NCT03361748CompletedPhase 2
A Phase 2, Multicenter Study to Determine the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Celgene
- Enrollment
- 149
- Locations
- 48
- Primary Endpoint
- Overall Response Rate
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- 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:
- •Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
- •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.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •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
- •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:
- •Subjects with known central nervous system involvement with myeloma.
- •History or presence of clinically relevant central nervous system (CNS) pathology.
- •Subjects with active or history of plasma cell leukemia.
- •Subjects with solitary plasmacytomas or non-secretory myeloma without other evidence of measurable disease
- •Inadequate organ function
- •Ongoing treatment with chronic immunosuppressants
- •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
- •Evidence of human immunodeficiency virus (HIV) infection.
- •Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV)
- •Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV) and Hepatitis C virus (HCV)
- •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.
- •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
- •Pregnant or lactating women.
- •Subject with known hypersensitivity to any component of bb2121 productThe presence of any of the following will exclude a subject from enrollment:
- •Subjects with known central nervous system involvement with myeloma.
- •History or presence of clinically relevant central nervous system (CNS) pathology.
- •Subjects with active or history of plasma cell leukemia.
- •Subjects with solitary plasmacytomas or non-secretory myeloma without other evidence of measurable disease
- •Inadequate organ function
- •Ongoing treatment with chronic immunosuppressants
- •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
- •Evidence of human immunodeficiency virus (HIV) infection.
- •Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV) and Hepatitis C virus (HCV)
- •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.
- •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
- •Pregnant or lactating women. 13 Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, or tocilizumab.
Arms & Interventions
Administration of bb2121
Experimental
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.
Intervention: bb2121 (Biological)
Outcomes
Primary Outcomes
Overall Response Rate
Time Frame: From first dose to 24 Months
Number of participants who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an independent response committee (IRC).
Secondary Outcomes
- Number of Participants With Safety Related Events(From screening to the end of follow up (approximately 5 years and 2 months))
- Complete Response Rate(From first dose to 24 Months)
- Cmax(From first dose to the end of follow up (Approximately 5 years))
- Time to Response(From first dose to initial response (approximately on average 1.2 months, max of 8.8 months))
- Duration of Response(From first dose to 24 months after first dose)
- Progression Free Survival (PFS)(From first dose to 24 months after first dose)
- Time to Progression (TTP)(From first dose to 24 months after first dose)
- AUC 0-9M(at 9 months post first dose (Approximtately 9 Months))
- Tmax(From first dose to the end of follow up (Approximately 5 years))
- Number of Participants With Anti-CAR-Antibodies(From first dose to the end of follow up (Approximately 5 years))
- Overall Survival(From screening to the end of follow up (approximately 5 years and 2 months))
- Percentage of Participants Who Achieved >= VGPR and MRD Negative Status(From screening to the end of follow up (Approximately 5 years and 2 months))
- Mean Change From Baseline on the EORTC QLQ-C30 - Fatigue.(At Day 1 and at specific time points up to month 24)
- Mean Change From Baseline on the EORTC QLQ-C30 - Pain(At Day 1 and at specific time points up to month 24)
- Mean Change From Baseline on the EORTC QLQ-C30 - Physical Functioning(At Day 1 and at specific time points up to month 24)
- Mean Change From Baseline on the EORTC QLQ-C30 - Cognitive Functioning(At Day 1 and at specific time points up to month 24)
- Mean Change From Baseline on the EORTC QLQ-C30 - Global Heath/QoL(At Day 1 and at specific time points up to month 24)
- Mean Change From Baseline on the EORTC QLQ-MY20 - Disease Symptoms(At Day 1 and at specific time points up to month 24)
- Mean Change From Baseline on the EORTC QLQ-MY20 - Side Effects(At Day 1 and at specific time points up to month 24)
- Mean Change From Baseline on the EQ-5D-5L Index(At Day 1 and at specific time points up to month 24)
Investigators
Study Sites (48)
Loading locations...
Similar Trials
Completed
Phase 2
PM8002 in Combination With Chemotherapy as First Line Therapy in Hepatocellular CarcinomaHepatocellular CarcinomaNCT05864105Biotheus Inc.35
Withdrawn
Phase 2
A Study of Mitoxantrone Hydrochloride Liposome Injection for Relapsing Multiple SclerosisRelapsing Multiple SclerosisNCT05496894CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
Completed
Phase 2
Efficacy and Safety of DaxibotulinumtoxinA (DAXI) for Injection for Treatment of Upper Facial LinesUpper Facial Lines (Glabellar Lines, Forehead Lines, & Lateral Canthal Lines)NCT04259086Revance Therapeutics, Inc.48
Completed
Phase 2
Study of BEBT-908 in the Relapsed or Refractory Diffuse Large B-cell Lymphoma SubjectsRelapsed or Refractory Diffuse Large B-cell LymphomaNCT06074107BeBetter Med Inc128
Active, not recruiting
Phase 2
A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating MutationsAdvanced Solid Tumors With HER2 Mutation,eg:Colorectal,Urothelial,Gastric, Hepatobiliary,Endometrial,Melanoma,Ovarian,Cervical,Salivary Gland,Pancreatic,BreastNCT04639219AstraZeneca102