NCT03567616 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: TERMINATED
Registry last update: 2021-06-30

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Adverse Events

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Progression-Free Survival (PFS)

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

Time-to-progression (TTP)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Venetoclax (400 mg oral \[PO\], once daily \[QD\]) administered with pomalidomide (4 mg PO, QD) and dexamethasone (40 mg once weekly \[qw\]) in 28-day cycles until documented disease progression, documented unacceptable toxicity, withdrawal of consent, or the participant met other criteria for discontinuation per study protocol
intervention Names
Drug: Venetoclax
Drug: Pomalidomide
Drug: Dexamethasone
label
Part 1: Dose Escalation
type
EXPERIMENTAL
description
Participants positive for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral \[PO\], once daily \[QD\]) and dexamethasone (40 mg once weekly \[qw\])
intervention Names
Drug: Venetoclax
Drug: Pomalidomide
Drug: Dexamethasone
label
Part 2: Dose Expansion, t(11;14) positive
type
EXPERIMENTAL
description
Participants negative for t(11;14) translocation were to receive the venetoclax dose determined to be safe in Part 1 as well as pomalidomide (4 mg oral \[PO\], once daily \[QD\]) and dexamethasone (40 mg once weekly \[qw\])
intervention Names
Drug: Venetoclax
Drug: Pomalidomide
Drug: Dexamethasone
label
Part 2: Dose Expansion, t(11;14) negative
type
EXPERIMENTAL

interventions

arm Group Labels
Part 1: Dose Escalation
Part 2: Dose Expansion, t(11;14) negative
Part 2: Dose Expansion, t(11;14) positive
description
Tablet; oral
name
Venetoclax
other Names
ABT-199
GDC-0199
Venclexta
type
DRUG
arm Group Labels
Part 1: Dose Escalation
Part 2: Dose Expansion, t(11;14) negative
Part 2: Dose Expansion, t(11;14) positive
description
Capsule; oral
name
Pomalidomide
other Names
Pomalyst
type
DRUG
arm Group Labels
Part 1: Dose Escalation
Part 2: Dose Expansion, t(11;14) negative
Part 2: Dose Expansion, t(11;14) positive
description
Administered orally; for participants over 75 years of age, dexamethasone could have been administered at a 20 mg dose \[qw\]
name
Dexamethasone
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SEQUENTIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 8
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Number of Participants With Adverse Events
time Frame
From first dose of study drug until 30 days following last dose of study drug (up to 70 weeks)
description
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.
measure
Overall Response Rate (ORR)
time Frame
Approximately 15 months

secondary Outcomes

description
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.
measure
Progression-Free Survival (PFS)
time Frame
Approximately 20 months
description
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.
measure
Duration of Response (DOR)
time Frame
Approximately 15 months
description
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.
measure
Time-to-progression (TTP)
time Frame
Approximately 15 months

Full study description

brief 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.
detailed 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.

Source references

references

citation
Gasparetto C, Bowles KM, Abdallah AO, Morris L, Mander G, Coppola S, Wang J, Ross JA, Bueno OF, Arriola E, Mateos MV. A Phase II Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2021 Nov;21(11):775-784. doi: 10.1016/j.clml.2021.07.029. Epub 2021 Aug 1.
pmid
34551886
type
DERIVED