Clinical trial NCT03361748: Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma
Official title: A Phase 2, Multicenter Study to Determine the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Efficacy and Safety
BB2121
CAR T Cell
BCMA
Relapsed and Refractory
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2017-12-05
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate
timeFrame: From first dose to 24 Months
Secondary outcomes:
measure: Complete Response Rate
timeFrame: From first dose to 24 Months
measure: Time to Response
timeFrame: From first dose to initial response (approximately on average 1.2 months, max of 8.8 months)
measure: Duration of Response
timeFrame: From first dose to 24 months after first dose
measure: Progression Free Survival (PFS)
timeFrame: From first dose to 24 months after first dose
measure: Time to Progression (TTP)
timeFrame: From first dose to 24 months after first dose
measure: Overall Survival
timeFrame: From screening to the end of follow up (approximately 5 years and 2 months)
measure: Number of Participants With Safety Related Events
timeFrame: From screening to the end of follow up (approximately 5 years and 2 months)
measure: Cmax
timeFrame: From first dose to the end of follow up (Approximately 5 years)
measure: AUC 0-9M
timeFrame: at 9 months post first dose (Approximtately 9 Months)
measure: Tmax
timeFrame: From first dose to the end of follow up (Approximately 5 years)
measure: Number of Participants With Anti-CAR-Antibodies
timeFrame: From first dose to the end of follow up (Approximately 5 years)
measure: Percentage of Participants Who Achieved >= VGPR and MRD Negative Status
timeFrame: From screening to the end of follow up (Approximately 5 years and 2 months)
measure: Mean Change From Baseline on the EORTC QLQ-C30 - Fatigue.
timeFrame: At Day 1 and at specific time points up to month 24
measure: Mean Change From Baseline on the EORTC QLQ-C30 - Pain
timeFrame: At Day 1 and at specific time points up to month 24
measure: Mean Change From Baseline on the EORTC QLQ-C30 - Physical Functioning
timeFrame: At Day 1 and at specific time points up to month 24
measure: Mean Change From Baseline on the EORTC QLQ-C30 - Cognitive Functioning
timeFrame: At Day 1 and at specific time points up to month 24
measure: Mean Change From Baseline on the EORTC QLQ-C30 - Global Heath/QoL
timeFrame: At Day 1 and at specific time points up to month 24
measure: Mean Change From Baseline on the EORTC QLQ-MY20 - Disease Symptoms
timeFrame: At Day 1 and at specific time points up to month 24
measure: Mean Change From Baseline on the EORTC QLQ-MY20 - Side Effects
timeFrame: At Day 1 and at specific time points up to month 24
measure: Mean Change From Baseline on the EQ-5D-5L Index
timeFrame: At Day 1 and at specific time points up to month 24
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Local Institution - 108
state: California
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Local Institution - 103
state: Georgia
city: Boston
country: United States
facility: Local Institution - 107
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 106
state: Massachusetts
city: Rochester
country: United States
facility: Local Institution - 105
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: Local Institution - 102
state: New Jersey
city: New York
country: United States
facility: Local Institution - 109
state: New York
city: New York
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: Nashville
country: United States
facility: Local Institution - 101
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Local Institution - 104
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
state: Flemish Brabant
city: Leuven
country: Belgium
facility: Local Institution - 201
city: Toronto
country: Canada
facility: Local Institution - 301
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire de Lille-Hopital Calude Huriez Service des Maladies du Sang
state: Hauts-de-France
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes - Hotel Dieu
state: Pays De La Loire
city: Lille
country: France
facility: Local Institution - 402
city: Nantes
country: France
facility: Local Institution - 401
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg Medizinische Klinik Krehl-Klinik Haematologie, Onkologie, Rheumato
state: Baden-Württemberg
city: Tübingen
country: Germany
facility: University of Tübingen
state: Baden-Württemberg
city: Würzburg
country: Germany
facility: Universitatsklinikum Würzburg
state: Bavaria
city: Heidelberg
country: Germany
facility: Local Institution - 502
city: Tübingen
country: Germany
facility: Local Institution - 503
city: Würzburg
country: Germany
facility: Local Institution - 501
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna Policlinico
state: Emilia-Romagna
city: Bergamo
country: Italy
facility: Local Institution - 602
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
city: Bologna
country: Italy
facility: Local Institution - 601
city: Isehara
country: Japan
facility: Tokai University Hospital
state: Kanagawa
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Shibuya-ku
country: Japan
facility: Japan Red Cross Medical Center
state: Tokyo
city: Isehara City, Kanagawa
country: Japan
facility: Local Institution - 803
city: Shibuya-ku
country: Japan
facility: Local Institution - 801
city: Shimotsuke
country: Japan
facility: Local Institution - 802
city: Shinjuku City
country: Japan
facility: Local Institution - 804
city: Shinjuku City
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol Can Ruti
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarre
city: Badalona (Barcelona)
country: Spain
facility: Local Institution - 702
city: Pamplona
country: Spain
facility: Local Institution - 701
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
affiliation: Celgene
name: Kristen Hege
role: STUDY_DIRECTOR
References:
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.
citation: 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.
citation: Shah N, Mojebi A, Ayers D, Cope S, Dhanasiri S, Davies FE, Hari P, Patel P, Hege K, Dhanda D. Indirect treatment comparison of idecabtagene vicleucel versus conventional care in triple-class exposed multiple myeloma. J Comp Eff Res. 2022 Jul;11(10):737-749. doi: 10.2217/cer-2022-0045. Epub 2022 Apr 29.
citation: Sharma P, Kanapuru B, George B, Lin X, Xu Z, Bryan WW, Pazdur R, Theoret MR. FDA Approval Summary: Idecabtagene Vicleucel for Relapsed or Refractory Multiple Myeloma. Clin Cancer Res. 2022 May 2;28(9):1759-1764. doi: 10.1158/1078-0432.CCR-21-3803.
citation: Delforge M, Shah N, Miguel JSF, Braverman J, Dhanda DS, Shi L, Guo S, Yu P, Liao W, Campbell TB, Munshi NC. Health-related quality of life with idecabtagene vicleucel in relapsed and refractory multiple myeloma. Blood Adv. 2022 Feb 22;6(4):1309-1318. doi: 10.1182/bloodadvances.2021005913.
citation: Da Via MC, Dietrich O, Truger M, Arampatzi P, Duell J, Heidemeier A, Zhou X, Danhof S, Kraus S, Chatterjee M, Meggendorfer M, Twardziok S, Goebeler ME, Topp MS, Hudecek M, Prommersberger S, Hege K, Kaiser S, Fuhr V, Weinhold N, Rosenwald A, Erhard F, Haferlach C, Einsele H, Kortum KM, Saliba AE, Rasche L. Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma. Nat Med. 2021 Apr;27(4):616-619. doi: 10.1038/s41591-021-01245-5. Epub 2021 Feb 22.