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A Study Evaluating Venetoclax (ABT-199) in Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Standard Therapy

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ClinicalTrials.gov Identifier: NCT02755597
Recruitment Status : Suspended (Safety)
First Posted : April 29, 2016
Last Update Posted : March 21, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

Brief Summary:
This is a Phase 3, multicenter, randomized, double blind, placebo-controlled study evaluating the efficacy and safety of venetoclax plus bortezomib and dexamethasone in subjects with relapsed or refractory multiple myeloma who are considered sensitive or naïve to proteasome inhibitors and received 1 to 3 prior lines of therapy for multiple myeloma.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Multiple Myeloma Drug: Placebo Drug: Bortezomib Drug: Dexamethasone Drug: Venetoclax Phase 3

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)
Actual Enrollment : 291 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double Blind Study of Bortezomib and Dexamethasone in Combination With Either Venetoclax or Placebo in Subjects With Relapsed or Refractory Multiple Myeloma Who Are Sensitive or Naïve to Proteasome Inhibitors
Actual Study Start Date : July 12, 2016
Estimated Primary Completion Date : September 2, 2019
Estimated Study Completion Date : February 15, 2022


Arm Intervention/treatment
Placebo Comparator: Placebo + Bortezomib and Dexamethasone
Cycles 1-8: Placebo (to match venetoclax 100mg tablet) 800mg orally every day (QD) on days 1 - 21 plus bortezomib 1.3mg/m2 on days 1,4,8 & 11 and dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 Cycles 9 and beyond: Placebo (to match venetoclax 100mg tablet) 800mg orally every day (QD) on days 1 - 35 plus bortezomib 1.3mg/m2 on days 1, 8, 15 and 22 and dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16, 22 and 23
Drug: Placebo
Tablet

Drug: Bortezomib
Solution for subcutaneous injection

Drug: Dexamethasone
Tablet

Experimental: Venetoclax + Bortezomib and Dexamethasone
Cycles 1-8: Venetoclax 800mg orally every day (QD) on days 1 - 21 plus bortezomib 1.3mg/m2 on days 1,4,8 & 11 and dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 Cycles 9 and beyond: Venetoclax 800mg orally every day (QD) on days 1 - 35 plus bortezomib 1.3mg/m2 on days 1, 8, 15 and 22 and dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16, 22 and 23
Drug: Bortezomib
Solution for subcutaneous injection

Drug: Dexamethasone
Tablet

Drug: Venetoclax
Tablet
Other Name: ABT-199




Primary Outcome Measures :
  1. Progression-free survival (PFS). [ Time Frame: Measured at subject's baseline (prior to subject's first dose) and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Collect International Myeloma Working Group (IMWG) disease assessments at Cycle 1 Day 1 (C1D1) of each cycle or to confirm disease progression.


Secondary Outcome Measures :
  1. Brief Pain Inventory - Short Form [BPI-SF] - Worst Pain [ Time Frame: Starting with Cycle 1 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days), collect on Day 1 of every other cycle and the Treatment Completion Visit (TCV) while participant is on treatment (approximately 2 years). ]
  2. Duration of Response (DOR). [ Time Frame: Measured at subject's initial response and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Collect International Myeloma Working Group (IMWG) disease assessments at C1D1 of each cycle or to confirm disease progression.

  3. Progression-Free Survival (PFS) in subjects with high B-cell lymphoma 2 (BCL-2) expression. [ Time Frame: Measured at subject's baseline (prior to subject's first dose) and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Bone marrow aspirate and bone marrow core biopsy tissue will be evaluated with the goal of defining the relationship between BCL-2 expression and disease status.

  4. Minimal Residual Disease (MRD) status. [ Time Frame: Measured from baseline up to the time of suspected CR/stringent complete response (sCR) with an expected average of 6 months. ]
    MRD status will be assessed using Next Generation Sequencing.

  5. Objective Response Rate (ORR). [ Time Frame: Measured at subject's baseline (prior to subject's first dose) and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Collect International Myeloma Working Group (IMWG) disease assessments at C1D1 of each cycle or to confirm disease progression.

  6. Patient Reported Outcomes Measurement Information System - (PROMIS) [ Time Frame: Starting with Cycle 1 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days), collect on Day 1 of every other cycle and the Treatment Completion Visit (TCV) while participant is on treatment (approximately 2 years). ]
  7. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) - Physical Functioning [ Time Frame: Starting with Cycle 1 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days), collect on Day 1 of every other cycle and the Treatment Completion Visit (TCV) while participant is on treatment (approximately 2 years). ]
  8. Overall survival (OS). [ Time Frame: Measured up to 6 years after the first subject is randomized. ]
    Measured from the date of the last dose and continuing either until the endpoint of death, until the subject is lost to follow-up, subject withdraws consent, or until study termination by AbbVie, whichever occurs first.

  9. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30) - Global Health Status [ Time Frame: Starting with Cycle 1 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days), collect on Day 1 of every other cycle and the Treatment Completion Visit (TCV) while participant is on treatment (approximately 2 years). ]
  10. Very Good Partial Response (VGPR) or better response rate. [ Time Frame: Measured at subject's baseline (prior to subject's first dose) and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Collect International Myeloma Working Group (IMWG) disease assessments at C1D1 of each cycle or to confirm disease progression.

  11. Time to disease progression (TTP). [ Time Frame: Measured at subject's baseline (prior to subject's first dose) and at Day 1 of every Cycle thereafter for up to 3 years following the last subject first dose. ]
    Collect International Myeloma Working Group (IMWG) disease assessments at C1D1 of each cycle or to confirm disease progression.



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 to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 2
  • Participant has documented relapsed or progressive multiple myeloma on or after any regimen or who are refractory to the most recent line of therapy. Relapsed myeloma is defined as previously treated myeloma that progresses and requires initiation of salvage therapy, but does not meet the criteria for refractory myeloma. Refractory myeloma is defined as disease that is non responsive (failure to achieve minimal response or development of progressive disease [PD]) while on primary or salvage therapy, or progresses within 60 days of last therapy.
  • Participant must have received prior treatment with at least one, but no more than three, prior lines of therapy for multiple myeloma. A line of therapy consists of greater than or equal to 1 complete cycle of a single agent, a regimen consisting of combination of several drugs, or a planned sequential therapy of various regimens.
  • Prior treatment with bortezomib or other proteasome inhibitor is allowed, provided ALL of the following criteria are met: Disease is NOT refractory to any proteasome inhibitor, defined as no disease progression (i.e., PD, per IMWG or European Society for Blood and Marrow Transplantation [EBMT] criteria) while receiving proteasome inhibitor therapy or within 60 days after the last dose, AND best response achieved with any proteasome inhibitor therapy (alone or in combination) was at least a PR, AND participant did not discontinue any proteasome inhibitor due to intolerance or greater than or equal to Grade 3 related toxicity.
  • Participant has measurable disease at Screening, defined as at least one of the following: Serum M-protein greater than or equal to 0.5 g/dL, OR Urine M-protein greater than or equal to 200 mg in 24-hours, OR serum immunoglobulin free light chain (FLC) greater than or equal to 10 mg/dL provided serum FLC ratio is abnormal.

Exclusion Criteria:

  • Participant is refractory to any proteasome inhibitor, defined as progression on or within 60 days of the last dose of a proteasome inhibitor-containing regimen.
  • Participant has had prior treatment with proteasome inhibitor within 60 days prior to first dose of study drug.
  • Participant has any of the following conditions:

Non-secretory or oligo-secretory multiple myeloma, active plasma cell leukemia i.e., either 20% of peripheral white blood cells or greater than 2.0 X 10^9/liter (L) circulating plasma cells by standard differential, waldenstrom's macroglobulinemia, amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), known Human Immunodeficiency Viral (HIV) infection, active hepatitis B or C infection based on blood screen tests, significant cardiovascular disease, including uncontrolled angina, severe or uncontrolled arrhythmia, recent myocardial infarction within 6 months of randomization, or congestive heart failure New York Heart Association (NYHA) Class greater than or equal to 3, Major surgery within 4 weeks prior to randomization, acute infections requiring parenteral therapy (antibiotic, antifungal, or antiviral) within 14 days prior to randomization, peripheral neuropathy greater than or equal to Grade 3 or greater than or equal to Grade 2 with pain within 2 weeks prior to randomization, uncontrolled diabetes or uncontrolled hypertension within 14 days prior to randomization, any other medical condition that, in the opinion of the Investigator, would adversely affect the participant's participation in the study

  • Participant has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions: Adequately treated in situ carcinoma of the cervix uteri or the breast, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment, previous malignancy with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study
  • If participant had prior allogeneic stem cell transplant (SCT), participant has evidence of ongoing graft-versus-host disease (GvHD).

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 ClinicalTrials.gov identifier (NCT number): NCT02755597


  Show 97 Study Locations
Sponsors and Collaborators
AbbVie
Genentech, Inc.
Investigators
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Study Director: AbbVie Inc. AbbVie

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02755597     History of Changes
Other Study ID Numbers: M14-031
2015-004411-20 ( EudraCT Number )
First Posted: April 29, 2016    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.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

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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:
relapsed/refractory multiple myeloma
relapsed multiple myeloma
refractory multiple myeloma
multiple myeloma

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