KarMMa-7: Safety and Efficacy of bb2121 (Ide-cel) Combinations in Multiple Myeloma

Sponsor
Celgene (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04855136
Collaborator
(none)
415
Enrollment
24
Locations
3
Arms
58.6
Anticipated Duration (Months)
17.3
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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)

  • 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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
415 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Jun 1, 2021
Anticipated Primary Completion Date :
Nov 24, 2024
Anticipated Study Completion Date :
Apr 20, 2026

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone)

bb2121 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.

Biological: BB2121
CAR T Cell Therapy
Other Names:
  • ide-cel
  • Drug: CC-220
    Cereblon (CRBN) E3 ligase modulatory compound (CELMoD)

    Experimental: Arm B- bb2121 in combination with BMS-986405 (JSMD194)

    bb2121 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.

    Biological: BB2121
    CAR T Cell Therapy
    Other Names:
  • ide-cel
  • Drug: BMS-986405
    gamma secretase inhibitor (GSI)
    Other Names:
  • JSMD194
  • Experimental: Arm C-bb2121 in combination with Daratumumab+pomalidomide+low-dose dexamethasone or POM +bortezomib

    bb2121 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

    Biological: BB2121
    CAR T Cell Therapy
    Other Names:
  • ide-cel
  • Drug: Pomalidomide
    immunomodulatory agent

    Drug: Dexamethasone
    corticosteroids

    Drug: Bortezomib
    inhibitor of the proteasome

    Outcome Measures

    Primary Outcome Measures

    1. Does Limiting Toxicity (DLT) rates _Phase 1 [Up to 28 days from start of the combination therapy]

      Percentage of participants experiencing DLTs

    2. Complete Response Rate (CRR)_ Phase 2 [Up to 24 months]

      Proportion of participants who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by investigator's review

    Secondary Outcome Measures

    1. Incidence of Adverse Event (AEs) [Up to 24 months after the last participant received any study treatment]

      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.

    2. Overall Response Rate (ORR) [Up to 24 months after the last participant received any study treatment in the respective cohort]

      Proportion of participants who achieved PR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed investigator's review

    3. Progression-free Survival (PFS) [Up to 24 months after the last participant received any study treatment in the respective cohort]

      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

    4. Overall Survival (OS) [Up to 24 months after the last participant received any study treatment in the respective cohort]

      Time from first study treatment (whichever is given earlier) start date to death due to any cause

    5. Time to response (TTR) [Up to 24 months after the last participant received any study treatment in the respective cohort]

      Time from first study treatment start date to the first date of documented response (PR or better)

    6. Duration of Response (DoR) [Up to 24 months after the last participant received any study treatment in the respective cohort]

      Time from first documentation of response (PR or better) to first documentation of PD or death due to any cause

    7. Time to next antimyeloma treatment (TTNT) [Up to 24 months after the last participant received any study treatment in the respective cohort]

      Time from first study treatment (whichever is given earlier) start date to first day when participant receives another antimyeloma treatment

    8. Progression-free survival after next antimyeloma therapy (PFS2) [Up to 24 months after the last participant received any study treatment in the respective cohort]

      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.

    9. Feasibility of maintenance therapy in combination with bb2121 [Up to 4 months after bb2121 infusion in the respective cohort]

      Cumulative incidence of the maintenance therapy starting from bb2121 infusion with death as the competing risk

    10. Pharmacokinetics - Cmax_Phase 1 and 2 [Up to 24 months after the last participant received any study treatment in the respective cohort]

      Maximum transgene level

    11. Pharmacokinetics - Tmax_Phase 1 and 2 [Up to 24 months after the last participant received any study treatment in the respective cohort]

      Time to maximum observed transgene level

    12. Pharmacokinetics - AUC_Phase 1 and 2 [Up to 24 months after the last participant received any study treatment in the respective cohort]

      Area under the curve of transgene level

    13. Pharmacokinetics - AUC0-28days _Phase 1 and 2 [Up to 24 months after the last participant received any study treatment in the respective cohort]

      Area under the curve of transgene level from time 0 to 28 days

    14. Pharmacokinetics - Tlast _Phase 1 and 2 [Up to 24 months after the last participant received any study treatment in the respective cohort]

      Time of last measurable transgene level

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Alabama BirminghamBirminghamAlabamaUnited States10016
    2University of California, San Francisco- CaliforniaSan FranciscoCaliforniaUnited States94143
    3Mayo Clinic - JacksonvilleJacksonvilleFloridaUnited States32224
    4Winship Cancer Institute of Emory UniversityAtlantaGeorgiaUnited States30322
    5Northside Hospital, IncAtlantaGeorgiaUnited States30342
    6Northwestern UniversityChicagoIllinoisUnited States60611
    7University of Maryland - Greenebaum Comprehensive Cancer CenterBaltimoreMarylandUnited States21201
    8Massachusetts General HospitalBostonMassachusettsUnited States02117
    9Beth Israel Deaconess Medical CenterBostonMassachusettsUnited States02215
    10The Cancer Center at Hackensack University Medical CenterHackensackNew JerseyUnited States07601
    11New York University LangoneNew YorkNew YorkUnited States10016
    12Weill Cornell Medicine / New York Presbyterian HospitalNew YorkNew YorkUnited States10021
    13Icahn School of Medicine at Mount Sinai Medical CenterNew YorkNew YorkUnited States10029
    14Columbia University Medical CenterNew YorkNew YorkUnited States10032
    15Levine Cancer InstituteCharlotteNorth CarolinaUnited States28204
    16Duke University Medical CenterDurhamNorth CarolinaUnited States27705
    17Kimmel Cancer Center Thomas Jefferson UnivPhiladelphiaPennsylvaniaUnited States19107
    18Sarah Cannon Research Institute Center for Blood CancersNashvilleTennesseeUnited States37203
    19University of Texas Southwestern Medical CenterDallasTexasUnited States75390
    20The University of Texas - MD Anderson Cancer CenterHoustonTexasUnited States77030
    21Fred Hutchinson Cancer Research CenterSeattleWashingtonUnited States98109
    22University of Wisconsin Medical SchoolMadisonWisconsinUnited States53792
    23Clinica Universidad de NavarraPamplonaSpain31008
    24Universitario de Salamanca - Hospital ClinicoSalamancaSpain37007

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Director: Gianfranco Pittari, Md, PhD, Celgene Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT04855136
    Other Study ID Numbers:
    • BB2121-MM-007
    • 2020-003248-10
    First Posted:
    Apr 22, 2021
    Last Update Posted:
    Sep 16, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Celgene
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 16, 2021