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A Study of Venetoclax Plus Lenalidomide and Dexamethasone for the Treatment of Newly Diagnosed t(11;14)-Positive Multiple Myeloma in Subjects Who Are Ineligible for High-Dose Therapy

Primary Purpose

Multiple Myeloma

Status
Withdrawn
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
venetoclax
lenalidomide
dexamethasone
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Cancer, t(11;14)-Positive Multiple Myeloma, Venetoclax, Lenalidomide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Must have documented, confirmed active multiple myeloma (MM) with greater than or equal to 10% clonal bone marrow plasma cells or biopsy-proven bone or extramedullary plasmacytoma and any one or more of the following myeloma-defining events:

    • Evidence of end organ damage attributed to the underlying plasma cell proliferative disorder and satisfying at least one of the protocol specified laboratory criteria for calcium elevation, renal failure, anemia, or lytic bone lesions; OR
    • One or more of the biomarkers of malignancy as described in the protocol.
  • Must have MM positive for the t(11;14) translocation, as determined by methods described in the protocol.

  • Must have measurable disease defined by at least one of the following criteria:

    • Serum M-protein ≥ 1.0 g/dL (immunoglobulin [Ig]G myeloma) or greater than or equal to 0.5 g/dL (IgA, IgM, IgD, or IgE myeloma);
    • Urine M-protein greater than or equal to 200 mg/24 hours;
    • Serum free light chain (FLC) greater than or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal.
  • Newly diagnosed and not considered a candidate for high-dose therapy and hematopoietic stem cell transplantation (HSCT)
  • Must have Eastern Cooperative Oncology Group performance status less than or equal to 2.

Exclusion Criteria:

  • Has a co-existing condition as specified in the protocol.
  • Has history of other active malignancies, including myelodysplastic syndromes (MDS) within the past 3 years with specific exceptions detailed in the protocol.

  • Has been treated with or received any of the following:

    • Prior or current systemic therapy or hematopoietic stem cell transplantation (HSCT) for MM (a short course of treatment with corticosteroids equivalent to dexamethasone 40 mg/day for a maximum of 4 days is allowed before treatment); use of systemic strong or moderate inhibitor or inducer of cytochrome P450(CYP)3A within 7 days before the first dose of study drug.
    • Radiation therapy within 2 weeks of dosing
    • Plasmapheresis within 4 weeks of dosing
    • Immunization with live vaccine within 8 weeks of dosing
  • Has a contraindication or inability to comply with antithrombotic prophylaxis.

Sites / Locations

  • City of Hope /ID# 212211
  • Marin Cancer Care /ID# 208476
  • University of California, Los Angeles /ID# 208516
  • Karmanos Cancer Institute /ID# 208805
  • Henry Ford Hospital /ID# 208481
  • Duke University Hospital /ID# 208306
  • UPMC Hillman Cancer Ctr /ID# 208121
  • Westmead Hospital /ID# 210267
  • Flinders Centre for Innovation /ID# 210697
  • St. Vincents Hosp Melbourne /ID# 210266
  • Austin Hospital /ID# 210268
  • Monash Medical Centre /ID# 210269
  • Tom Baker Cancer Centre /ID# 208549
  • Princess Margaret Cancer Centr /ID# 208923
  • Hopital Maisonneuver-Rosemont /ID# 208550
  • McGill Univ HC /ID# 208486
  • Clinica Universitar de Navarra - Pamplona /ID# 209883
  • Hospital Clinic de Barcelona /ID# 209888
  • Hspital Universitario Gregorio Maranon /ID# 209926
  • Clinica Universitar de Navarra - Madrid /ID# 210131
  • Hosp Univ 12 de Octubre /ID# 209887
  • Hospital Univ Dr. Peset /ID# 209884

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Venetoclax + Lenalidomide + Dexamethasone

Arm Description

Venetoclax up to 800 mg orally every day (QD) QD on Days 1 - 28 plus lenalidomide up to 25 mg orally QD on Days 1 - 21 (28 day cycle) plus dexamethasone up to 40 mg orally once weekly (QW).

Outcomes

Primary Outcome Measures

Percentage of Participates Who Achieve CR
Complete response (CR) is defined as negative immunofixation of serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow.

Secondary Outcome Measures

Percent of Participants Who Achieve MRD Negativity
Minimal residual disease (MRD) negative after treatment is described as less than one myeloma cell per 100,000 bone marrow cells.
Percent of Participants Who Achieve VGPR or Better
Very Good Partial Response (VGPR) per international myeloma working group (IMWG) criteria is defined as serum or urine myeloma protein (m-protein) detectable by immunofixation but not on electrophoresis, or greater than or equal to 90% reduction in serum m-protein and urine m-protein less than 100 mg/24 hours.
Overall Response Rate (ORR)
ORR is described as the percentage of participants who experience partial response (PR) or better; PR per IMWG is described as follows: ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M protein by ≥ 90% or to < 200 mg/24 h If the serum and urine M-protein are not measurable, a decrease ≥ 50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, ≥ 50% reduction in bone marrow plasma cells is required in place of M-protein, provided baseline percentage was ≥ 30% In addition, if present at baseline, ≥ 50% reduction in size of soft tissue plasmacytomas is also required
Time to Response (TTR)
Time to response is defined as the time from randomization to the first response (CR, stringent complete response [sCR], VGPR, PR).
Duration of response (DOR)
DOR is defined as the time from first observation of PR to the time of disease progression, with deaths from causes other than progression censored.
Progression-free Survival (PFS)
PFS is defined as time from start of the treatment to disease progression or death (regardless of cause of death), whichever comes first.
Minimal Residual Disease (MRD) Negativity Rate at 12 Months
Percent of participants meeting the MRD Negative criteria at 12 months after initial dose; MRD Negative defined as less than one myeloma cell per 100,000 bone marrow cells.
Time to Disease Progression (TTP)
TTP is defined as the time from start of treatment to disease progression, with deaths from causes other than progression censored.
Time to Next Treatment (TTNT)
The time to next treatment is defined as the time between the date of the first study drug intake and the date of the first next treatment intake after study drug discontinuation.
Overall Survival (OS) Rate
OS was defined as the time from the date the participant was randomized to the date of death.

Full Information

First Posted
December 20, 2018
Last Updated
August 23, 2019
Sponsor
AbbVie
Collaborators
Genentech, Inc., Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT03785184
Brief Title
A Study of Venetoclax Plus Lenalidomide and Dexamethasone for the Treatment of Newly Diagnosed t(11;14)-Positive Multiple Myeloma in Subjects Who Are Ineligible for High-Dose Therapy
Official Title
A Phase 2, Multicenter, Single Arm, Open Label Study of Venetoclax Plus Lenalidomide and Dexamethasone for the Treatment of Newly Diagnosed t(11;14)-Positive Multiple Myeloma in Subjects Who Are Ineligible for High-Dose Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Withdrawn
Why Stopped
Strategic considerations
Study Start Date
April 29, 2019 (Anticipated)
Primary Completion Date
August 22, 2019 (Actual)
Study Completion Date
August 22, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
Genentech, Inc., Celgene Corporation

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 study will evaluate the safety and preliminary efficacy of venetoclax when combined with lenalidomide and dexamethasone for participants with newly diagnosed, active t(11;14) positive multiple myeloma (MM). This study will consist of 2 parts: Part 1 Dose Escalation and Part 2 Dose Expansion.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Cancer, t(11;14)-Positive Multiple Myeloma, Venetoclax, Lenalidomide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Venetoclax + Lenalidomide + Dexamethasone
Arm Type
Experimental
Arm Description
Venetoclax up to 800 mg orally every day (QD) QD on Days 1 - 28 plus lenalidomide up to 25 mg orally QD on Days 1 - 21 (28 day cycle) plus dexamethasone up to 40 mg orally once weekly (QW).
Intervention Type
Drug
Intervention Name(s)
venetoclax
Other Intervention Name(s)
ABT-199
Intervention Description
tablet; oral
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
capsule; oral
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Description
tablet; oral
Primary Outcome Measure Information:
Title
Percentage of Participates Who Achieve CR
Description
Complete response (CR) is defined as negative immunofixation of serum and urine, and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow.
Time Frame
From baseline up to approximately 24 months
Secondary Outcome Measure Information:
Title
Percent of Participants Who Achieve MRD Negativity
Description
Minimal residual disease (MRD) negative after treatment is described as less than one myeloma cell per 100,000 bone marrow cells.
Time Frame
From baseline up to approximately 24 months
Title
Percent of Participants Who Achieve VGPR or Better
Description
Very Good Partial Response (VGPR) per international myeloma working group (IMWG) criteria is defined as serum or urine myeloma protein (m-protein) detectable by immunofixation but not on electrophoresis, or greater than or equal to 90% reduction in serum m-protein and urine m-protein less than 100 mg/24 hours.
Time Frame
From baseline up to approximately 24 months
Title
Overall Response Rate (ORR)
Description
ORR is described as the percentage of participants who experience partial response (PR) or better; PR per IMWG is described as follows: ≥ 50% reduction of serum M-protein and reduction in 24-hour urinary M protein by ≥ 90% or to < 200 mg/24 h If the serum and urine M-protein are not measurable, a decrease ≥ 50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, ≥ 50% reduction in bone marrow plasma cells is required in place of M-protein, provided baseline percentage was ≥ 30% In addition, if present at baseline, ≥ 50% reduction in size of soft tissue plasmacytomas is also required
Time Frame
From baseline up to approximately 24 months
Title
Time to Response (TTR)
Description
Time to response is defined as the time from randomization to the first response (CR, stringent complete response [sCR], VGPR, PR).
Time Frame
From baseline up to approximately 24 months
Title
Duration of response (DOR)
Description
DOR is defined as the time from first observation of PR to the time of disease progression, with deaths from causes other than progression censored.
Time Frame
Approximately 7 years
Title
Progression-free Survival (PFS)
Description
PFS is defined as time from start of the treatment to disease progression or death (regardless of cause of death), whichever comes first.
Time Frame
Approximately 7 years
Title
Minimal Residual Disease (MRD) Negativity Rate at 12 Months
Description
Percent of participants meeting the MRD Negative criteria at 12 months after initial dose; MRD Negative defined as less than one myeloma cell per 100,000 bone marrow cells.
Time Frame
Approximately 12 months after initial dose of study drug
Title
Time to Disease Progression (TTP)
Description
TTP is defined as the time from start of treatment to disease progression, with deaths from causes other than progression censored.
Time Frame
Approximately 7 years
Title
Time to Next Treatment (TTNT)
Description
The time to next treatment is defined as the time between the date of the first study drug intake and the date of the first next treatment intake after study drug discontinuation.
Time Frame
Approximately 7 years
Title
Overall Survival (OS) Rate
Description
OS was defined as the time from the date the participant was randomized to the date of death.
Time Frame
Approximately 7 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Must have documented, confirmed active multiple myeloma (MM) with greater than or equal to 10% clonal bone marrow plasma cells or biopsy-proven bone or extramedullary plasmacytoma and any one or more of the following myeloma-defining events: Evidence of end organ damage attributed to the underlying plasma cell proliferative disorder and satisfying at least one of the protocol specified laboratory criteria for calcium elevation, renal failure, anemia, or lytic bone lesions; OR One or more of the biomarkers of malignancy as described in the protocol. Must have MM positive for the t(11;14) translocation, as determined by methods described in the protocol. Must have measurable disease defined by at least one of the following criteria: Serum M-protein ≥ 1.0 g/dL (immunoglobulin [Ig]G myeloma) or greater than or equal to 0.5 g/dL (IgA, IgM, IgD, or IgE myeloma); Urine M-protein greater than or equal to 200 mg/24 hours; Serum free light chain (FLC) greater than or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal. Newly diagnosed and not considered a candidate for high-dose therapy and hematopoietic stem cell transplantation (HSCT) Must have Eastern Cooperative Oncology Group performance status less than or equal to 2. Exclusion Criteria: Has a co-existing condition as specified in the protocol. Has history of other active malignancies, including myelodysplastic syndromes (MDS) within the past 3 years with specific exceptions detailed in the protocol. Has been treated with or received any of the following: Prior or current systemic therapy or hematopoietic stem cell transplantation (HSCT) for MM (a short course of treatment with corticosteroids equivalent to dexamethasone 40 mg/day for a maximum of 4 days is allowed before treatment); use of systemic strong or moderate inhibitor or inducer of cytochrome P450(CYP)3A within 7 days before the first dose of study drug. Radiation therapy within 2 weeks of dosing Plasmapheresis within 4 weeks of dosing Immunization with live vaccine within 8 weeks of dosing Has a contraindication or inability to comply with antithrombotic prophylaxis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope /ID# 212211
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Marin Cancer Care /ID# 208476
City
Greenbrae
State/Province
California
ZIP/Postal Code
94904
Country
United States
Facility Name
University of California, Los Angeles /ID# 208516
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Karmanos Cancer Institute /ID# 208805
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Henry Ford Hospital /ID# 208481
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Duke University Hospital /ID# 208306
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
UPMC Hillman Cancer Ctr /ID# 208121
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Westmead Hospital /ID# 210267
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Flinders Centre for Innovation /ID# 210697
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
Facility Name
St. Vincents Hosp Melbourne /ID# 210266
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Austin Hospital /ID# 210268
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Monash Medical Centre /ID# 210269
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Tom Baker Cancer Centre /ID# 208549
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Princess Margaret Cancer Centr /ID# 208923
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Hopital Maisonneuver-Rosemont /ID# 208550
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
McGill Univ HC /ID# 208486
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3G 1A4
Country
Canada
Facility Name
Clinica Universitar de Navarra - Pamplona /ID# 209883
City
Pamplona
State/Province
Navarra, Comunidad
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital Clinic de Barcelona /ID# 209888
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hspital Universitario Gregorio Maranon /ID# 209926
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Clinica Universitar de Navarra - Madrid /ID# 210131
City
Madrid
ZIP/Postal Code
28021
Country
Spain
Facility Name
Hosp Univ 12 de Octubre /ID# 209887
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Univ Dr. Peset /ID# 209884
City
Valencia
ZIP/Postal Code
46017
Country
Spain

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
Links:
URL
http://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 Plus Lenalidomide and Dexamethasone for the Treatment of Newly Diagnosed t(11;14)-Positive Multiple Myeloma in Subjects Who Are Ineligible for High-Dose Therapy

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