Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (MM)
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.
- Multiple Myeloma
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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.
- Received prior treatment with at least 1, but no more than 3, prior lines 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.
- For Part 3, Cohort 7, participants must meet the above criteria and also be positive for translocation t(11;14) as determined by an analytically validated Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.
- 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
- 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 subject'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
- Phase 2
- Study Type
- Intervention Model
- Single Group Assignment
- Primary Purpose
- None (Open Label)
Venetoclax + Carfilzomib + Dexamethasone
|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 9-18 subjects. 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 - 31 additional subjects. 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 60 additional subjects.||
- NCT ID