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

Celgene149 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

149

Conditions

Multiple Myeloma

Interventions

bb2121BIOLOGICAL

: 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).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (48)

Outcomes

Primary Outcomes

Overall Response Rate

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).

Time frame: From first dose to 24 Months

Secondary Outcomes

Complete Response Rate

Percentage of participants who achieved CR or sCR according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC.

Time frame: From first dose to 24 Months

Time to Response

Time from first bb2121 infusion to first documentation of response of PR or better.

Time frame: From first dose to initial response (approximately on average 1.2 months, max of 8.8 months)

Duration of Response

Time from first documentation of response or PR or better to first documentation of disease progression or death from any cause, whichever occurs first.

Time frame: From first dose to 24 months after first dose

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.

Time frame: From first dose to 24 months after first dose

Time to Progression (TTP)

Time from first bb2121 infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first.

Time frame: From first dose to 24 months after first dose

Overall Survival

Data from ClinicalTrials.gov

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Local Institution - 108

San Francisco, California, United States

University of California - San Francisco

San Francisco, California, United States

Emory University

Atlanta, Georgia, United States

Local Institution - 103

Atlanta, Georgia, United States

Local Institution - 107

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Local Institution - 106

Boston, Massachusetts, United States

Local Institution - 105

Rochester, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

...and 38 more locations

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

Time frame: From screening to the end of follow up (approximately 5 years and 2 months)

Number of Participants With Safety Related Events

Number of participants with adverse events (AEs), adverse events of special interest (AESI), serious adverse events (SAEs), cytokine release syndrome, neurotoxicity, infection and clinically signifcant laboratory abnormalities.

Time frame: From screening to the end of follow up (approximately 5 years and 2 months)

Cmax

Cmax is defined as the maximum transgene level at Tmax Tmax: The time of maximum observed transgene level, obtained directly from the observed transgene level - time.

Time frame: From first dose to the end of follow up (Approximately 5 years)

AUC 0-9M

The AUC of the transgene level from the time of dosing to 9 months

Time frame: at 9 months post first dose (Approximtately 9 Months)

Tmax

Tmax: The time of maximum observed transgene level, obtained directly from the observed transgene level - time.

Time frame: From first dose to the end of follow up (Approximately 5 years)

Number of Participants With Anti-CAR-Antibodies

Number of Participants with Anti-CAR-Antibodies. Pre-postive is defined by last value before or on bb2121 infusion date is positive Post-positve is defined by at least one positive value post bb2121 infusion.

Time frame: From first dose to the end of follow up (Approximately 5 years)

Percentage of Participants Who Achieved >= VGPR and MRD Negative Status

Percentage of participants who achieved ≥ VGPR and MRD negative status at a sensitivity of 10-⁵ at any time point within 3 months prior to achieving at least VGPR until the time of PD/death. MRD in the bone marrow will be measured using both next generation sequencing (NGS) techniques measuring immunoglobulin gene rearrangements of the malignant clone. MRD will be reported with a sensitivity of 10-⁴, 10-⁵, and 10-⁶ nucleated cells. The primary analysis for MRD negative response will use the sensitivity of 10-⁵. MRD = Minimal Residual Disease PD = Progressive Disease VGPR = Very good partial response.

Time frame: From screening to the end of follow up (Approximately 5 years and 2 months)

Mean Change From Baseline on the EORTC QLQ-C30 - Fatigue.

Mean change from baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) The QLQ-C30 employs a week recall period for all items. All items will be scored from 0 to 100. The average of the scores will represent the symptoms score. A high score for a symptom scale/item represents a high level of symptomatic problem.