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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02899052




Registration number
NCT02899052
Ethics application status
Date submitted
1/09/2016
Date registered
14/09/2016

Titles & IDs
Public title
Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma (MM)
Scientific 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
Secondary ID [1] 0 0
2019-004340-30
Secondary ID [2] 0 0
M15-538
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Carfilzomib
Treatment: Drugs - Venetoclax
Treatment: Drugs - Dexamethasone

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 18 participants. 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 additional participants. Participants may discontinue Kd but may continue receiving venetoclax once daily (QD) as monotherapy.

Part 3: Further evaluation of the efficacy of the VenKd combination after completion of Part 1 and Part 2 in 7 additional participants.

Part 4, An additional 65 participants t(11;14) positive will receive varying doses of the VenKd combination or carfilzomib and dexamethasone


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Adverse Events
Timepoint [1] 0 0
First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
Primary outcome [3] 0 0
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
Timepoint [3] 0 0
First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
Primary outcome [4] 0 0
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
Timepoint [4] 0 0
First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Up to approximately 17 months
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Up to approximately 17 months
Secondary outcome [3] 0 0
Minimal residual disease (MRD)
Timepoint [3] 0 0
Up to 2 years (Screening, Cycle 3 Day 1, and Confirmation of Stringent Complete Response [sCR]/Complete Response [CR])
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Up to approximately 17 months
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Up to approximately 17 months
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Up to approximately 17 months
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Up to approximately 17 months
Secondary outcome [8] 0 0
Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of Venetoclax
Timepoint [8] 0 0
Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [9] 0 0
Clearance (CL) of Carfilzomib
Timepoint [9] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [10] 0 0
Terminal Phase Elimination Rate Constant (ß) of Carfilzomib
Timepoint [10] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [11] 0 0
AUC from 0 to Infinity (AUC8) of Carfilzomib
Timepoint [11] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [12] 0 0
AUC from Time 0 to the Time of the Last Measurable Concentration (AUCt) of Carfilzomib
Timepoint [12] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [13] 0 0
Maximum Plasma Concentration (Cmax) of Venetoclax
Timepoint [13] 0 0
Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [14] 0 0
Cmax of Carfilzomib
Timepoint [14] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [15] 0 0
Terminal Elimination Half-life (t1/2) of Carfilzomib
Timepoint [15] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [16] 0 0
Time to Maximum Plasma Concentration (Peak Time, Tmax) of Venetoclax
Timepoint [16] 0 0
Approximately 24 hours post-dose on Cycle 1 Days 1 and 15

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
22/06/2027
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,TAS
Recruitment hospital [1] 0 0
Border Medical Oncology Research Unit Albury Wodonga Regiona /ID# 222200 - East Albury
Recruitment hospital [2] 0 0
Calvary Mater Newcastle /ID# 218739 - Waratah
Recruitment hospital [3] 0 0
Flinders Medical Centre /ID# 221345 - Bedford, Park
Recruitment hospital [4] 0 0
Royal Hobart Hospital /ID# 217546 - Hobart
Recruitment postcode(s) [1] 0 0
2640 - East Albury
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
5042 - Bedford, Park
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Maine
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Hungary
State/province [17] 0 0
Hajdu-Bihar
Country [18] 0 0
Hungary
State/province [18] 0 0
Budapest
Country [19] 0 0
Hungary
State/province [19] 0 0
Szeged
Country [20] 0 0
Puerto Rico
State/province [20] 0 0
San Juan
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Genentech, Inc; Onyx Therapeutics, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
Available to whom?
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/abbvie/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02899052