Clinical Trials /

An Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma

NCT03601078

Description:

This study is a multi-cohort, open-label, multicenter Phase 2 study to evaluate the efficacy and safety of bb2121 in subjects with relapsed and refractory MM (Cohort 1), in subjects with MM having progressed within one 18 months of initial treatment including autologous stem cell transplantation (ASCT) (Cohort 2a), and without ASCT (Cohort 2b) or, in subjects with inadequate response post ASCT during initial treatment (Cohort 2c) Approximately 181 subjects will be enrolled into one of two cohorts. Cohort 1 will enroll approximately 73 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens. Cohort 2a will enroll approximately 39 MM subjects, with 1 prior anti-myeloma therapy including ASCT and with early relapse. Cohort 2b will enroll approximately 39 MM subjects with 1 prior anti-myeloma therapy not including ASCT and with early relapse. Cohort 2c will enroll approximately 30 MM subjects with inadequate response to ASCT during their initial anti-myeloma therapy. The cohorts will start in parallel and independently.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: An Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma
  • Official Title: A Phase 2, Multicohort, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With Clinical High-Risk Multiple Myeloma (KarMMa-2)

Clinical Trial IDs

  • ORG STUDY ID: BB2121-MM-002
  • SECONDARY ID: U1111-1216-4209
  • SECONDARY ID: 2018-000264-28
  • NCT ID: NCT03601078

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
bb2121bb2121 in relapsed and refractory multiple myeloma patients

Purpose

This study is a multi-cohort, open-label, multicenter Phase 2 study to evaluate the efficacy and safety of bb2121 in subjects with relapsed and refractory MM (Cohort 1), in subjects with MM having progressed within one 18 months of initial treatment including autologous stem cell transplantation (ASCT) (Cohort 2a), and without ASCT (Cohort 2b) or, in subjects with inadequate response post ASCT during initial treatment (Cohort 2c) Approximately 181 subjects will be enrolled into one of two cohorts. Cohort 1 will enroll approximately 73 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens. Cohort 2a will enroll approximately 39 MM subjects, with 1 prior anti-myeloma therapy including ASCT and with early relapse. Cohort 2b will enroll approximately 39 MM subjects with 1 prior anti-myeloma therapy not including ASCT and with early relapse. Cohort 2c will enroll approximately 30 MM subjects with inadequate response to ASCT during their initial anti-myeloma therapy. The cohorts will start in parallel and independently.

Detailed Description

      Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being
      manufactured for cohorts 1, 2a and 2b only.
    

Trial Arms

NameTypeDescriptionInterventions
bb2121 in relapsed and refractory multiple myeloma patientsExperimentalbb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 450 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy
  • bb2121

Eligibility Criteria

        Inclusion Criteria:

        Subjects must satisfy the following criteria to be enrolled in the study:

          1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)

          2. Subject has measurable disease, defined as:

               -  M-protein (serum protein electrophoresis [sPEP] or urine protein electrophoresis
                  [uPEP]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or

               -  Light chain MM without measurable disease in the serum or urine: Serum
                  immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin
                  kappa lambda free light chain ratio

          3. Subjects with one of the following cohort specific requirements:

             Cohort 1 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens:

               -  Subject must have received at least 3 prior anti-myeloma treatment regimens.
                  Note: induction with or without hematopoietic stem cell transplant and with or
                  without maintenance therapy is considered a single regimen

               -  Subject must have undergone at least 2 consecutive cycles of treatment for each
                  regimen, unless PD was the best response to the regimen

               -  Subject must have received prior treatment with a proteasome inhibitor, an
                  immunomodulatory agent and an anti-CD38 antibody

               -  Subject has evidence of PD on or within 60 days of the most recent prior
                  treatment regimen

               -  Subject achieved a response (minimal response [MR] or better) to at least 1 prior
                  treatment regimen

             Cohort 2 subjects with 1 prior anti-myeloma treatment regimen:

               -  Subject must have received only 1 prior anti-myeloma treatment regimen. Note:
                  induction with or without hematopoietic stem cell transplant and with or without
                  maintenance therapy is considered a single regimen

               -  Subject must have the following HR factors:

                  - R-ISS stage III AND

               -  Early relapse defined as:

             Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must
             contain induction, ASCT (single or tandem) and lenalidomide containing maintenance.

             Cohort 2b: PD < 18 months since date of start or initial therapy which must contain at
             minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone Cohort
             2c: Subject must have received minimum 3 cycles of induction therapy which must
             contain at minimum, a proteasome inhibitor, an immunomodulatory agent and
             dexamethasone. Subjects must have had ASCT (single or tandem AND < VGPR (excluding PD)
             at first assessment between 70 to 110 days after last ASCT, with initial therapy
             without consolidation and maintenance.

          4. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

          5. Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities
             due to prior treatments, excluding alopecia and Grade 2 neuropathy

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from enrollment:

          1. Subject used any investigational agents within 14 days of leukapheresis

          2. Subject received any of the following within the last 14 days of leukapheresis:

               1. Plasmapheresis

               2. Major surgery (as defined by the investigator)

               3. Radiation therapy other than local therapy for myeloma associated bone lesions

               4. Use of any systemic anti-myeloma drug therapy

          3. Subject with known central nervous system involvement with myeloma

          4. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular
             coagulation

          5. History or presence of clinically relevant central nervous system (CNS) pathology

          6. Subject with active or history of plasma cell leukemia, Waldenstrom's
             macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis

          7. Inadequate organ function Subject with a history of Class III or IV congestive heart
             failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled
             angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months
             prior to starting study treatment

          8. Ongoing treatment with chronic immunosuppressants

          9. Previous history of an allogeneic hematopoietic stem cell transplantation or treatment
             with any gene therapy-based therapeutic for cancer or investigational cellular therapy
             for cancer or BCMA targeted therapy

         10. Subject has received ASCT within 12 weeks prior to leukapheresis

         11. Subject has history of primary immunodeficiency

         12. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active
             hepatitis B or active hepatitis A or C

         13. Subject has uncontrolled systemic fungal, bacterial, viral or other infection
             (including tuberculosis) despite appropriate antibiotics or other treatment

         14. Subject with prior history of malignancies, other than MM, unless the subject has been
             free of the disease for ≥ 5 years

         15. Pregnant or lactating women

         16. Subject with known hypersensitivity to any component of bb2121 product,
             cyclophosphamide, fludarabine, and/or tocilizumab
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)- Cohort 1
Time Frame:Minimum of 2 years after bb2121 infusion
Safety Issue:
Description:Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an independent response committee (IRC)

Secondary Outcome Measures

Measure:Complete response (CR) rate - Cohort 1
Time Frame:Minimum of 2 years after bb2121 infusion
Safety Issue:
Description:Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC
Measure:Overall response rate (ORR) - Cohort 2a, b and c
Time Frame:Minimum of 2 years after bb2121 infusion
Safety Issue:
Description:Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC
Measure:Time to response (TTR)
Time Frame:Minimum of 2 years after bb2121 infusion
Safety Issue:
Description:Time from first bb2121 infusion to first documentation of response (PR or greater)
Measure:Duration of response (DoR)
Time Frame:Minimum of 2 years after bb2121 infusion
Safety Issue:
Description:Time from first documentation of response (PR or greater) to first documentation of progressive disease (PD) or death from any cause, whichever occurs first
Measure:Progression-free survival (PFS)
Time Frame:Minimum of 2 years after bb2121 infusion
Safety Issue:
Description:Time from first bb2121 infusion to first documentation of PD, or death due to any cause, whichever occurs first
Measure:Time to progression (TTP)
Time Frame:Minimum of 2 years after bb2121 infusion
Safety Issue:
Description:Time from first bb2121 infusion to first documentation of PD
Measure:Overall survival (OS)
Time Frame:Minimum of 2 years after bb2121 infusion
Safety Issue:
Description:Time from first bb2121 infusion to time of death due to any cause
Measure:Adverse Events (AEs)
Time Frame:Minimum 5 years after bb2121 infusion
Safety Issue:
Description:Type, frequency, seriousness and severity of adverse events (AEs), adverse events of special interest (AESIs) (including cytokine release syndrome, neurotoxicity and infection), and relationship of AE to study drug.
Measure:Pharmacokinetics - Cmax
Time Frame:Minimum 5 years after bb2121 infusion
Safety Issue:
Description:Maximum expansion of bb2121 chimeric antigen receptor (CAR) T cells
Measure:Pharmacokinetics - tmax
Time Frame:Minimum 5 years after bb2121 infusion
Safety Issue:
Description:Time to peak of bb2121 CAR T cells
Measure:Pharmacokinetics - AUC
Time Frame:Minimum 5 years after bb2121 infusion
Safety Issue:
Description:Area under the curve of CAR T cells
Measure:Pharmacokinetics - tlast
Time Frame:Minimum 5 years after bb2121 infusion
Safety Issue:
Description:Time to last measurable CAR T cells
Measure:Pharmacokinetics - AUC0-28days
Time Frame:Minimum 5 years after bb2121 infusion
Safety Issue:
Description:Area under the curve of CAR T cells from time zero to Day 28
Measure:Immunogenicity
Time Frame:Minimum of 2 years after bb2121 infusion
Safety Issue:
Description:Development of an anti-CAR antibody response
Measure:Minimal Residual Disease (MRD) negative rate
Time Frame:Minimum of 2 years after bb2121 infusion
Safety Issue:
Description:Proportion of subjects that are MRD negative
Measure:Subject-reported outcomes as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30)
Time Frame:Minimum 5 years after bb2121 infusion
Safety Issue:
Description:Questionnaire will be used as a measure of health-related quality of life
Measure:Subject-reported outcomes as measured by EuroQoL Group EQ-5D-5L Health Questionnaire
Time Frame:Minimum 5 years after bb2121 infusion
Safety Issue:
Description:Is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal
Measure:Subject-reported outcomes as measured by EORTC-QLQ-MY20
Time Frame:Minimum 5 years after bb2121 infusion
Safety Issue:
Description:Is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality
Measure:Very good partial response (VGPR) rate - Cohort 2c
Time Frame:Minimum of 2 years after bb2121 infusion
Safety Issue:
Description:Percentage of subjects who achieved VGPR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC

Details

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

Trial Keywords

  • Multiple Myeloma
  • bb2121
  • Relapsed and Refractory Multiple Myeloma
  • High Risk Multiple Myeloma

Last Updated

January 10, 2020