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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01962792
Recruitment Status : Completed
First Posted : October 14, 2013
Last Update Posted : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics LLC.

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Ibrutinib Drug: Carfilzomib Drug: Dexamethasone Phase 1 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 2013
Actual Primary Completion Date : March 2019
Actual Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Phase 1 - Dose Finding
Ibrutinib PO + Carfilzomib IV + Dexamethasone PO
Drug: Ibrutinib
Drug: Carfilzomib
Drug: Dexamethasone
Experimental: Phase 2b - Main Study
Ibrutinib PO + Carfilzomib IV + Dexamethasone PO
Drug: Ibrutinib
Drug: Carfilzomib
Drug: Dexamethasone
Experimental: Phase 2b - Sub-study
Ibrutinib PO + Carfilzomib IV + Dexamethasone PO
Drug: Ibrutinib
Drug: Carfilzomib
Drug: Dexamethasone



Primary Outcome Measures :
  1. Phase 1 [ Time Frame: 1 year ]
    • 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).

  2. Phase 2b [ Time Frame: 1 year ]
    • To evaluate the overall response (ORR) of ibrutinib in combination with carfilzomib and dexamethasone.


Secondary Outcome Measures :
  1. Phase 1 [ Time Frame: Up to 48 months ]
    Overall response rate (ORR).

  2. Phase 1 [ Time Frame: Up to 48 months ]
    Duration of Response (DOR)

  3. Phase 2b [ Time Frame: Up to 3 years ]
    PFS

  4. Phase 2b [ Time Frame: Up to 3 years ]
    DOR

  5. Phase 2b [ Time Frame: Up to 3 years ]
    Overall Survival (OS)

  6. Phase 2b [ Time Frame: Up to 3 years ]
    Time to Progression (TTP)

  7. Phase 2b [ Time Frame: Up to 3 years ]
    Safety and tolerability as measured by the number of adverse events as assessed by CTCAE v4.03



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01962792


Locations
Show Show 17 study locations
Sponsors and Collaborators
Pharmacyclics LLC.
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Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT01962792    
Other Study ID Numbers: PCYC-1119-CA
PCI-32765 [Sponsor]
First Posted: October 14, 2013    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: April 2019
Keywords provided by Pharmacyclics LLC.:
PCI-32765
Multiple Myeloma
Relapsed Refractory Multiple Myeloma
Bruton's Tyrosine Kinase
Carfilzomib
Dexamethasone
Ibrutinib
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents