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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02899052
Ethics application status
Date submitted
1/09/2016
Date registered
14/09/2016
Date last updated
23/11/2020

Titles & IDs
Public title
Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects 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 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.
Part 3: Further evaluation of the efficacy of the VenKd combination after completion of Part 1 and Part 2 in 60 additional subjects.


Treatment: Drugs: 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: 20 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

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

Outcomes
Primary outcome [1] 0 0
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
Objective Response Rate (ORR) of VenKd in participants with 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,
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
Very Good Partial Response (VGPR) or better response rate of VenKd in participants with relapsed or refractory MM (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.
Timepoint [3] 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 MM and in a subset of participants with high BCL-2 expression - VGPR or better response rate is defined as the proportion of participants with documented VGPR or better based on IMWG criteria.
Timepoint [1] 0 0
Up to approximately 17 months
Secondary outcome [2] 0 0
Progression-free survival (PFS) in participants with relapsed or refractory MM and in a subset of participants with high 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.
Timepoint [2] 0 0
Up to approximately 17 months
Secondary outcome [3] 0 0
Minimal residual disease (MRD) - MRD in the bone marrow by next generation sequencing.
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
Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of venetoclax
Timepoint [4] 0 0
Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [5] 0 0
Clearance (CL) of carfilzomib
Timepoint [5] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [6] 0 0
Duration of overall response (DOR) in participants with relapsed or refractory MM and in a subset of participants with high 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.
Timepoint [6] 0 0
Up to approximately 17 months
Secondary outcome [7] 0 0
Terminal phase elimination rate constant (ß) of carfilzomib
Timepoint [7] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [8] 0 0
AUC from 0 to infinity (AUC8)of carfilzomib
Timepoint [8] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [9] 0 0
Time to progression (TTP) in participants with relapsed or refractory MM and in a subset of participants with high 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.
Timepoint [9] 0 0
Up to approximately 17 months
Secondary outcome [10] 0 0
AUC from time 0 to the time of the last measurable concentration (AUCt) of carfilzomib
Timepoint [10] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [11] 0 0
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 - ORR is defined as the proportion of participants with documented partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria.
Timepoint [11] 0 0
Up to approximately 17 months
Secondary outcome [12] 0 0
Cmax of carfilzomib
Timepoint [12] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [13] 0 0
Terminal elimination half-life (t1/2) of carfilzomib
Timepoint [13] 0 0
Approximately 4 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [14] 0 0
Time to maximum plasma concentration (peak time, Tmax) of venetoclax
Timepoint [14] 0 0
Approximately 24 hours post-dose on Cycle 1 Days 1 and 15
Secondary outcome [15] 0 0
Maximum plasma concentration (Cmax) of venetoclax
Timepoint [15] 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.

- 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.

- For Part 3, Cohort 7, participants must meet the above criteria and also be positive
for translocation t(11;14) as determined by an analytically validated Fluorescent In
Situ Hybridization (FISH) assay per central laboratory testing.
Minimum age
18 Years
Maximum age
No limit
Gender
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

- 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 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,TAS
Recruitment hospital [1] 0 0
Border Medical Oncology /ID# 222200 - East Albury
Recruitment hospital [2] 0 0
Calvary Mater Newcastle /ID# 218739 - Waratah
Recruitment hospital [3] 0 0
Flinders Centre for Innovation /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
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Maine
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
United States of America
State/province [15] 0 0
Wisconsin
Country [16] 0 0
Hungary
State/province [16] 0 0
Budapest
Country [17] 0 0
Hungary
State/province [17] 0 0
Budapest VIII
Country [18] 0 0
Hungary
State/province [18] 0 0
Debrecen
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
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Onyx Therapeutics, Inc.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02899052
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
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
847.283.8955
Fax 0 0
Email 0 0
abbvieclinicaltrials@abbvie.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02899052