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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03785184
• Other study ID #: M16-104
• Status: Withdrawn
• Phase: Phase 2
• Start date: April 29, 2019
• Est. completion date: August 22, 2019

Study information

• Verified date: August 2019
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 22, 2019
• Est. primary completion date: August 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• venetoclax
tablet; oral
• lenalidomide
capsule; oral
• dexamethasone
tablet; oral

Locations

Country	Name	City	State
Australia	Flinders Centre for Innovation /ID# 210697	Bedford Park	South Australia
Australia	St. Vincents Hosp Melbourne /ID# 210266	Fitzroy	Victoria
Australia	Austin Hospital /ID# 210268	Heidelberg	Victoria
Australia	Monash Medical Centre /ID# 210269	Melbourne	Victoria
Australia	Westmead Hospital /ID# 210267	Westmead	New South Wales
Canada	Tom Baker Cancer Centre /ID# 208549	Calgary	Alberta
Canada	Hopital Maisonneuver-Rosemont /ID# 208550	Montreal	Quebec
Canada	McGill Univ HC /ID# 208486	Montreal	Quebec
Canada	Princess Margaret Cancer Centr /ID# 208923	Toronto	Ontario
Spain	Hospital Clinic de Barcelona /ID# 209888	Barcelona
Spain	Clinica Universitar de Navarra - Madrid /ID# 210131	Madrid
Spain	Hosp Univ 12 de Octubre /ID# 209887	Madrid
Spain	Hspital Universitario Gregorio Maranon /ID# 209926	Madrid
Spain	Clinica Universitar de Navarra - Pamplona /ID# 209883	Pamplona	Navarra, Comunidad
Spain	Hospital Univ Dr. Peset /ID# 209884	Valencia
United States	Henry Ford Hospital /ID# 208481	Detroit	Michigan
United States	Karmanos Cancer Institute /ID# 208805	Detroit	Michigan
United States	City of Hope /ID# 212211	Duarte	California
United States	Duke University Hospital /ID# 208306	Durham	North Carolina
United States	Marin Cancer Care /ID# 208476	Greenbrae	California
United States	University of California, Los Angeles /ID# 208516	Los Angeles	California
United States	UPMC Hillman Cancer Ctr /ID# 208121	Pittsburgh	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
AbbVie	Celgene Corporation, Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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