An Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma (KarMMa-2)

  • STATUS
    Recruiting
  • End date
    Dec 30, 2030
  • participants needed
    235
  • sponsor
    Celgene
Updated on 10 July 2022
measurable disease
maintenance therapy
cell transplantation
serum proteins
induction therapy
dexamethasone
lenalidomide
electrophoresis
proteasome inhibitor
refractory multiple myeloma
immunotherapeutic agent

Summary

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 235 subjects will be enrolled into one of three cohorts. Cohort 1 will enroll approximately 97 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. Cohort 3 will enroll approximately 30 newly diagnosed multiple myeloma (NDMM) participants with suboptimal response to ASCT.

Description

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

Details
Condition Multiple Myeloma
Treatment bb2121, Lenalomide
Clinical Study IdentifierNCT03601078
SponsorCelgene
Last Modified on10 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study
Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
For Cohorts 1 and 2 only, participant 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
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
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
c: 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. Cohort 3 participants with newly diagnosed MM
(NDMM) who received only induction and ASCT, without subsequent consolidation or
maintenance Subject with NDMM who have received only induction and ASCT, without
subsequent consolidation or maintenance Cohort 3
With NDMM who have received only induction and ASCT, without subsequent
consolidation or maintenance
Must have received 4 to 6 cycles of induction therapy which must contain at
minimum, a proteasome inhibitor and an immunomodulatory agent and must have had
single ASCT within 6 months prior to consent
Must have achieved documented PR or VGPR at first post-ASCT assessment
approximately 100 days after ASCT and this response must be maintained at
screening
Per Investigator's assessment, subject must be a candidate for single-agent
lenalidomide maintenance
Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
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
Plasmapheresis
Major surgery (as defined by the investigator)
Radiation therapy other than local therapy for myeloma associated bone lesions
Use of any systemic anti-myeloma drug therapy
Subject with known central nervous system involvement with myeloma
History or presence of clinically relevant central nervous system (CNS) pathology
Subject used any investigational agents within 14 days prior to leukapheresis or, for
Ongoing treatment with chronic immunosuppressants
Cohort 3, within 14 days prior to consent
Subject received any of the following within the last 14 days prior to leukapheresis
Subject has received ASCT within 12 weeks prior to leukapheresis
or, for Cohort 3, within 14 days prior to consent
Subject has history of primary immunodeficiency
Pregnant or lactating women
Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular
coagulation
Subject with active or history of plasma cell leukemia, Waldenstrom's
macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis
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
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
Subject is positive for human immunodeficiency virus (HIV-1), chronic or active
hepatitis B or active hepatitis A or C
Subject has uncontrolled systemic fungal, bacterial, viral or other infection
(including tuberculosis) despite appropriate antibiotics or other treatment
Subject with prior history of malignancies, other than MM, unless the subject has been
free of the disease for ≥ 5 years
Subject with known hypersensitivity to any component of bb2121 product
cyclophosphamide, fludarabine, and/or tocilizumab
Clear my responses

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