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

Phase 2Active Not RecruitingNCT02899052

AbbVie120 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

120

Conditions

Multiple Myeloma

Interventions

CarfilzomibDRUG

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.

VenetoclaxDRUG

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

Dexamethasone

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (32)

Outcomes

Primary Outcomes

Number of Participants with Adverse Events

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.

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

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

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

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

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

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

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

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

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

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

Secondary Outcomes

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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.

University of Alabama at Birmingham - Main /ID# 151405

Birmingham, Alabama, United States

University of Arkansas for Medical Sciences /ID# 151399

Little Rock, Arkansas, United States

Memorial Healthcare System /ID# 224862

Hollywood, Florida, United States

Winship Cancer Institute of Emory University /ID# 161710

Atlanta, Georgia, United States

The University of Chicago Medical Center /ID# 151395

Chicago, Illinois, United States

Indiana Blood & Marrow Transpl /ID# 218862

Indianapolis, Indiana, United States

Duplicate_University of Kentucky Chandler Medical Center /ID# 151407

Lexington, Kentucky, United States

Central Maine Medical Center /ID# 218856

Lewiston, Maine, United States

Duplicate_University of Maryland School of Medicine /ID# 159721

Baltimore, Maryland, United States

Oncology Hematology Associates (OHA) - Springfield /ID# 218855

Springfield, Missouri, United States

...and 22 more locations

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

Time frame: Up to approximately 17 months

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

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 frame: Up to approximately 17 months

Minimal residual disease (MRD)

MRD in the bone marrow by next generation sequencing.

Time frame: Up to 2 years (Screening, Cycle 3 Day 1, and Confirmation of Stringent Complete Response [sCR]/Complete Response [CR])

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

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.

Time frame: Up to approximately 17 months

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

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.

Time frame: Up to approximately 17 months

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

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

Time frame: Up to approximately 17 months

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

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).

Time frame: Up to approximately 17 months

Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of Venetoclax

AUC0-24 post-dose of venetoclax.

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

Clearance (CL) of Carfilzomib

CL of carfilzomib.