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

This study is currently recruiting participants.
Verified October 2017 by AbbVie
Sponsor:
ClinicalTrials.gov Identifier:
NCT02899052
First Posted: September 14, 2016
Last Update Posted: November 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Genentech, Inc.
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
AbbVie
  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.

Condition Intervention Phase
Relapsed or Refractory Multiple Myeloma Drug: Venetoclax Drug: Dexamethasone Drug: Carfilzomib Phase 2

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Adverse events [ Time Frame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years) ]

Secondary Outcome Measures:
  • Objective response rate (ORR) in participants with relapsed or refractory MM 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.

  • Very Good Partial Response (VGPR) or better response rate in participants with relapsed or refractory MM and in a subset of participants with high 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.

  • Progression-free survival (PFS) in participants with relapsed or refractory MM and in a subset of participants with high 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.

  • Time to progression (TTP) in participants with relapsed or refractory MM and in a subset of participants with high 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.

  • Duration of overall response (DOR) in participants with relapsed or refractory MM and in a subset of participants with high 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.

  • 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.

  • Maximum plasma concentration (Cmax) of venetoclax [ Time Frame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 ]
  • Time to maximum plasma concentration (peak time, Tmax) of venetoclax [ Time Frame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 ]
  • 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 ]
  • Cmax of carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]
  • Terminal phase elimination rate constant (β) of carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]
  • Terminal elimination half-life (t1/2) of carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]
  • 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 ]
  • AUC from 0 to infinity (AUC∞)of carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]
  • Clearance (CL) of carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]

Estimated Enrollment: 40
Actual Study Start Date: January 19, 2017
Estimated Study Completion Date: December 22, 2020
Estimated Primary Completion Date: March 27, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Venetoclax
Venetoclax tablet administered orally once daily during Cycles 1-18. Venetoclax dose level 1 (Ven1) 400 mg once daily, Ven2 800 mg once daily.
Other Name: ABT-199
Drug: Dexamethasone
Dexamethasone tablet administered orally during Cycles 1 - 18. Dexamethasone dose level 1 (Dex1) 40 mg once weekly, Dex2 40 mg once weekly, Dex3 20 mg twice weekly.
Drug: Carfilzomib

Carfilzomib lyophilized administered intravenously as a 10 to 30 minute infusion in Cycles 1 - 18 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.

Dose Level K2: Cycle 1: 20 mg/m2 on Day 1; 70 mg/m2 on Days 8 and 15 Cycles 2 - 18: 70 mg/m2 on Days 1, 8, and 15. Dose Level K3: Cycle 1: 2 mg/m2 on Days 1 and 2; 56 mg/m2 on Days 8, 9, 15, and 16.

Cycles 2 - 18: 56 mg/m2 on Days 1, 2, 8, 9, 15, and 16.

Other Name: Kyprolis

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • 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.

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
  • Significant cardiovascular disease
  • Major surgery within 4 weeks prior to first dose
  • Acute infections requiring parenteral therapy
  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02899052


Contacts
Contact: AbbVie_Call Center 847-283-8955 abbvieclinicaltrials@abbvie.com

Locations
United States, Alabama
UAB Comprehensive Cancer Center /ID# 151405 Recruiting
Birmingham, Alabama, United States, 35294-3300
United States, Arkansas
University of Arkansas for Medical Sciences /ID# 151399 Recruiting
Little Rock, Arkansas, United States, 72205
United States, Illinois
The University of Chicago Medical Center /ID# 151395 Recruiting
Chicago, Illinois, United States, 60637
United States, Kentucky
University of Kentucky Markey Cancer Center /ID# 151407 Recruiting
Lexington, Kentucky, United States, 40536-0293
United States, Maryland
University of Maryland /ID# 159721 Not yet recruiting
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Cape Cod Hospital /ID# 151765 Withdrawn
Hyannis, Massachusetts, United States, 02601
United States, North Carolina
Duke University Medical Center /ID# 162062 Not yet recruiting
Durham, North Carolina, United States, 27710
United States, Pennsylvania
University of Pennsylvania /ID# 151768 Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Utah
Huntsman Cancer Institute /ID# 151397 Recruiting
Salt Lake City, Utah, United States, 84112
United States, Washington
VA Puget Sound Healthcare System /ID# 155369 Not yet recruiting
Seattle, Washington, United States, 98108
Puerto Rico
Auxilio Mutuo Cancer Center /ID# 157853 Recruiting
San Juan, Puerto Rico, 00918
Auxilio Mutuo Cancer Center /ID# 166793 Withdrawn
San Juan, Puerto Rico, 00918
VA Caribbean Healthcare System (VACHS) /ID# 157854 Not yet recruiting
San Juan, Puerto Rico, 00921
Sponsors and Collaborators
AbbVie
Genentech, Inc.
Onyx Therapeutics, Inc.
Investigators
Principal Investigator: Orlando Bueno, MD AbbVie
  More Information

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02899052     History of Changes
Other Study ID Numbers: M15-538
First Submitted: September 1, 2016
First Posted: September 14, 2016
Last Update Posted: November 2, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AbbVie:
Refractory myeloma
Multiple Myeloma
Relapsed myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Venetoclax
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors