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.
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
Interventions
Drug | Synonyms | Arms |
---|
Ibrutinib | | Phase 1 - Dose Finding |
Carfilzomib | | Phase 1 - Dose Finding |
Dexamethasone | | Phase 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
Name | Type | Description | Interventions |
---|
Phase 1 - Dose Finding | Experimental | Ibrutinib PO + Carfilzomib IV + Dexamethasone PO | - Ibrutinib
- Carfilzomib
- Dexamethasone
|
Phase 2b - Main Study | Experimental | Ibrutinib PO + Carfilzomib IV + Dexamethasone PO | - Ibrutinib
- Carfilzomib
- Dexamethasone
|
Phase 2b - Sub-study | Experimental | Ibrutinib 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: | Up to 48 months |
Safety Issue: | |
Description: | Overall response rate (ORR). |
Measure: | Phase 1 |
Time Frame: | Up to 48 months |
Safety Issue: | |
Description: | Duration of Response (DOR) |
Measure: | Phase 2b |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | PFS |
Measure: | Phase 2b |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | DOR |
Measure: | Phase 2b |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Overall Survival (OS) |
Measure: | Phase 2b |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Time to Progression (TTP) |
Measure: | Phase 2b |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | Safety and tolerability as measured by the number of adverse events as assessed by CTCAE v4.03 |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Pharmacyclics LLC. |
Trial Keywords
- PCI-32765
- Multiple Myeloma
- Relapsed Refractory Multiple Myeloma
- Bruton's Tyrosine Kinase
- Carfilzomib
- Dexamethasone
- Ibrutinib
Last Updated
April 8, 2019