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Clinical Trial 20509

Cancer Type: Immunotherapy
Study Type: Treatment
NCT#: NCT04196491

Phase: Phase I
Prinicipal Investigator: Taiga Nishihori

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Study Title

A Phase 1, Open-Label, Multicenter Study to Evaluate the Safety of BB2121 in Subjects with High Risk, Newly Diagnosed Multiple Myeloma (NDMM) (KarMMa-4)


This is a multicenter, open-label, phase 1, single arm study intended to determine the optimal target dose and safety of bb2121 in patients with HR (R-ISS Stage III per IMWG criteria) NDMM.


Primary Objective: The primary objective of the study is to evaluate the safety and to determine the optimal dose of bb2121 in subjects with HR NDMM. Secondary Objectives: -Evaluate the efficacy of bb2121 in subjects with HR NDMM -Evaluate feasibility of initiating lenalidomide maintenance therapy post-bb2121 infusion -Characterize the expansion of chimeric antigen receptor (CAR) +T cells in the peripheral blood (cellular kinetics - pharmacokinetics [PK]) Exploratory Objectives: -Evaluate safety of lenalidomide maintenance therapy post-bb2121 -Evaluate MRD negative status by NGS -Evaluate exploratory cytokines and chemokines associated with inflammatory cell activation and function before and after infusion of bb2121 -Evaluate biomarkers of disease and antigen burden (eg. BCMA expression in tumor, soluble (s)BCMA in blood) before and after infusion of bb2121 -Evaluate cell subtype and functional phenotypes of CAR T and endogenous immune cells before and after infusion of bb2121 in blood -Evaluate genomic and transcriptomic characteristics of the tumor before and after bb2121 infusion -Evaluate mechanisms of tumor sensitivity/resistance to bb2121 CAR T cell therapy -Evaluate different MM potential prognostic subgroups by assessing genomic characteristics of tumor tissue (eg, TP53 mutation) -Evaluate the immunogenicity of bb2121




Bortezomib (); CC-5013 (Lenalidomide); Daratumumab (Darzalex); Dexamethasone (); Lenalidomide (Revlimid); PS-341 (Bortezomib); Tocilizumab (); Velcade (Bortezomib); bb2121 (); carfilzomib (Kyprolis); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Inclusion Criteria

Inclusion Criteria:

  • Newly diagnosed and has symptomatic Multiple Myeloma (MM) prior to initiating induction anti-myeloma therapy
  • 18 years of age or older at the time of initial diagnosis of MM
  • Has measurable disease at initial diagnosis by (a) M-protein and/or (b) Light chain MM without measurable disease in the serum or urine
  • Has high-risk MM at the time of initial diagnosis of MM per R-ISS Stage III as defined by IMWG: (a) ISS Stage III and cytogenetic abnormalities with t(4; 14) and/or del(17p); and/or t(14:16) by iFISH; or; (b) ISS Stage III and serum LDH > ULN
  • Eastern Cooperative Oncology Group performance ≤ 1
  • Has received ≤ to 3 cycles of the following induction anti-myeloma therapy prior to enrollment: Cycle 1: one of the following regimens (RVd, KRd, CyBorD, D-RVd and D-KRd) Cycle 2 to Cycle 3: either KRd or RVd (Cycle 3 must be without dexamethasone)
  • Other criteria may apply

  • Exclusion Criteria

    Exclusion Criteria:

  • Received any treatments for MM other than up to 3 cycles of induction therapy per protocol
  • Any of the following laboratory anomalies: Absolute neutrophil count 13.5 mg/dL (> 3.4 mmol/L) Serum aspartate aminotransferase or alanine aminotransferase > 2.5 × upper limit of normal Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome INR or aPTT > 1.5 × ULN
  • History or presence of clinically significant CNS pathology
  • Has high risk for developing deep vein thrombosis or pulmonary embolus and are unable or unwilling to undergo anti-thrombotic therapy
  • Has peripheral neuropathy of > Grade 2 severity according to the NCI CTCAE Version 4.03 with bortezomib based induction regimen
  • Has moderate or severe pulmonary hypertension
  • Has intolerance to components of induction regimen (KRd or RVd) or has any contraindication to one or the other drug
  • Has not recovered from induction therapy-related toxicities (non-hematologic) to > Has prior history of deep vein thrombosis or pulmonary embolus (PE) within 6 months of starting study treatment
  • Has cardiac conditions such as (a) Echocardiogram or multi gated acquisition assessment of left ventricular ejection fraction > Has Pulmonary conditions such as: a) known chronic obstructive pulmonary with a forced expiratory vol in 1 sec 50% of predicted normal. (b) Inadequate pulmonary function defined as oxygen saturation > Patient needs ongoing treatment with chronic immunosuppressants
  • History of primary immunodeficiency
  • Patient is seropositive for human immunodeficiency virus, chronic or active hepatitis B or active hepatitis A or C
  • Other exclusions may apply

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