Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma (MM)

AbbVie

Status and phase: Active, not recruiting; Phase 2

Conditions: Multiple Myeloma

Treatments: Drug: Venetoclax; Drug: Carfilzomib; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT02899052

M15-538

2019-004340-30 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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120 participants in 1 patient group

Venetoclax + Carfilzomib + Dexamethasone

Experimental group

Description:

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

Treatment:

Drug: Dexamethasone

Drug: Carfilzomib

Drug: Venetoclax