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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. Identifier: NCT03785184
Recruitment Status : Suspended (Safety)
First Posted : December 24, 2018
Last Update Posted : March 21, 2019
Genentech, Inc.
Celgene Corporation
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: venetoclax Drug: lenalidomide Drug: dexamethasone Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : April 29, 2019
Estimated Primary Completion Date : May 16, 2022
Estimated Study Completion Date : July 21, 2027

Arm Intervention/treatment
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).
Drug: venetoclax
tablet; oral
Other Name: ABT-199

Drug: lenalidomide
capsule; oral
Other Name: Revlimid

Drug: dexamethasone
tablet; oral

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. 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).

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03785184

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United States, California
Marin Cancer Care /ID# 208476
Greenbrae, California, United States, 94904
University of California, Los Angeles /ID# 208516
Los Angeles, California, United States, 90095
United States, Michigan
Karmanos Cancer Institute /ID# 208805
Detroit, Michigan, United States, 48201
Henry Ford Hospital /ID# 208481
Detroit, Michigan, United States, 48202
United States, North Carolina
Duke University Hospital /ID# 208306
Durham, North Carolina, United States, 27710
United States, Pennsylvania
UPMC Hillman Cancer Ctr /ID# 208121
Pittsburgh, Pennsylvania, United States, 15232
Australia, New South Wales
Westmead Hospital /ID# 210267
Westmead, New South Wales, Australia, 2145
Australia, South Australia
Flinders Centre for Innovation /ID# 210697
Adelaide, South Australia, Australia, 5042
Australia, Victoria
St. Vincents Hosp Melbourne /ID# 210266
Fitzroy, Victoria, Australia, 3065
Austin Hospital /ID# 210268
Heidelberg, Victoria, Australia, 3084
Monash Medical Centre /ID# 210269
Melbourne, Victoria, Australia, 3168
Canada, Alberta
Tom Baker Cancer Centre /ID# 208549
Calgary, Alberta, Canada, T2N 4N2
Canada, Ontario
Princess Margaret Cancer Centr /ID# 208923
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Hopital Maisonneuver-Rosemont /ID# 208550
Montreal, Quebec, Canada, H1T 2M4
McGill Univ HC /ID# 208486
Montreal, Quebec, Canada, H3G 1A4
Clinica Universitar de Navarra - Pamplona /ID# 209883
Pamplona, Navarra, Comunidad, Spain, 31008
Hospital Clinic de Barcelona /ID# 209888
Barcelona, Spain, 08036
Hspital Universitario Gregorio Maranon /ID# 209926
Madrid, Spain, 28009
Clinica Universitar de Navarra - Madrid /ID# 210131
Madrid, Spain, 28021
Hosp Univ 12 de Octubre /ID# 209887
Madrid, Spain, 28041
Hospital Univ Dr. Peset /ID# 209884
Valencia, Spain, 46017
Sponsors and Collaborators
Genentech, Inc.
Celgene Corporation
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Study Director: AbbVie Inc. AbbVie

Additional Information:
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Responsible Party: AbbVie Identifier: NCT03785184     History of Changes
Other Study ID Numbers: M16-104
First Posted: December 24, 2018    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.

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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

Keywords provided by AbbVie:
Multiple Myeloma
t(11;14)-Positive Multiple Myeloma

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents