Clinical trial NCT03785184: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Cancer
t(11;14)-Positive Multiple Myeloma
Venetoclax
Lenalidomide
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
name: Celgene Corporation
First posted: 2018-12-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participates Who Achieve CR
timeFrame: From baseline up to approximately 24 months
Secondary outcomes:
measure: Percent of Participants Who Achieve MRD Negativity
timeFrame: From baseline up to approximately 24 months
measure: Percent of Participants Who Achieve VGPR or Better
timeFrame: From baseline up to approximately 24 months
measure: Overall Response Rate (ORR)
timeFrame: From baseline up to approximately 24 months
measure: Time to Response (TTR)
timeFrame: From baseline up to approximately 24 months
measure: Duration of response (DOR)
timeFrame: Approximately 7 years
measure: Progression-free Survival (PFS)
timeFrame: Approximately 7 years
measure: Minimal Residual Disease (MRD) Negativity Rate at 12 Months
timeFrame: Approximately 12 months after initial dose of study drug
measure: Time to Disease Progression (TTP)
timeFrame: Approximately 7 years
measure: Time to Next Treatment (TTNT)
timeFrame: Approximately 7 years
measure: Overall Survival (OS) Rate
timeFrame: Approximately 7 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope /ID# 212211
state: California
city: Greenbrae
country: United States
facility: Marin Cancer Care /ID# 208476
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles /ID# 208516
state: California
city: Detroit
country: United States
facility: Karmanos Cancer Institute /ID# 208805
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital /ID# 208481
state: Michigan
city: Durham
country: United States
facility: Duke University Hospital /ID# 208306
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Ctr /ID# 208121
state: Pennsylvania
city: Westmead
country: Australia
facility: Westmead Hospital /ID# 210267
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Centre for Innovation /ID# 210697
state: South Australia
city: Fitzroy
country: Australia
facility: St. Vincents Hosp Melbourne /ID# 210266
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital /ID# 210268
state: Victoria
city: Melbourne
country: Australia
facility: Monash Medical Centre /ID# 210269
state: Victoria
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre /ID# 208549
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centr /ID# 208923
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuver-Rosemont /ID# 208550
state: Quebec
city: Montreal
country: Canada
facility: McGill Univ HC /ID# 208486
state: Quebec
city: Pamplona
country: Spain
facility: Clinica Universitar de Navarra - Pamplona /ID# 209883
state: Navarra, Comunidad
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona /ID# 209888
city: Madrid
country: Spain
facility: Hspital Universitario Gregorio Maranon /ID# 209926
city: Madrid
country: Spain
facility: Clinica Universitar de Navarra - Madrid /ID# 210131
city: Madrid
country: Spain
facility: Hosp Univ 12 de Octubre /ID# 209887
city: Valencia
country: Spain
facility: Hospital Univ Dr. Peset /ID# 209884
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: