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.
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
Interventions
Drug | Synonyms | Arms |
---|
BB2121 | ide-cel | Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone) |
CC-220 | | Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone) |
BMS-986405 | JSMD194 | Arm B- bb2121 in combination with BMS-986405 (JSMD194) |
Pomalidomide | | Arm C-bb2121 in combination with Daratumumab+pomalidomide+low-dose dexamethasone or POM +bortezomib |
Dexamethasone | | Arm C-bb2121 in combination with Daratumumab+pomalidomide+low-dose dexamethasone or POM +bortezomib |
Bortezomib | | Arm 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
Name | Type | Description | Interventions |
---|
Arm A- bb2121 in combination with CC-220 (± low-dose dexamethasone) | Experimental | 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. | |
Arm B- bb2121 in combination with BMS-986405 (JSMD194) | Experimental | 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. | |
Arm C-bb2121 in combination with Daratumumab+pomalidomide+low-dose dexamethasone or POM +bortezomib | Experimental | 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 | - 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