A Phase 1, Open-label, Multicenter Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (KarMMa-4)
Overview
- Phase
- Phase 1
- Intervention
- bb2121
- Conditions
- Multiple Myeloma
- Sponsor
- Celgene
- Enrollment
- 13
- Locations
- 22
- Primary Endpoint
- Adverse Events (AEs)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a multicenter, open-label, phase 1, single arm study intended to determine the optimal target dose and safety of bb2121 in subjects with HR (R-ISS Stage III per IMWG criteria) NDMM. Subjects should have received 3 Cycles of standard induction therapy prior to undergoing leukapheresis procedure to collect autologous mononuclear cells for manufacture of the drug product (bb2121). Following manufacture of the drug product, subjects will receive fourth cycle of induction therapy followed by lymphodepleting therapy with fludarabine and cyclophosphamide prior to bb2121 infusion. Maintenance therapy is recommended for all subjects who have received bb2121 infusion and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must satisfy all of the following criteria to be enrolled in the study:
- •Subject is newly diagnosed and has symptomatic Multiple Myeloma (MM) prior to initiating induction anti-myeloma therapy
- •Subject is ≥ 18 years of age at the time of initial diagnosis of MM
- •Subject has measurable disease at initial diagnosis by
- •M-protein and/or
- •Light chain MM without measurable disease in the serum or urine
- •Subject has high-risk MM at the time of initial diagnosis of MM per R-ISS Stage III as defined by IMWG:
- •ISS Stage III and cytogenetic abnormalities with t(4; 14) and/or del(17p); and/or t(14:16) by iFISH; or;
- •ISS Stage III and serum LDH \> ULN
- •Subject has Eastern Cooperative Oncology Group performance ≤ 1
Exclusion Criteria
- •The presence of any of the following will exclude a subject from enrollment: The presence of any of the following will exclude a subject from enrollment:
- •At initial diagnosis, screening and prior to initiation of induction therapy for MM:
- •Subject has non-secretory MM
- •During Screening:
- •Subject received any treatments for MM other than up to 3 cycles of induction therapy per protocol
- •Subject has any of the following laboratory abnormalities:
- •Absolute neutrophil count \< 1,000/μL
- •Platelet count \< 50,000 mm3
- •Hemoglobin \< 8 g/dL (\< 4.9 mmol/L)
- •Serum creatinine clearance \< 45 mL/min
Arms & Interventions
Dose Escalation
* bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 800 x 10\^6 CAR+ T cells after receiving lymphodepleting chemotherapy with a planned starting dose of 450 x 10\^6 CAR+ T cells. * Lenalidomide maintenance therapy is recommended for all patients and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later
Intervention: bb2121
Dose Escalation
* bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 800 x 10\^6 CAR+ T cells after receiving lymphodepleting chemotherapy with a planned starting dose of 450 x 10\^6 CAR+ T cells. * Lenalidomide maintenance therapy is recommended for all patients and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later
Intervention: Fludarabine
Dose Escalation
* bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 800 x 10\^6 CAR+ T cells after receiving lymphodepleting chemotherapy with a planned starting dose of 450 x 10\^6 CAR+ T cells. * Lenalidomide maintenance therapy is recommended for all patients and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later
Intervention: Cyclophosphamide
Dose Escalation
* bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 800 x 10\^6 CAR+ T cells after receiving lymphodepleting chemotherapy with a planned starting dose of 450 x 10\^6 CAR+ T cells. * Lenalidomide maintenance therapy is recommended for all patients and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later
Intervention: Lenalidomide
Outcomes
Primary Outcomes
Adverse Events (AEs)
Time Frame: Approximately 2 years after last subject bb2121 infused
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject 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 subject'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.
Dose-limiting toxicity (DLT) rates
Time Frame: Up to completion of DLT period after last subject bb2121 infused
DLTs will be assessed during the DLT interval (ie, within 21 days immediately after bb2121 infusion). DLTs are defined as any bb2121 related Grade 3 to 5 toxicity.
Secondary Outcomes
- Pharmacokinetics - Cmax(Approximately 2 years after last subject bb2121 infused)
- Proportion of subjects who achieved Complete Response (CR) Rate(Approximately 2 years after last subject bb2121 infused)
- Duration of Response (DoR)(Approximately 2 years after last subject bb2121 infused)
- Feasibility of initiating maintenance(Approximately 2 years after last subject bb2121 infused)
- Overall Response Rate (ORR)(Approximately 2 years after last subject bb2121 infused)
- Time to Complete Response (TCR)(Approximately 2 years after last subject bb2121 infused)
- Time to start maintenance(Approximately 2 years after last subject bb2121 infused)
- Progression-free Survival (PFS)(Approximately 2 years after last subject bb2121 infused)
- Overall Survival (OS)(Approximately 2 years after last subject bb2121 infused)
- Pharmacokinetics - Tmax(Approximately 2 years after last subject bb2121 infused)
- Pharmacokinetics - AUC(Approximately 2 years after last subject bb2121 infused)