Clinical Trials /

Study of the Bruton's Tyrosine Kinase Inhibitor in Combination With Carfilzomib (Kyprolis™) in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma

NCT01962792

Description:

Phase 1 will be an open-label study. The dose escalation portion of the study is designed to establish the MTD of ibrutinib in combination with carfilzomib with or without dexamethasone. Phase 2b will be an open-label, multicenter study designed to evaluate the overall response rate when ibrutinib is administered in combination with carfilzomib and dexamethasone.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of the Bruton's Tyrosine Kinase Inhibitor in Combination With Carfilzomib (Kyprolis™) in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
  • Official Title: A Multicenter Phase 1/2b Study of the Bruton's Tyrosine Kinase Inhibitor, Ibrutinib (PCI-32765), in Combination With Carfilzomib (Kyprolis™) in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: PCYC-1119-CA
  • SECONDARY ID: PCI-32765 [Sponsor]
  • NCT ID: NCT01962792

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
IbrutinibPhase 1 - Dose Finding
CarfilzomibPhase 1 - Dose Finding
DexamethasonePhase 1 - Dose Finding

Purpose

Phase 1 will be an open-label study. The dose escalation portion of the study is designed to establish the MTD of ibrutinib in combination with carfilzomib with or without dexamethasone. Phase 2b will be an open-label, multicenter study designed to evaluate the overall response rate when ibrutinib is administered in combination with carfilzomib and dexamethasone.

Detailed Description

      Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoietic cells other than
      T cells and is necessary for downstream signal transduction from various hematopoietic
      receptors including the B cell receptor as well as some Fc, chemokine, and adhesion
      receptors, and is crucial for both B cell development and osteoclastogenesis. Although
      down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from
      many myeloma patients and some cell lines. PCI-32765 is a potent and specific inhibitor of
      Btk currently in Phase 2 and 3 clinical trials. The current study is designed and intended to
      determine the safety and efficacy of PCI-32765 in combination with carfilzomib (Kyprolis™)
      with and without dexamethasone in subjects with relapsed or relapsed and refractory multiple
      myeloma (MM).
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 - Dose FindingExperimentalIbrutinib PO + Carfilzomib IV + Dexamethasone PO
  • Ibrutinib
  • Carfilzomib
  • Dexamethasone
Phase 2b - Main StudyExperimentalIbrutinib PO + Carfilzomib IV + Dexamethasone PO
  • Ibrutinib
  • Carfilzomib
  • Dexamethasone
Phase 2b - Sub-studyExperimentalIbrutinib PO + Carfilzomib IV + Dexamethasone PO
  • Ibrutinib
  • Carfilzomib
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Measurable disease of MM as defined by at least ONE of the following:

               1. Serum monoclonal protein (SPEP) ≥1 g/dL

               2. Urine M-protein ≥200 mg/24 hrs

               3. Serum free light chain (SFLC): involved FLC ≥10 mg/dL (≥100 mg/L) AND abnormal
                  kappa to lambda serum free light chain ratio

          -  Relapsed or relapsed and refractory MM after receiving at least 2 previous therapies,
             including an immunomodulator and bortezomib and had either no response or documented
             disease progression (according to IMWG criteria) to the most recent treatment regimen

          -  Adequate hematologic, hepatic, and renal function

          -  ECOG performance status of 0-2

        Inclusion Criteria for Phase 2 Sub-study Cohort:

          -  Must meet all inclusion criteria defined in main study and in addition the following
             criteria must be met:

          -  Subject must have received a regimen containing carfilzomib in combination with
             dexamethasone as their most recent line of therapy and have:

               1. Achieved less than a partial response (<PR) following at least 4 cycles and are
                  without evidence of progression disease (PD).

                  OR

               2. Disease progression following an initial confirmed response of MR or better to
                  the combination (according to IMWG response criteria).

        Exclusion Criteria:

          -  Subject must not have primary refractory disease

          -  Plasma cell leukemia, primary amyloidosis or POEMS syndrome

          -  Unable to swallow capsules or disease significantly affecting gastrointestinal
             function

          -  Requires anti-coagulation with warfarin or a vitamin K antagonist

          -  Requires treatment with strong CYP3A inhibitors

        Exclusion Criteria for Phase 2 Sub-study Cohort:

          -  Must not meet any exclusion criteria defined in main study except for exclusion
             criteria "Subject must not have primary refractory disease" which is related to prior
             carfilzomib
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1
Time Frame:1 year
Safety Issue:
Description:To determine the maximum tolerated dose (MTD) of ibrutinib in combination with carfilzomib with and without dexamethasone and the recommended phase 2 dose. To describe the toxicities associated with the combination of ibrutinib and carfilzomib with and without dexamethasone in subjects with relapsed or relapsed and refractory multiple myeloma (MM).

Secondary Outcome Measures

Measure:Phase 1
Time Frame:1 year
Safety Issue:
Description:Overall response rate (ORR). Duration of Response (DOR).
Measure:Phase 2b
Time Frame:1 year
Safety Issue:
Description:PFS rates at landmark points from start of treatment. DOR. Overall survival (OS). Time to progression (TTP). To evaluate the safety and tolerability of ibrutinib in combination with carfilzomib and dexamethasone.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pharmacyclics LLC.

Trial Keywords

  • PCI-32765
  • Multiple Myeloma
  • Relapsed Refractory Multiple Myeloma
  • Bruton's Tyrosine Kinase
  • Carfilzomib
  • Dexamethasone
  • Ibrutinib

Last Updated

May 23, 2017