Back to resultsA Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Venetoclax
Pomalidomide
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Cancer, Multiple Myeloma (MM), Relapsed or Refractory (R/R), Venetoclax, Pomalidomide, Dexamethasone
Eligibility Criteria
Inclusion Criteria:
- Relapsed or refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen
- Measurable disease as described in the protocol
- Received at least 1 prior line of therapy as described in the protocol
- Must meet prior antimyeloma treatment parameters, as described in the protocol, and includes:
- Received at least 2 consecutive cycles of lenalidomide or a lenalidomide-containing regimen
- Refractory to lenalidomide
- Exposed to a proteasome inhibitor (PI) alone or in combination with another agent
- Had a response of partial response (PR) or better to prior therapy based on the investigator's determination of response as defined by International Myeloma Working Group (IMWG) criteria
- Has t(11;14) status as described in the protocol and meets the following criteria:
- For Part 1: MM participants independent of cytogenetic profile
- For Part 2, Arm A: participant must be t(11;14) positive
- For Part 2, Arm B: participant must be t(11;14) negative
- An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Adequate kidney, liver and hematologic laboratory values
Exclusion Criteria:
- Previous treatment with venetoclax or other BCL-2 inhibitors, or previous treatment with pomalidomide
- Known sensitivity to any IMiDs
- Allogenic or syngeneic stem cell transplant within 6 months before the first dose of study drug or active ongoing graft versus host disease
- Autologous stem cell transplant within 12 weeks before the first dose of study drug
- Known meningeal involvement of MM
Sites / Locations
- John B. Amos Cancer Center - C /ID# 202055
- University of Kansas Cancer Center /ID# 201292
- Washington University-School of Medicine /ID# 201287
- Duke University Hospital /ID# 200805
- Ohio State Cancer Center /ID# 202443
- Hospital Universitario Germans Trias i Pujol /ID# 200959
- Hospital Universitario Vall d'Hebron /ID# 200967
- Hospital Clinico Universitario de Salamanca /ID# 200958
- Leicester Royal Infirmary /ID# 202238
- Norfolk and Norwich Univ Hosp /ID# 202240
- Univ Hospitals Birmingham NHS Foundation trust /ID# 203188
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part 1: Dose Escalation
Part 2: Dose Expansion, t(11;14) positive
Part 2: Dose Expansion, t(11;14) negative
Arm Description
Venetoclax (400 mg oral [PO], once daily [QD]) administered with pomalidomide (4 mg PO, QD) and dexamethasone (40 mg once weekly [qw]) in 28-day cycles until documented disease progression, documented unacceptable toxicity, withdrawal of consent, or the participant met other criteria for discontinuation per study protocol
Participants positive for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral [PO], once daily [QD]) and dexamethasone (40 mg once weekly [qw])
Participants negative for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral [PO], once daily [QD]) and dexamethasone (40 mg once weekly [qw])
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.
Overall Response Rate (ORR)
ORR is defined as the percentage of participants experiencing a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) using the International Myeloma Working Group (IMWG) 2016 criteria for disease response and progression. CR= negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow; sCR= CR + normal serum free light chain (FLC) ratio and absence of clonal cells in bone marrow; VGPR= serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein level + urine M-protein level < 100 mg per 24 hours; PR= ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours.
Secondary Outcome Measures
Progression-Free Survival (PFS)
PFS is defined as the number of days from the date of first dose of any study drug to the date of disease progression or death, whichever occurs first. All disease progression was to be included regardless of whether the event occurred during or after the participant was taking any study drug.
Duration of Response (DOR)
DOR for a given participant is defined as the number of days from the date of that participant's first documented response (Partial Response [PR] or better) to the date of first documented disease progression (PD) or death due to multiple myeloma (MM), whichever occurs first. If the participant with a documented response did not have an event of PD and the participant had not died due to MM, the participant's data was to be censored.
Time-to-progression (TTP)
TTP for a given participant is defined as the number of days from the date of first dose to the date of first documented disease progression (PD) or death due to multiple myeloma (MM), whichever occurs first. If the participant did not have an event of PD and the participant had not died due to MM, the participant's data was to be censored.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03567616
Brief Title
A Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma
Official Title
A Phase 2, Open-Label, Multicenter, Dose-Escalation and Expansion Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
Following results of the primary progression-free survival analysis from Study NCT02755597, company-sponsored MM studies were placed on partial clinical hold (PCH). Sponsor did not pursue release of the PCH for this study.
Study Start Date
October 18, 2018 (Actual)
Primary Completion Date
June 18, 2020 (Actual)
Study Completion Date
June 18, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
Celgene
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This was an open-label, multicenter study designed to evaluate the safety and preliminary efficacy of venetoclax combined with pomalidomide and dexamethasone in participants with relapsed or refractory (R/R) multiple myeloma (MM) who received at least 1 prior line of therapy with documented evidence of progression during or after the participant's last treatment regimen. The study was designed to consist of 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). For Part 2 the participants were to be divided into 2 cohorts, participants positive for t(11;14) translocation and participants negative for t(11;14) translocation.
Detailed Description
Following communication of the results of the primary progression-free survival (PFS) analysis from the Phase 3 BELLINI study (Study M14-031; NCT02755597), the company-sponsored MM studies were placed on partial clinical hold (PCH) in March 2019 by the United States (US) Food and Drug Administration and enrollment was halted. The sponsor did not pursue release of the PCH for this study; therefore, enrollment was not re-opened. In accordance with the terms of the PCH, participants who were deriving clinical benefit were allowed to continue to receive treatment. One participant was still active in Part 1 of the study when the sponsor decided not to pursue release of the PCH (in January 2020) and, therefore, continued to receive treatment and have regular assessments until disease progression. The study was discontinued when the last participant completed study treatment. No participants were enrolled in Part 2 of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Cancer, Multiple Myeloma (MM), Relapsed or Refractory (R/R), Venetoclax, Pomalidomide, Dexamethasone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1: Dose Escalation
Arm Type
Experimental
Arm Description
Venetoclax (400 mg oral [PO], once daily [QD]) administered with pomalidomide (4 mg PO, QD) and dexamethasone (40 mg once weekly [qw]) in 28-day cycles until documented disease progression, documented unacceptable toxicity, withdrawal of consent, or the participant met other criteria for discontinuation per study protocol
Arm Title
Part 2: Dose Expansion, t(11;14) positive
Arm Type
Experimental
Arm Description
Participants positive for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral [PO], once daily [QD]) and dexamethasone (40 mg once weekly [qw])
Arm Title
Part 2: Dose Expansion, t(11;14) negative
Arm Type
Experimental
Arm Description
Participants negative for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral [PO], once daily [QD]) and dexamethasone (40 mg once weekly [qw])
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-199, GDC-0199, Venclexta
Intervention Description
Tablet; oral
Intervention Type
Drug
Intervention Name(s)
Pomalidomide
Other Intervention Name(s)
Pomalyst
Intervention Description
Capsule; oral
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Administered orally; for participants over 75 years of age, dexamethasone could have been administered at a 20 mg dose [qw]
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.
Time Frame
From first dose of study drug until 30 days following last dose of study drug (up to 70 weeks)
Title
Overall Response Rate (ORR)
Description
ORR is defined as the percentage of participants experiencing a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) using the International Myeloma Working Group (IMWG) 2016 criteria for disease response and progression. CR= negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow; sCR= CR + normal serum free light chain (FLC) ratio and absence of clonal cells in bone marrow; VGPR= serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein level + urine M-protein level < 100 mg per 24 hours; PR= ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours.
Time Frame
Approximately 15 months
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
PFS is defined as the number of days from the date of first dose of any study drug to the date of disease progression or death, whichever occurs first. All disease progression was to be included regardless of whether the event occurred during or after the participant was taking any study drug.
Time Frame
Approximately 20 months
Title
Duration of Response (DOR)
Description
DOR for a given participant is defined as the number of days from the date of that participant's first documented response (Partial Response [PR] or better) to the date of first documented disease progression (PD) or death due to multiple myeloma (MM), whichever occurs first. If the participant with a documented response did not have an event of PD and the participant had not died due to MM, the participant's data was to be censored.
Time Frame
Approximately 15 months
Title
Time-to-progression (TTP)
Description
TTP for a given participant is defined as the number of days from the date of first dose to the date of first documented disease progression (PD) or death due to multiple myeloma (MM), whichever occurs first. If the participant did not have an event of PD and the participant had not died due to MM, the participant's data was to be censored.
Time Frame
Approximately 15 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Relapsed or refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen
Measurable disease as described in the protocol
Received at least 1 prior line of therapy as described in the protocol
Must meet prior antimyeloma treatment parameters, as described in the protocol, and includes:
Received at least 2 consecutive cycles of lenalidomide or a lenalidomide-containing regimen
Refractory to lenalidomide
Exposed to a proteasome inhibitor (PI) alone or in combination with another agent
Had a response of partial response (PR) or better to prior therapy based on the investigator's determination of response as defined by International Myeloma Working Group (IMWG) criteria
Has t(11;14) status as described in the protocol and meets the following criteria:
For Part 1: MM participants independent of cytogenetic profile
For Part 2, Arm A: participant must be t(11;14) positive
For Part 2, Arm B: participant must be t(11;14) negative
An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Adequate kidney, liver and hematologic laboratory values
Exclusion Criteria:
Previous treatment with venetoclax or other BCL-2 inhibitors, or previous treatment with pomalidomide
Known sensitivity to any IMiDs
Allogenic or syngeneic stem cell transplant within 6 months before the first dose of study drug or active ongoing graft versus host disease
Autologous stem cell transplant within 12 weeks before the first dose of study drug
Known meningeal involvement of MM
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
John B. Amos Cancer Center - C /ID# 202055
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904
Country
United States
Facility Name
University of Kansas Cancer Center /ID# 201292
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205-2528
Country
United States
Facility Name
Washington University-School of Medicine /ID# 201287
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Duke University Hospital /ID# 200805
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Ohio State Cancer Center /ID# 202443
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Hospital Universitario Germans Trias i Pujol /ID# 200959
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Universitario Vall d'Hebron /ID# 200967
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinico Universitario de Salamanca /ID# 200958
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Leicester Royal Infirmary /ID# 202238
City
Leicester
State/Province
England
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Facility Name
Norfolk and Norwich Univ Hosp /ID# 202240
City
Norwich
State/Province
Norfolk
ZIP/Postal Code
NR4 7UY
Country
United Kingdom
Facility Name
Univ Hospitals Birmingham NHS Foundation trust /ID# 203188
City
Birmingham
ZIP/Postal Code
B15 2TG
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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 and 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.
IPD Sharing Time Frame
Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
IPD Sharing Access Criteria
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 (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
IPD Sharing URL
https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Citations:
PubMed Identifier
34551886
Citation
Gasparetto C, Bowles KM, Abdallah AO, Morris L, Mander G, Coppola S, Wang J, Ross JA, Bueno OF, Arriola E, Mateos MV. A Phase II Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2021 Nov;21(11):775-784. doi: 10.1016/j.clml.2021.07.029. Epub 2021 Aug 1.
Results Reference
derived
Links:
URL
https://www.rxabbvie.com/
Description
This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.
Learn more about this trial
A Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma
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