Institution - 106 | Boston | Massachusetts | United States | 02215 |
9 | Local Institution - 105 | Rochester | Minnesota | United States | 55905 |
10 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
11 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
12 | Local Institution - 102 | Hackensack | New Jersey | United States | 07601 |
13 | Local Institution - 109 | New York | New York | United States | 10029 |
14 | Mt. Sinai Medical Center | New York | New York | United States | 10029 |
15 | Local Institution - 101 | Nashville | Tennessee | United States | 37203 |
16 | Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
17 | Local Institution - 104 | Dallas | Texas | United States | 75390 |
18 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
19 | Universitaire Ziekenhuizen Leuven | Leuven | Flemish Brabant | Belgium | 3000 |
20 | Local Institution - 201 | Leuven | Belgium | B-3000 | |
21 | Local Institution - 301 | Toronto | Ontario | Canada | M5G 2M9 |
22 | Princess Margaret Cancer Centre | Toronto | Canada | M5G 2M9 | |
23 | Centre Hospitalier Regional Universitaire de Lille-Hopital Calude Huriez Service des Maladies du Sang | Lille | Hauts-de-France | France | 59037 |
24 | Centre Hospitalier Universitaire de Nantes - Hotel Dieu | Nantes | Pays De La Loire | France | 44093 |
25 | Local Institution - 402 | Lille | France | 59037 | |
26 | Local Institution - 401 | Nantes | France | 44093 | |
27 | Universitatsklinikum Heidelberg Medizinische Klinik Krehl-Klinik Haematologie, Onkologie, Rheumato | Heidelberg | Baden-Württemberg | Germany | 69120 |
28 | University of Tübingen | Tübingen | Baden-Württemberg | Germany | 72076 |
29 | Universitatsklinikum Würzburg | Würzburg | Bavaria | Germany | 97080 |
30 | Local Institution - 502 | Heidelberg | Germany | 69120 | |
31 | Local Institution - 503 | Tübingen | Germany | 72076 | |
32 | Local Institution - 501 | Würzburg | Germany | 97080 | |
33 | Azienda Ospedaliero Universitaria Di Bologna Policlinico | Bologna | Emilia-Romagna | Italy | 40138 |
34 | Local Institution - 602 | Bergamo | Italy | 24128 | |
35 | Ospedali Riuniti di Bergamo | Bergamo | Italy | 24128 | |
36 | Local Institution - 601 | Bologna | Italy | 40138 | |
37 | Tokai University Hospital | Isehara | Kanagawa | Japan | 259-1193 |
38 | Jichi Medical University Hospital | Shimotsuke | Tochigi | Japan | 3290498 |
39 | Japan Red Cross Medical Center | Shibuya-ku | Tokyo | Japan | 150-8935 |
40 | Local Institution - 803 | Isehara City, Kanagawa | Japan | 259-1193 | |
41 | Local Institution - 801 | Shibuya-ku | Japan | 150-8935 | |
42 | Local Institution - 802 | Shimotsuke | Japan | 329-0498 | |
43 | Local Institution - 804 | Shinjuku City | Japan | 162-8666 | |
44 | Tokyo Women's Medical University Hospital | Shinjuku City | Japan | 162-8666 | |
45 | Hospital Universitari Germans Trias i Pujol Can Ruti | Badalona | Barcelona | Spain | 08916 |
46 | Clinica Universidad de Navarra | Pamplona | Navarre | Spain | 31008 |
47 | Local Institution - 702 | Badalona (Barcelona) | Spain | 08916 | |
48 | Local Institution - 701 | Pamplona | Spain | 31008 |
Sponsors and Collaborators
- Celgene
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- BB2121-MM-001
- U1111-1202-5554
- 2017-002245-29