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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02899052
• Other study ID #: M15-538
• Secondary ID: 2019-004340-30
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 19, 2017
• Est. completion date: June 22, 2027

Study information

• Verified date: April 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: June 22, 2027
• Est. primary completion date: June 22, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Carfilzomib
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.
• Venetoclax
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
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.

Locations

Country	Name	City	State
Australia	Flinders Medical Centre /ID# 221345	Bedford, Park	South Australia
Australia	Border Medical Oncology Research Unit Albury Wodonga Regiona /ID# 222200	East Albury	New South Wales
Australia	Royal Hobart Hospital /ID# 217546	Hobart	Tasmania
Australia	Calvary Mater Newcastle /ID# 218739	Waratah	New South Wales
Hungary	Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 217625	Budapest
Hungary	Semmelweis Egyetem /ID# 217626	Budapest
Hungary	Debreceni Egyetem-Klinikai Kozpont /ID# 217624	Debrecen	Hajdu-Bihar
Hungary	Szegedi Tudományegyetem /ID# 219172	Szeged
Puerto Rico	Auxilio Mutuo Cancer Center /ID# 157853	San Juan
Puerto Rico	VA Caribbean Healthcare System /ID# 157854	San Juan
Spain	Hospital Universitario Germans Trias i Pujol /ID# 218006	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona /ID# 218007	Barcelona
Spain	Hospital General Universitario Gregorio Maranon /ID# 218005	Madrid
Spain	Hospital Universitario Ramon y Cajal /ID# 220925	Madrid
United States	Emory University, Winship Cancer Institute /ID# 161710	Atlanta	Georgia
United States	University of Maryland School of Medicine /ID# 159721	Baltimore	Maryland
United States	University of Alabama at Birmingham - Main /ID# 151405	Birmingham	Alabama
United States	The University of Chicago Medical Center /ID# 151395	Chicago	Illinois
United States	University of Texas Southwestern Medical Center /ID# 218336	Dallas	Texas
United States	Duke Cancer Center /ID# 162062	Durham	North Carolina
United States	Memorial Healthcare System /ID# 224862	Hollywood	Florida
United States	Indiana Blood & Marrow Transpl /ID# 218862	Indianapolis	Indiana
United States	Central Maine Medical Center /ID# 218856	Lewiston	Maine
United States	University of Kentucky Chandler Medical Center /ID# 151407	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences /ID# 151399	Little Rock	Arkansas
United States	University of Pennsylvania /ID# 151768	Philadelphia	Pennsylvania
United States	Washington University-School of Medicine /ID# 222651	Saint Louis	Missouri
United States	University of Utah /ID# 151397	Salt Lake City	Utah
United States	Duplicate_VA Puget Sound Healthcare Syst /ID# 155369	Seattle	Washington
United States	Oncology Hematology Associates (OHA) - Springfield /ID# 218855	Springfield	Missouri
United States	Baylor Scott & White Medical Center- Temple /ID# 218252	Temple	Texas
United States	Aurora Health Care, Aurora Cancer Center /ID# 209612	Wauwatosa	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Genentech, Inc; Onyx Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Hungary,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
Primary	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.	First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
Primary	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.	First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
Primary	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.	First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
Secondary	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	VGPR or better response rate is defined as the proportion of participants with documented VGPR or better based on IMWG criteria.	Up to approximately 17 months
Secondary	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.	Up to approximately 17 months
Secondary	Minimal residual disease (MRD)	MRD in the bone marrow by next generation sequencing.	Up to 2 years (Screening, Cycle 3 Day 1, and Confirmation of Stringent Complete Response [sCR]/Complete Response [CR])
Secondary	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.	Up to approximately 17 months
Secondary	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.	Up to approximately 17 months
Secondary	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.	Up to approximately 17 months
Secondary	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).	Up to approximately 17 months
Secondary	Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of Venetoclax	AUC0-24 post-dose of venetoclax.	Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
Secondary	Clearance (CL) of Carfilzomib	CL of carfilzomib.	Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary	Terminal Phase Elimination Rate Constant (ß) of Carfilzomib	ß of carfilzomib.	Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary	AUC from 0 to Infinity (AUC8) of Carfilzomib	AUC8 of carfilzomib.	Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary	AUC from Time 0 to the Time of the Last Measurable Concentration (AUCt) of Carfilzomib	AUCt of carfilzomib.	Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary	Maximum Plasma Concentration (Cmax) of Venetoclax	Cmax of venetoclax.	Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
Secondary	Cmax of Carfilzomib	Cmax of carfilzomib.	Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary	Terminal Elimination Half-life (t1/2) of Carfilzomib	t1/2 of carfilzomib.	Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary	Time to Maximum Plasma Concentration (Peak Time, Tmax) of Venetoclax	(Peak time, Tmax) of venetoclax.	Approximately 24 hours post-dose on Cycle 1 Days 1 and 15