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

Sponsor
Celgene (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03361748
Collaborator
(none)
149
48
1
83.5
3.1
0

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
  • Biological: bb2121
Phase 2

Detailed Description

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

Study Design

Study Type:
Interventional
Actual Enrollment :
149 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multicenter Study to Determine the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma
Actual Study Start Date :
Dec 13, 2017
Anticipated Primary Completion Date :
Nov 28, 2024
Anticipated Study Completion Date :
Nov 28, 2024

Arms and Interventions

Arm Intervention/Treatment
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).

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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

  2. Time to Response [Minimum of 24 months post-bb2121 infusion]

    Time from first bb2121 infusion to first documentation of response

  3. Duration of Response [Minimum of 24 months post-bb2121 infusion]

    Time from first response to disease progression or death from any cause

  4. 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

  5. Time to Progression (TTP) [Minimum of 24 months post-bb2121 infusion]

    Time from first bb2121 infusion to first documentation of PD

  6. Overall Survival (OS) [Minimum of 24 months post-bb2121 infusion]

    Time from first bb2121 infusion to time of death due to any cause

  7. 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)

  8. Pharmacokinetics - Cmax [Minimum of 24 months post-bb2121 infusion]

    The maximum transgene level at Tmax

  9. Pharmacokinetics - Tmax [Minimum of 24 months post-bb2121 infusion]

    Time to peak transgene level

  10. Pharmacokinetics - AUC [Minimum of 24 months post-bb2121 infusion]

    Area under the curve of the transgene level

  11. Immunogenicity [Minimum of 24 months post-bb2121 infusion]

    Development of an anti-CAR antibody response

  12. Minimal Residual Disease (MRD) [Minimum of 24 months post-bb2121 infusion]

    Proportion of MRD evaluable subjects that are MRD negative

  13. 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

  14. 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

  15. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

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

  2. 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

  1. 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:

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

  16. 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
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

Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT03361748
Other Study ID Numbers:
  • BB2121-MM-001
  • U1111-1202-5554
  • 2017-002245-29
First Posted:
Dec 5, 2017
Last Update Posted:
Jul 20, 2022
Last Verified:
Jul 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Celgene
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 20, 2022