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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03785184
Recruitment Status : Withdrawn (Strategic considerations)
First Posted : December 24, 2018
Last Update Posted : August 27, 2019
Sponsor:
Collaborators:
Genentech, Inc.
Celgene Corporation
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE December 20, 2018
First Posted Date  ICMJE December 24, 2018
Last Update Posted Date August 27, 2019
Estimated Study Start Date  ICMJE April 29, 2019
Actual Primary Completion Date August 22, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2018)
Percentage of Participates Who Achieve CR [ Time Frame: From baseline up to approximately 24 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03785184 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2018)
  • Percent of Participants Who Achieve MRD Negativity [ Time Frame: From baseline up to approximately 24 months ]
    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 [ Time Frame: From baseline up to approximately 24 months ]
    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) [ Time Frame: From baseline up to approximately 24 months ]
    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 Frame: From baseline up to approximately 24 months ]
    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) [ Time Frame: Approximately 7 years ]
    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) [ Time Frame: Approximately 7 years ]
    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 [ Time Frame: Approximately 12 months after initial dose of study drug ]
    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) [ Time Frame: Approximately 7 years ]
    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) [ Time Frame: Approximately 7 years ]
    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 [ Time Frame: Approximately 7 years ]
    OS was defined as the time from the date the participant was randomized to the date of death.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: venetoclax
    tablet; oral
    Other Name: ABT-199
  • Drug: lenalidomide
    capsule; oral
    Other Name: Revlimid
  • Drug: dexamethasone
    tablet; oral
Study Arms  ICMJE Experimental: Venetoclax + Lenalidomide + Dexamethasone
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).
Interventions:
  • Drug: venetoclax
  • Drug: lenalidomide
  • Drug: dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 23, 2019)
0
Original Estimated Enrollment  ICMJE
 (submitted: December 20, 2018)
40
Actual Study Completion Date  ICMJE August 22, 2019
Actual Primary Completion Date August 22, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03785184
Other Study ID Numbers  ICMJE M16-104
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
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.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE
  • Genentech, Inc.
  • Celgene Corporation
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP