A Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

A Phase 2, Open-Label, Multicenter, Dose-Escalation and Expansion Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03567616
• Other study ID #: M16-085
• Secondary ID: 2017-004232-11
• Status: Terminated
• Phase: Phase 2
• Start date: October 18, 2018
• Est. completion date: June 18, 2020

Study information

• Verified date: June 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was an open-label, multicenter study designed to evaluate the safety and preliminary efficacy of venetoclax combined with pomalidomide and dexamethasone in participants with relapsed or refractory (R/R) multiple myeloma (MM) who received at least 1 prior line of therapy with documented evidence of progression during or after the participant's last treatment regimen. The study was designed to consist of 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). For Part 2 the participants were to be divided into 2 cohorts, participants positive for t(11;14) translocation and participants negative for t(11;14) translocation.

Description:

Following communication of the results of the primary progression-free survival (PFS) analysis from the Phase 3 BELLINI study (Study M14-031; NCT02755597), the company-sponsored MM studies were placed on partial clinical hold (PCH) in March 2019 by the United States (US) Food and Drug Administration and enrollment was halted. The sponsor did not pursue release of the PCH for this study; therefore, enrollment was not re-opened. In accordance with the terms of the PCH, participants who were deriving clinical benefit were allowed to continue to receive treatment. One participant was still active in Part 1 of the study when the sponsor decided not to pursue release of the PCH (in January 2020) and, therefore, continued to receive treatment and have regular assessments until disease progression. The study was discontinued when the last participant completed study treatment. No participants were enrolled in Part 2 of the study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: June 18, 2020
• Est. primary completion date: June 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Relapsed or refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen

• Measurable disease as described in the protocol

• Received at least 1 prior line of therapy as described in the protocol

• Must meet prior antimyeloma treatment parameters, as described in the protocol, and includes:

• Received at least 2 consecutive cycles of lenalidomide or a lenalidomide-containing regimen

• Refractory to lenalidomide

• Exposed to a proteasome inhibitor (PI) alone or in combination with another agent

• Had a response of partial response (PR) or better to prior therapy based on the investigator's determination of response as defined by International Myeloma Working Group (IMWG) criteria

• Has t(11;14) status as described in the protocol and meets the following criteria:

• For Part 1: MM participants independent of cytogenetic profile

• For Part 2, Arm A: participant must be t(11;14) positive

• For Part 2, Arm B: participant must be t(11;14) negative

• An Eastern Cooperative Oncology Group (ECOG) performance status = 2

• Adequate kidney, liver and hematologic laboratory values

Exclusion Criteria:

• Previous treatment with venetoclax or other BCL-2 inhibitors, or previous treatment with pomalidomide

• Known sensitivity to any IMiDs

• Allogenic or syngeneic stem cell transplant within 6 months before the first dose of study drug or active ongoing graft versus host disease

• Autologous stem cell transplant within 12 weeks before the first dose of study drug

• Known meningeal involvement of MM

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Venetoclax
Tablet; oral
• Pomalidomide
Capsule; oral
• Dexamethasone
Administered orally; for participants over 75 years of age, dexamethasone could have been administered at a 20 mg dose [qw]

Locations

Country	Name	City	State
Spain	Hospital Universitario Germans Trias i Pujol /ID# 200959	Badalona	Barcelona
Spain	Hospital Universitario Vall d'Hebron /ID# 200967	Barcelona
Spain	Hospital Clinico Universitario de Salamanca /ID# 200958	Salamanca
United Kingdom	Univ Hospitals Birmingham NHS Foundation trust /ID# 203188	Birmingham
United Kingdom	Leicester Royal Infirmary /ID# 202238	Leicester	England
United Kingdom	Norfolk and Norwich Univ Hosp /ID# 202240	Norwich	Norfolk
United States	John B. Amos Cancer Center - C /ID# 202055	Columbus	Georgia
United States	Ohio State Cancer Center /ID# 202443	Columbus	Ohio
United States	Duke University Hospital /ID# 200805	Durham	North Carolina
United States	University of Kansas Cancer Center /ID# 201292	Fairway	Kansas
United States	Washington University-School of Medicine /ID# 201287	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Celgene

Countries where clinical trial is conducted

United States,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.	From first dose of study drug until 30 days following last dose of study drug (up to 70 weeks)
Primary	Overall Response Rate (ORR)	ORR is defined as the percentage of participants experiencing a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) using the International Myeloma Working Group (IMWG) 2016 criteria for disease response and progression. CR= negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow; sCR= CR + normal serum free light chain (FLC) ratio and absence of clonal cells in bone marrow; VGPR= serum and urine M-protein detectable by immunofixation but not on electrophoresis or = 90% reduction in serum M-protein level + urine M-protein level < 100 mg per 24 hours; PR= = 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by = 90% or to < 200 mg per 24 hours.	Approximately 15 months
Secondary	Progression-Free Survival (PFS)	PFS is defined as the number of days from the date of first dose of any study drug to the date of disease progression or death, whichever occurs first. All disease progression was to be included regardless of whether the event occurred during or after the participant was taking any study drug.	Approximately 20 months
Secondary	Duration of Response (DOR)	DOR for a given participant is defined as the number of days from the date of that participant's first documented response (Partial Response [PR] or better) to the date of first documented disease progression (PD) or death due to multiple myeloma (MM), whichever occurs first. If the participant with a documented response did not have an event of PD and the participant had not died due to MM, the participant's data was to be censored.	Approximately 15 months
Secondary	Time-to-progression (TTP)	TTP for a given participant is defined as the number of days from the date of first dose to the date of first documented disease progression (PD) or death due to multiple myeloma (MM), whichever occurs first. If the participant did not have an event of PD and the participant had not died due to MM, the participant's data was to be censored.	Approximately 15 months

External Links

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