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NCT Number: NCT02899052

Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Participants 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.

Part 4 of this study is currently enrolling.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Multiple Myeloma Blood Protein Disorders Cardiovascular Diseases Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Border Medical Oncology Research Unit Albury Wodonga Regiona /ID# 222200, East Albury, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Carfilzomib

Drug

Carfilzomib lyophilized administered intravenously as a 10 to 30 minute infusion in Cycles 1 and beyond within 30 minutes to 4 hours after dexamethasone dosing.

Dose level 1 (K1) Cycle 1: 20 mg/m2 on Days 1 and 2, 27 mg/m2 on Days 8, 9, 15, and 16; Cycles 2 - 12: 27 mg/m2 on Days 1, 2, 8, 9, 15, and 16; Cycles 13 - 18: 27 mg/m2 on Days 1, 2, 15, and 16; Cycles 19 and beyond, for participants that have not previously transitioned to monotherapy: 27 mg/m2 on Days 1, 2, 15, and 16.

Dose Level K2: Cycle 1: 20 mg/m2 on Day 1; 70 mg/m2 on Days 8 and 15 Cycles 2 - onward: 70 mg/m2 on Days 1, 8, and 15. Dose Level K3: Cycle 1: 20 mg/m2 on Days 1 and 2; 56 mg/m2 on Days 8, 9, 15, and 16.

Cycles 2 - onward: 56 mg/m2 on Days 1, 2, 8, 9, 15, and 16.

Other names: Kyprolis

Venetoclax

Drug

Venetoclax tablet administered orally once daily during Cycles 1 - onward. Venetoclax dose level 1 (Ven1) 400 mg once daily, Ven2 800 mg once daily.

Other names: Venclexta, ABT-199

Dexamethasone

Drug

Dexamethasone tablet administered orally during Cycles 1 - onward. Dexamethasone dose level 1 (Dex1) 40 mg once weekly, Dex2 40 mg once weekly, Dex3 20 mg twice weekly.

Primary outcomes

  1. 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)

    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.

  2. Very Good Partial Response (VGPR) or Better Response Rate of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM

    Time frame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years)

    VGPR or better response rate is defined as the percentage of participants with documented VGPR or better based on IMWG criteria.

  3. Objective Response Rate (ORR) of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM

    Time frame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years)

    ORR is defined as the percentage of participants with a documented PR or better based on IMWG criteria.

  4. Complete Response (CR) or Better Rate of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM

    Time frame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years)

    Complete response or better rate is defined as the percentage of participants with documented CR or better based on IMWG criteria.

Secondary outcomes

  1. 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

    VGPR or better response rate is defined as the proportion of participants with documented VGPR or better based on IMWG criteria.

  2. 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

    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.

  3. 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])

    MRD in the bone marrow by next generation sequencing.

  4. 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

    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.

  5. 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

    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.

  6. 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

    ORR is defined as the proportion of participants with documented partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria.

  7. 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

    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).

  8. 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

    AUC0-24 post-dose of venetoclax.

  9. Clearance (CL) of Carfilzomib

    Time frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15

    CL of carfilzomib.

  10. Terminal Phase Elimination Rate Constant (β) of Carfilzomib

    Time frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15

    β of carfilzomib.

  11. AUC from 0 to Infinity (AUC∞) of Carfilzomib

    Time frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15

    AUC∞ of carfilzomib.

  12. 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

    AUCt of carfilzomib.

  13. Maximum Plasma Concentration (Cmax) of Venetoclax

    Time frame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15

    Cmax of venetoclax.

  14. Cmax of Carfilzomib

    Time frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15

    Cmax of carfilzomib.

  15. Terminal Elimination Half-life (t1/2) of Carfilzomib

    Time frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15

    t1/2 of carfilzomib.

  16. Time to Maximum Plasma Concentration (Peak Time, Tmax) of Venetoclax

    Time frame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15

    (Peak time, Tmax) of venetoclax.

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Collaborators

  • Genentech, Inc; Onyx Therapeutics, Inc.

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2027
Study completion
2027
First posted
Sep 14, 2016
Registry last updated
Aug 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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