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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: venetoclax; Drug: lenalidomide; Drug: dexamethasone

• Study Type: Interventional
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital /ID# 210267
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Centre for Innovation /ID# 210697
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincents Hosp Melbourne /ID# 210266
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital /ID# 210268
    • Melbourne, Victoria, Australia, 3168
      • Monash Medical Centre /ID# 210269
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre /ID# 208549
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centr /ID# 208923
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuver-Rosemont /ID# 208550
    • Montreal, Quebec, Canada, H3G 1A4
      • McGill Univ HC /ID# 208486
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona /ID# 209888
  • Madrid, Spain, 28009
    • Hspital Universitario Gregorio Maranon /ID# 209926
  • Madrid, Spain, 28021
    • Clinica Universitar de Navarra - Madrid /ID# 210131
  • Madrid, Spain, 28041
    • Hosp Univ 12 de Octubre /ID# 209887
  • Valencia, Spain, 46017
    • Hospital Univ Dr. Peset /ID# 209884
  • Navarra, Comunidad
    • Pamplona, Navarra, Comunidad, Spain, 31008
      • Clinica Universitar de Navarra - Pamplona /ID# 209883
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope /ID# 212211
    • Greenbrae, California, United States, 94904
      • Marin Cancer Care /ID# 208476
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles /ID# 208516
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute /ID# 208805
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital /ID# 208481
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital /ID# 208306
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Ctr /ID# 208121

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: ABT-199; Drug: lenalidomide; capsule; oral; Other Names: Revlimid; Drug: dexamethasone; tablet; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From baseline up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From baseline up to approximately 24 months
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.	From baseline up to approximately 24 months
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	From baseline up to approximately 24 months
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).	From baseline up to approximately 24 months
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.	Approximately 7 years
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.	Approximately 7 years
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.	Approximately 12 months after initial dose of study drug
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.	Approximately 7 years
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.	Approximately 7 years
Overall Survival (OS) Rate	OS was defined as the time from the date the participant was randomized to the date of death.	Approximately 7 years

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Genentech, Inc.; Celgene Corporation

Publications and helpful links

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 29, 2019
• Primary Completion (Actual): August 22, 2019
• Study Completion (Actual): August 22, 2019

Study Registration Dates

• First Submitted: December 20, 2018
• First Submitted That Met QC Criteria: December 20, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 23, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Cancer; Multiple Myeloma; Lenalidomide; Venetoclax; t(11;14)-Positive Multiple Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide; Venetoclax
• Other Study ID Numbers: M16-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• 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