Clinical trial NCT04855136: Safety and Efficacy of bb2121 (Ide-cel) Combinations in Multiple Myeloma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Relapsed/Refractory Multiple Myeloma
BB2121
ide-cel
CC-220
JSMD194
BMS-986405
DPd
PVd
CAR T
KarMMa-7
Phase I
Phase II
DARA
POM
BTZ
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2021-04-22
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Does Limiting Toxicity (DLT) rates _Phase 1
timeFrame: Up to 28 days from start of the combination therapy
measure: Complete Response Rate (CRR)_ Phase 2
timeFrame: Up to 24 months
Secondary outcomes:
measure: Incidence of Adverse Event (AEs)
timeFrame: Up to 24 months after the last participant received any study treatment
measure: Overall Response Rate (ORR)
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
measure: Progression-free Survival (PFS)
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
measure: Overall Survival (OS)
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
measure: Time to response (TTR)
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
measure: Duration of Response (DoR)
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
measure: Time to next antimyeloma treatment (TTNT)
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
measure: Progression-free survival after next antimyeloma therapy (PFS2)
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
measure: Feasibility of maintenance therapy in combination with bb2121
timeFrame: Up to 4 months after bb2121 infusion in the respective cohort
measure: Pharmacokinetics - Cmax_Phase 1 and 2
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
measure: Pharmacokinetics - Tmax_Phase 1 and 2
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
measure: Pharmacokinetics - AUC_Phase 1 and 2
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
measure: Pharmacokinetics - AUC0-28days _Phase 1 and 2
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
measure: Pharmacokinetics - Tlast _Phase 1 and 2
timeFrame: Up to 24 months after the last participant received any study treatment in the respective cohort
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 117
state: Alabama
city: San Francisco
country: United States
facility: Local Institution - 113
state: California
city: Jacksonville
country: United States
facility: Local Institution - 101
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 104
state: Georgia
city: Atlanta
country: United States
facility: Local Institution - 120
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 114
state: Illinois
city: Boston
country: United States
facility: Local Institution - 108
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 124
state: Massachusetts
city: Hackensack
country: United States
facility: Local Institution - 109
state: New Jersey
city: New York
country: United States
facility: New York University Langone
state: New York
city: New York
country: United States
facility: Local Institution - 110
state: New York
city: Charlotte
country: United States
facility: Local Institution - 111
state: North Carolina
city: Philadelphia
country: United States
facility: Local Institution - 118
state: Pennsylvania
city: Nashville
country: United States
facility: Local Institution - 103
state: Tennessee
city: Houston
country: United States
facility: Local Institution - 107
state: Texas
city: Pamplona
country: Spain
facility: Local Institution - 201
city: Salamanca
country: Spain
facility: Local Institution - 202
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: