NCT03361748 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2025-05-23

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Response Rate

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outcome · POSTED

Complete Response Rate

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outcome · POSTED

Time to Response

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outcome · POSTED

Duration of Response

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · POSTED

Time to Progression (TTP)

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outcome · POSTED

Overall Survival

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outcome · POSTED

Number of Participants With Safety Related Events

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outcome · POSTED

Cmax

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outcome · POSTED

AUC 0-9M

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outcome · POSTED

Tmax

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outcome · POSTED

Number of Participants With Anti-CAR-Antibodies

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Mean Change From Baseline on the EORTC QLQ-C30 - Pain

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outcome · POSTED

Mean Change From Baseline on the EORTC QLQ-C30 - Physical Functioning

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outcome · POSTED

Mean Change From Baseline on the EORTC QLQ-C30 - Cognitive Functioning

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outcome · POSTED

Mean Change From Baseline on the EORTC QLQ-C30 - Global Heath/QoL

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outcome · POSTED

Mean Change From Baseline on the EORTC QLQ-MY20 - Disease Symptoms

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outcome · POSTED

Mean Change From Baseline on the EORTC QLQ-MY20 - Side Effects

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outcome · POSTED

Mean Change From Baseline on the EQ-5D-5L Index

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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 Names
Biological: bb2121
label
Administration of bb2121
type
EXPERIMENTAL

interventions

arm Group Labels
Administration of bb2121
description
: 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).
name
bb2121
type
BIOLOGICAL

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 149
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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).
measure
Overall Response Rate
time Frame
From first dose to 24 Months

secondary Outcomes

description
Percentage of participants who achieved CR or sCR according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC.
measure
Complete Response Rate
time Frame
From first dose to 24 Months
description
Time from first bb2121 infusion to first documentation of response of PR or better.
measure
Time to Response
time Frame
From first dose to initial response (approximately on average 1.2 months, max of 8.8 months)
description
Time from first documentation of response or PR or better to first documentation of disease progression or death from any cause, whichever occurs first.
measure
Duration of Response
time Frame
From first dose to 24 months after first dose
description
Time from first bb2121 infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first.
measure
Progression Free Survival (PFS)
time Frame
From first dose to 24 months after first dose
description
Time from first bb2121 infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first.
measure
Time to Progression (TTP)
time Frame
From first dose to 24 months after first dose
description
Time from first bb2121 infusion to time of death due to any cause.
measure
Overall Survival
time Frame
From screening to the end of follow up (approximately 5 years and 2 months)
description
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.
measure
Number of Participants With Safety Related Events
time Frame
From screening to the end of follow up (approximately 5 years and 2 months)
description
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.
measure
Cmax
time Frame
From first dose to the end of follow up (Approximately 5 years)
description
The AUC of the transgene level from the time of dosing to 9 months
measure
AUC 0-9M
time Frame
at 9 months post first dose (Approximtately 9 Months)
description
Tmax: The time of maximum observed transgene level, obtained directly from the observed transgene level - time.
measure
Tmax
time Frame
From first dose to the end of follow up (Approximately 5 years)
description
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.
measure
Number of Participants With Anti-CAR-Antibodies
time Frame
From first dose to the end of follow up (Approximately 5 years)
description
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.
measure
Percentage of Participants Who Achieved >= VGPR and MRD Negative Status
time Frame
From screening to the end of follow up (Approximately 5 years and 2 months)

Full 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.
detailed Description: Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured.

Source references

references

citation
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