Clinical Trials /

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

NCT04855136

Description:

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) - Arm C will test bb2121 in combination with one of the following standard triplet regimens: 1) Daratumumab (DARA) in combination with pomalidomide (POM) and low-dose dexamethasone (DPd); 2) Pomalidomide (POM) in combination with bortezomib (BTZ) and low-dose dexamethasone (PVd) 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.

Related Conditions:
  • Multiple Myeloma
  • Non-Secretory Plasma Cell Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: BB2121-MM-007
  • SECONDARY ID: 2020-003248-10
  • NCT ID: NCT04855136

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
BB2121ide-celArm A- bb2121 in combination with CC-220 (± low-dose dexamethasone)
CC-220Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone)
BMS-986405JSMD194Arm B- bb2121 in combination with BMS-986405 (JSMD194)
PomalidomideArm C-bb2121 in combination with Daratumumab+pomalidomide+low-dose dexamethasone or POM +bortezomib
DexamethasoneArm C-bb2121 in combination with Daratumumab+pomalidomide+low-dose dexamethasone or POM +bortezomib
BortezomibArm C-bb2121 in combination with Daratumumab+pomalidomide+low-dose dexamethasone or POM +bortezomib

Purpose

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) - Arm C will test bb2121 in combination with one of the following standard triplet regimens: 1) Daratumumab (DARA) in combination with pomalidomide (POM) and low-dose dexamethasone (DPd); 2) Pomalidomide (POM) in combination with bortezomib (BTZ) and low-dose dexamethasone (PVd) 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.

Trial Arms

NameTypeDescriptionInterventions
Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone)Experimentalbb2121 will be administered at a target dose of 450 x 10^6 CAR+T cells. The combination agent will be administered at different doses and/ or schedules, depending on dose limiting toxicity (DLT) evaluation.
  • BB2121
  • CC-220
Arm B- bb2121 in combination with BMS-986405 (JSMD194)Experimentalbb2121 will be administered at a target dose of 450 x 10^6 CAR+T cells. The combination agent will be administered during Month 1 starting from the day of bb2121 infusion.
  • BB2121
  • BMS-986405
Arm C-bb2121 in combination with Daratumumab+pomalidomide+low-dose dexamethasone or POM +bortezomibExperimentalbb2121 will be administered at a target dose of 450 x 10^6 CAR+T cells. The combination agents will be administered as follow: Cohort 1 (DPd) DARA, POM and dexamethasone at M3D1 until disease progression. Cohort 2 (PVd) POM, BTZ and dexamethasone at M3D1 until disease progression
  • BB2121
  • Pomalidomide
  • Dexamethasone
  • Bortezomib

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] or urine protein electrophoresis
                  [uPEP]): sPEP ≥ 0.5 g/dL or 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 and Arm C.

          -  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 and Arm C: 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).

          -  Prior exposure to DARA in combination with POM with or without dexamethasone (DP±d) as
             part of their most recent antimyeloma treatment regimen (Arm C Cohort 1).

          -  Prior exposure to POM in combination with BTZ with or without dexamethasone (PV± d as
             part of their most recent antimyeloma treatment regimen (Arm C Cohort 2).

          -  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 Arms A Cohort 2 and Arm C: participant has received autologous stem cell
             transplantation (ASCT) within 12 months prior to leukapheresis.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Does Limiting Toxicity (DLT) rates _Phase 1
Time Frame:Up to 28 days from start of the combination therapy
Safety Issue:
Description:Percentage of participants experiencing DLTs

Secondary Outcome Measures

Measure:Incidence of Adverse Event (AEs)
Time Frame:Up to 24 months after the last participant received any study treatment
Safety Issue:
Description: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.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description:Proportion of participants who achieved PR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed investigator's review
Measure:Progression-free Survival (PFS)
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description: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
Measure:Overall Survival (OS)
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description:Time from first study treatment (whichever is given earlier) start date to death due to any cause
Measure:Time to response (TTR)
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description:Time from first study treatment start date to the first date of documented response (PR or better)
Measure:Duration of Response (DoR)
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description:Time from first documentation of response (PR or better) to first documentation of PD or death due to any cause
Measure:Time to next antimyeloma treatment (TTNT)
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description:Time from first study treatment (whichever is given earlier) start date to first day when participant receives another antimyeloma treatment
Measure:Progression-free survival after next antimyeloma therapy (PFS2)
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description: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.
Measure:Feasibility of maintenance therapy in combination with bb2121
Time Frame:Up to 4 months after bb2121 infusion in the respective cohort
Safety Issue:
Description:Cumulative incidence of the maintenance therapy starting from bb2121 infusion with death as the competing risk
Measure:Pharmacokinetics - Cmax_Phase 1 and 2
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description:Maximum transgene level
Measure:Pharmacokinetics - Tmax_Phase 1 and 2
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description:Time to maximum observed transgene level
Measure:Pharmacokinetics - AUC_Phase 1 and 2
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description:Area under the curve of transgene level
Measure:Pharmacokinetics - AUC0-28days _Phase 1 and 2
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description:Area under the curve of transgene level from time 0 to 28 days
Measure:Pharmacokinetics - Tlast _Phase 1 and 2
Time Frame:Up to 24 months after the last participant received any study treatment in the respective cohort
Safety Issue:
Description:Time of last measurable transgene level

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Trial 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

Last Updated

August 20, 2021