Description:
A Phase 2, open-label, dose escalation study to evaluate the safety and efficacy of
venetoclax in combination with carfilzomib-dexamethasone (Kd) in participants with relapsed
or refractory MM and have received 1 to 3 prior lines of therapy.
Part 4 of this study is currently enrolling.
Title
- Brief Title: Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma (MM)
- Official Title: A Phase 2, Open-Label, Multi-Center Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Clinical Trial IDs
- ORG STUDY ID:
M15-538
- SECONDARY ID:
2019-004340-30
- NCT ID:
NCT02899052
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Carfilzomib | Kyprolis | Venetoclax + Carfilzomib + Dexamethasone |
Venetoclax | Venclexta, ABT-199 | Venetoclax + Carfilzomib + Dexamethasone |
Dexamethasone | | Venetoclax + Carfilzomib + Dexamethasone |
Purpose
A Phase 2, open-label, dose escalation study to evaluate the safety and efficacy of
venetoclax in combination with carfilzomib-dexamethasone (Kd) in participants with relapsed
or refractory MM and have received 1 to 3 prior lines of therapy.
Part 4 of this study is currently enrolling.
Trial Arms
Name | Type | Description | Interventions |
---|
Venetoclax + Carfilzomib + Dexamethasone | Experimental | Part 1: Evaluate the safety and pharmacokinetic profiles while providing information to determine the appropriate doses of venetoclax and carfilzomib (VenKd) to be used in the VenKd combination in approximately 18 participants. The dose levels are Venetoclax 400 mg or 800 mg; Carfilzomib 20/27 mg/m2, 20/70 mg/m2, and/or 20/56 mg/m2; Dexamethasone 40 mg
Part 2: Further evaluate the safety and efficacy profile of the VenKd combination selected after completion of Part 1 in approximately 22 additional participants. Participants may discontinue Kd but may continue receiving venetoclax once daily (QD) as monotherapy.
Part 3: Further evaluation of the efficacy of the VenKd combination after completion of Part 1 and Part 2 in 7 additional participants.
Part 4, An additional 65 participants t(11;14) positive will receive varying doses of the VenKd combination or carfilzomib and dexamethasone | - Carfilzomib
- Venetoclax
- Dexamethasone
|
Eligibility Criteria
Inclusion Criteria:
- Eastern Collaborative Oncology Group (ECOG) performance score of less than or equal to
2.
- Documented relapsed or progressive Multiple Myeloma (MM) on or after any regimen or is
refractory to the most recent line of therapy.
- Positive for translocation t(11;14) as determined by an analytically validated
Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.
- Received prior treatment with at least 1 prior line of therapy for MM.
- Measurable disease on Screening per International Myeloma Working Group (IMWG)
criteria.
- Meets absolute neutrophil count, platelet count, hemoglobin, liver and kidney function
laboratory values within 2 weeks prior to first dose of study drug.
Exclusion Criteria:
- Has a pre-existing condition that is contraindicated including.
- Non-secretory or oligo-secretory MM
- Active plasma cell leukemia.
- Waldenström's macroglobulinemia.
- Primary amyloidosis.
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein,
and skin changes).
- Active hepatitis B or C infection based on screening blood testing.
- Known active Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection.
- Significant cardiovascular disease.
- Major surgery within 4 weeks prior to first dose.
- Acute infections requiring antibiotic, antifungal or antiviral therapy within14
days prior to first dose.
- Peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to
first dose.
- Uncontrolled diabetes or uncontrolled hypertension within 14 days prior to first
dose.
- Any other medical condition that, in the opinion of the Investigator, would
adversely affect the participant's participation in the study.
- History of other active malignancies, including myelodysplastic syndrome (MDS), within
the past 3 years prior to study entry Other protocol defined inclusion/exclusion
criteria could apply
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants with Adverse Events |
Time Frame: | First dose of study drug through at least 30 days after end of treatment (approximately 2 years) |
Safety Issue: | |
Description: | An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. |
Secondary Outcome Measures
Measure: | Very Good Partial Response (VGPR) or Better Response Rate in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression |
Time Frame: | Up to approximately 17 months |
Safety Issue: | |
Description: | VGPR or better response rate is defined as the proportion of participants with documented VGPR or better based on IMWG criteria. |
Measure: | Progression-free survival (PFS) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression |
Time Frame: | Up to approximately 17 months |
Safety Issue: | |
Description: | PFS is defined as the number of days from the date of the first dose of study drug to the date of the first documented progressive disease (PD) or death due to any cause, whichever occurs first. |
Measure: | Minimal residual disease (MRD) |
Time Frame: | Up to 2 years (Screening, Cycle 3 Day 1, and Confirmation of Stringent Complete Response [sCR]/Complete Response [CR]) |
Safety Issue: | |
Description: | MRD in the bone marrow by next generation sequencing. |
Measure: | Duration of Overall Response (DOR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression |
Time Frame: | Up to approximately 17 months |
Safety Issue: | |
Description: | DOR is defined as the number of days from the participant's date of first documented response (PR or better) to the date of first documented PD or death due to MM, whichever occurs first. |
Measure: | Time to progression (TTP) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression |
Time Frame: | Up to approximately 17 months |
Safety Issue: | |
Description: | TTP is defined as the number of days from the date of the first dose of study drug to the date of first documented PD or death due to MM, whichever occurs first. |
Measure: | Objective response rate (ORR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression |
Time Frame: | Up to approximately 17 months |
Safety Issue: | |
Description: | ORR is defined as the proportion of participants with documented partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria. |
Measure: | Time to Response (TTR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression |
Time Frame: | Up to approximately 17 months |
Safety Issue: | |
Description: | TTR is defined as the number of days from the date of the first dose of study drug to the date of first documented response (Partial Response (PR) or better). |
Measure: | Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of Venetoclax |
Time Frame: | Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 |
Safety Issue: | |
Description: | AUC0-24 post-dose of venetoclax. |
Measure: | Clearance (CL) of Carfilzomib |
Time Frame: | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
Safety Issue: | |
Description: | CL of carfilzomib. |
Measure: | Terminal Phase Elimination Rate Constant (β) of Carfilzomib |
Time Frame: | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
Safety Issue: | |
Description: | β of carfilzomib. |
Measure: | AUC from 0 to Infinity (AUC∞) of Carfilzomib |
Time Frame: | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
Safety Issue: | |
Description: | AUC∞ of carfilzomib. |
Measure: | AUC from Time 0 to the Time of the Last Measurable Concentration (AUCt) of Carfilzomib |
Time Frame: | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
Safety Issue: | |
Description: | AUCt of carfilzomib. |
Measure: | Maximum Plasma Concentration (Cmax) of Venetoclax |
Time Frame: | Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 |
Safety Issue: | |
Description: | Cmax of venetoclax. |
Measure: | Cmax of Carfilzomib |
Time Frame: | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
Safety Issue: | |
Description: | Cmax of carfilzomib. |
Measure: | Terminal Elimination Half-life (t1/2) of Carfilzomib |
Time Frame: | Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 |
Safety Issue: | |
Description: | t1/2 of carfilzomib. |
Measure: | Time to Maximum Plasma Concentration (Peak Time, Tmax) of Venetoclax |
Time Frame: | Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 |
Safety Issue: | |
Description: | (Peak time, Tmax) of venetoclax. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | AbbVie |
Trial Keywords
- Multiple Myeloma
- Refractory myeloma
- Relapsed myeloma
- Relapsed or Refractory
Last Updated
August 2, 2021