Clinical trial NCT02899052: Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma (MM)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Refractory myeloma
Relapsed myeloma
Relapsed or Refractory
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc; Onyx Therapeutics, Inc.
First posted: 2016-09-14
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.
* 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

Primary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
measure: 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
timeFrame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
measure: 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
timeFrame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
measure: 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
timeFrame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
Secondary outcomes:
measure: 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
timeFrame: Up to approximately 17 months
measure: 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
timeFrame: Up to approximately 17 months
measure: Minimal residual disease (MRD)
timeFrame: Up to 2 years (Screening, Cycle 3 Day 1, and Confirmation of Stringent Complete Response [sCR]/Complete Response [CR])
measure: 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
timeFrame: Up to approximately 17 months
measure: 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
timeFrame: Up to approximately 17 months
measure: 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
timeFrame: Up to approximately 17 months
measure: 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
timeFrame: Up to approximately 17 months
measure: Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of Venetoclax
timeFrame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
measure: Clearance (CL) of Carfilzomib
timeFrame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
measure: Terminal Phase Elimination Rate Constant (β) of Carfilzomib
timeFrame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
measure: AUC from 0 to Infinity (AUC∞) of Carfilzomib
timeFrame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
measure: AUC from Time 0 to the Time of the Last Measurable Concentration (AUCt) of Carfilzomib
timeFrame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
measure: Maximum Plasma Concentration (Cmax) of Venetoclax
timeFrame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
measure: Cmax of Carfilzomib
timeFrame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
measure: Terminal Elimination Half-life (t1/2) of Carfilzomib
timeFrame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
measure: Time to Maximum Plasma Concentration (Peak Time, Tmax) of Venetoclax
timeFrame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - Main /ID# 151405
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences /ID# 151399
state: Arkansas
city: Hollywood
country: United States
facility: Memorial Healthcare System /ID# 224862
state: Florida
city: Atlanta
country: United States
facility: Emory University, Winship Cancer Institute /ID# 161710
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medical Center /ID# 151395
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Blood & Marrow Transpl /ID# 218862
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center /ID# 151407
state: Kentucky
city: Lewiston
country: United States
facility: Central Maine Medical Center /ID# 218856
state: Maine
city: Baltimore
country: United States
facility: University of Maryland School of Medicine /ID# 159721
state: Maryland
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 222651
state: Missouri
city: Springfield
country: United States
facility: Oncology Hematology Associates (OHA) - Springfield /ID# 218855
state: Missouri
city: Durham
country: United States
facility: Duke Cancer Center /ID# 162062
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania /ID# 151768
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center /ID# 218336
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Medical Center- Temple /ID# 218252
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah /ID# 151397
state: Utah
city: Seattle
country: United States
facility: Duplicate_VA Puget Sound Healthcare Syst /ID# 155369
state: Washington
city: Wauwatosa
country: United States
facility: Aurora Health Care, Aurora Cancer Center /ID# 209612
state: Wisconsin
city: East Albury
country: Australia
facility: Border Medical Oncology Research Unit Albury Wodonga Regiona /ID# 222200
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle /ID# 218739
state: New South Wales
city: Bedford, Park
country: Australia
facility: Flinders Medical Centre /ID# 221345
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital /ID# 217546
state: Tasmania
city: Debrecen
country: Hungary
facility: Debreceni Egyetem-Klinikai Kozpont /ID# 217624
state: Hajdu-Bihar
city: Budapest
country: Hungary
facility: Semmelweis Egyetem /ID# 217626
city: Budapest
country: Hungary
facility: Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 217625
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem /ID# 219172
city: San Juan
country: Puerto Rico
facility: Auxilio Mutuo Cancer Center /ID# 157853
city: San Juan
country: Puerto Rico
facility: VA Caribbean Healthcare System /ID# 157854
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol /ID# 218006
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona /ID# 218007
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon /ID# 218005
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal /ID# 220925
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: Costa LJ, Davies FE, Monohan GP, Kovacsovics T, Burwick N, Jakubowiak A, Kaufman JL, Hong WJ, Dail M, Salem AH, Yang X, Masud AA, Munasinghe W, Ross JA, Bueno OF, Kumar SK, Stadtmauer EA. Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma. Blood Adv. 2021 Oct 12;5(19):3748-3759. doi: 10.1182/bloodadvances.2020004146.