Safety and Efficacy of bb2121 (Ide-cel) Combinations in Multiple Myeloma

Multiple Myeloma Clinical Trial

— KarMMa-7  

Official title:

An Exploratory Phase 1/2 Trial to Determine Recommended Phase 2 Dose (RP2D), Safety and Preliminary Efficacy of bb2121 (Ide-cel) Combinations in Subjects With Relapsed/Refractory Multiple Myeloma (KarMMa-7)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04855136
• Other study ID #: BB2121-MM-007
• Secondary ID: 2020-003248-10
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 1, 2021
• Est. completion date: December 6, 2026

Study information

• Verified date: November 2023
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a global, open-label, multi-arm, multi-cohort, multi-center, phase 1/2 study to determine the safety, tolerability, efficacy, PK of bb2121 in combination with other therapies in adult subjects with R/RMM.

The following combinations will be

• Arm A will test bb2121 in combination with CC-220 (± low-dose dexamethasone)

• Arm B will test bb2121 in combination with BMS-986405 (JSMD194)

Combination agents being tested may be administered before, concurrently with and/or following (ie, maintenance) bb2121 infusion.

The study will consist of 2 parts: dose finding (Phase 1) and dose expansion (Phase 2). Dose expansion may occur in one or more arms.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 312
• Est. completion date: December 6, 2026
• Est. primary completion date: December 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Participants must satisfy the following criteria to be enrolled in the study:

• Participant has documented diagnosis of MM and measurable disease, defined as:

1. M-protein (serum protein electrophoresis [sPEP = 0.5 g/dL] or urine protein electrophoresis [uPEP]): uPEP = 200 mg/24 hours and/or

2. Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain = 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio

• Participant has received:

1. at least 3 prior MM regimens for Arm A Cohort 1 and Arm B

2. at least 1 but no greater than 3 prior MM regimens for Arm A Cohort 2

• Arm A Cohort 1 and Arm B: Participant has received prior treatment with an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody-containing regimen for at least 2 consecutive cycles.

• Arm A Cohort 2: Participant has received prior treatment with an immunomodulatory agent for at least 2 consecutive cycles.

• Evidence of PD during or within 6 months (measured from the last dose of any drug within the regimen) of completing treatment with the last antimyeloma regimen before study entry.

• Participant achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen.

• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

The presence of any of the following will exclude a participant from enrollment:

• Participant has non-secretory MM or has history of or active plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.

• Participant has any of the following laboratory abnormalities:

1. ANC and Platelets count as reported below

2. Hemoglobin < 8 g/dL (< 4.9 mmol/L) (transfusion is not permitted within 21 days of screening)

3. Creatinine clearance (CrCl) as reported below

4. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)

5. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 ×upper limit of normal (ULN)

6. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for participants with documented Gilbert's syndrome

7. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) 1.5 × ULN, or history of Grade = 2 hemorrhage within 30 days, or participant requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors)

• Participant has inadequate pulmonary function defined as oxygen saturation (SaO2) < 92% on room air.

• Participant has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal.

• Prior exposure to CC-220 (± low-dose dexamethasone) as part of their most recent antimyeloma treatment regimen (Arm A).

• Prior exposure to BMS-986405 (JSMD194) (Arm B).

• Previous history of an allogeneic hematopoietic stem cell transplantation, treatment with any gene therapy-based therapeutic for cancer, investigational cellular therapy for cancer or BCMA targeted therapy.

• Treatment Arm A Cohort 1 and Arm B: participant has received autologous stem cell transplantation (ASCT) within 12 weeks prior to leukapheresis.

• Treatment Arm A Cohort 2: participant has received autologous stem cell transplantation (ASCT) within 12 months prior to leukapheresis.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• BB2121
CAR T Cell Therapy

Drug:
• CC-220
Cereblon (CRBN) E3 ligase modulatory compound (CELMoD)
• BMS-986405
gamma secretase inhibitor (GSI)

Locations

Country	Name	City	State
Spain	Local Institution - 201	Pamplona
Spain	Local Institution - 202	Salamanca
United States	Local Institution - 104	Atlanta	Georgia
United States	Local Institution - 120	Atlanta	Georgia
United States	Local Institution - 117	Birmingham	Alabama
United States	Local Institution - 108	Boston	Massachusetts
United States	Local Institution - 124	Boston	Massachusetts
United States	Local Institution - 111	Charlotte	North Carolina
United States	Local Institution - 114	Chicago	Illinois
United States	Local Institution - 109	Hackensack	New Jersey
United States	Local Institution - 107	Houston	Texas
United States	Local Institution - 101	Jacksonville	Florida
United States	Local Institution - 103	Nashville	Tennessee
United States	Local Institution - 110	New York	New York
United States	New York University Langone	New York	New York
United States	Local Institution - 118	Philadelphia	Pennsylvania
United States	Local Institution - 113	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Does Limiting Toxicity (DLT) rates _Phase 1	Percentage of participants experiencing DLTs	Up to 28 days from start of the combination therapy
Primary	Complete Response Rate (CRR)_ Phase 2	Proportion of participants who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by investigator's review	Up to 24 months
Secondary	Incidence of Adverse Event (AEs)	An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.	Up to 24 months after the last participant received any study treatment
Secondary	Overall Response Rate (ORR)	Proportion of participants who achieved PR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed investigator's review	Up to 24 months after the last participant received any study treatment in the respective cohort
Secondary	Progression-free Survival (PFS)	Time from first study treatment (whichever is given earlier) start date to the date of either first observation of progressive disease or death due to any cause	Up to 24 months after the last participant received any study treatment in the respective cohort
Secondary	Overall Survival (OS)	Time from first study treatment (whichever is given earlier) start date to death due to any cause	Up to 24 months after the last participant received any study treatment in the respective cohort
Secondary	Time to response (TTR)	Time from first study treatment start date to the first date of documented response (PR or better)	Up to 24 months after the last participant received any study treatment in the respective cohort
Secondary	Duration of Response (DoR)	Time from first documentation of response (PR or better) to first documentation of PD or death due to any cause	Up to 24 months after the last participant received any study treatment in the respective cohort
Secondary	Time to next antimyeloma treatment (TTNT)	Time from first study treatment (whichever is given earlier) start date to first day when participant receives another antimyeloma treatment	Up to 24 months after the last participant received any study treatment in the respective cohort
Secondary	Progression-free survival after next antimyeloma therapy (PFS2)	Time from first study treatment (whichever is given earlier) start date to documentation of PD on the next-line treatment or death from any cause, whichever is first.	Up to 24 months after the last participant received any study treatment in the respective cohort
Secondary	Feasibility of maintenance therapy in combination with bb2121	Cumulative incidence of the maintenance therapy starting from bb2121 infusion with death as the competing risk	Up to 4 months after bb2121 infusion in the respective cohort
Secondary	Pharmacokinetics - Cmax_Phase 1 and 2	Maximum transgene level	Up to 24 months after the last participant received any study treatment in the respective cohort
Secondary	Pharmacokinetics - Tmax_Phase 1 and 2	Time to maximum observed transgene level	Up to 24 months after the last participant received any study treatment in the respective cohort
Secondary	Pharmacokinetics - AUC_Phase 1 and 2	Area under the curve of transgene level	Up to 24 months after the last participant received any study treatment in the respective cohort
Secondary	Pharmacokinetics - AUC0-28days _Phase 1 and 2	Area under the curve of transgene level from time 0 to 28 days	Up to 24 months after the last participant received any study treatment in the respective cohort
Secondary	Pharmacokinetics - Tlast _Phase 1 and 2	Time of last measurable transgene level	Up to 24 months after the last participant received any study treatment in the respective cohort

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls