NCT02939183 · REGISTRY CONDITION SEARCH

Phase 1b Study Evaluating OPomD in 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: PHASE1
Status at capture: COMPLETED
Registry last update: 2024-09-26

A study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in participants with relapsed refractory multiple myeloma.

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 Who Experienced Dose-Limiting Toxcity (DLT)

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outcome · POSTED

Maximum Tolerated Dose (MTD) of Each Formulation of Oprozomib in Combination With Pomolidomide and Dexamethasone

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outcome · POSTED

Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Oprozomib in Combination With Dexamethasone and/or Pomalidomide)

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outcome · POSTED

Number of Participants With TEAEs and Treatment-emergent Serious AEs (Open-label Roll-over)

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outcome · POSTED

Maximum Observed Concentration (Cmax) of Oprozomib

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outcome · POSTED

Time to Cmax (Tmax) of Oprozomib

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outcome · POSTED

Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Oprozomib

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outcome · POSTED

Best Overall Response (BOR) According to Revised International Myeloma Working Group Uniform Response Criteria (IMWG-URC)

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outcome · POSTED

Overall Response Rate (ORR) According to IMWG-URC

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outcome · POSTED

Number of Participants With Progression Free Survival (PFS) Events

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outcome · POSTED

Kaplan-Meier Estimate of PFS

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outcome · POSTED

Kaplan-Meier Estimate of Duration of Response (DOR)

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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 * Participant must have a pathologically documented, definitively diagnosed, multiple myeloma relapse, or refractory progressive disease after at least 2 lines of therapy for multiple myeloma. Prior therapeutic treatment or regimens must include a proteasome inhibitor and lenalidomide. * Participant must be willing and able to undergo bone marrow aspirate per protocol (with or without bone marrow biopsy per institutional guidelines). * Measurable disease (assessed within 28 days prior to day 1). * Eastern Cooperative Oncology Group (ECOG) performance status of \<= 2. * Other Inclusion Criteria May Apply Exclusion Criteria * Currently receiving treatment in another investigational device or drug study, or less than 28 days or 5 half-lives whichever is shorter since ending treatment on another investigational device or drug study(s). * Previously received an allogeneic stem cell transplant and the occurrence of one or more of the following: received the transplant within 6 months prior to study day 1; received immunosuppressive therapy within the last 3 months prior to study day 1; having signs or symptoms of acute or chronic graft-versus-host disease. * Autologous stem cell transplant \< 90 days prior to study day 1. * Multiple myeloma with IgM subtype. * POEM syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). * Plasma cell leukemia (\> 2.0 X10\^9/L circulating plasma cells by standard differential). * Waldenstrom's macroglobulinemia. * Other Exclusion Criteria May Apply
healthy Volunteers: false
maximum Age: 100 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Oprozomib IR plus dexamethasone
intervention Names
Drug: Immediate Release (IR) Formulation
Drug: Dexamethasone
label
Part 1 Oprozomib Immediate-release (IR) + Dexamethasone
type
EXPERIMENTAL
description
Oprozomib GR plus dexamethasone
intervention Names
Drug: Gastro-Retentive (GR) Formulation
Drug: Dexamethasone
label
Part 1 Oprozomib Gastro-retentive (GR) + Dexamethasone
type
EXPERIMENTAL
description
Oprozomib IR plus pomalidomide and dexamethasone
intervention Names
Drug: Immediate Release (IR) Formulation
Drug: Dexamethasone
Drug: Pomalidomide
label
Part 2 Oprozomib IR + Pomalidomide + Dexamethasone
type
EXPERIMENTAL
description
Oprozomib GR plus pomalidomide and dexamethasone
intervention Names
Drug: Gastro-Retentive (GR) Formulation
Drug: Dexamethasone
Drug: Pomalidomide
label
Part 2 Oprozomib GR + Pomalidomide + Dexamethasone
type
EXPERIMENTAL
description
Oprozomib GR monotherapy, or oprozomib GR plus dexamethasone
intervention Names
Drug: Gastro-Retentive (GR) Formulation
Drug: Dexamethasone
label
Open-label Roll-over
type
EXPERIMENTAL

interventions

arm Group Labels
Part 1 Oprozomib Immediate-release (IR) + Dexamethasone
Part 2 Oprozomib IR + Pomalidomide + Dexamethasone
description
Immediate Release (IR) Formulation
name
Immediate Release (IR) Formulation
type
DRUG
arm Group Labels
Open-label Roll-over
Part 1 Oprozomib Gastro-retentive (GR) + Dexamethasone
Part 2 Oprozomib GR + Pomalidomide + Dexamethasone
description
Gastro-Retentive (GR) Formulation
name
Gastro-Retentive (GR) Formulation
type
DRUG
arm Group Labels
Open-label Roll-over
Part 1 Oprozomib Gastro-retentive (GR) + Dexamethasone
Part 1 Oprozomib Immediate-release (IR) + Dexamethasone
Part 2 Oprozomib GR + Pomalidomide + Dexamethasone
Part 2 Oprozomib IR + Pomalidomide + Dexamethasone
description
Dexamethasone
name
Dexamethasone
type
DRUG
arm Group Labels
Part 2 Oprozomib GR + Pomalidomide + Dexamethasone
Part 2 Oprozomib IR + Pomalidomide + Dexamethasone
description
Pomalidomide
name
Pomalidomide
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 61
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia \> 24 hours); Grade 3 nausea, vomiting and diarrhea \< 3 days; Grade 3 fatigue \< 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count \< 0.5 x 10\^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.
measure
Number of Participants Who Experienced Dose-Limiting Toxcity (DLT)
time Frame
Day 1 to day 28 of cycle 1, where each cycle was 28 days
description
The MTD was the dose with the highest posterior probability of having a DLT rate within the target toxicity interval (15% to 25%), while the posterior probability of excessive/unacceptable toxicity (\>25% to 100%) is \<40%. DLTs were graded using CTCAE version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia \> 24 hours); Grade 3 nausea, vomiting and diarrhea \< 3 days; Grade 3 fatigue \< 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count \< 0.5 x 10\^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.
measure
Maximum Tolerated Dose (MTD) of Each Formulation of Oprozomib in Combination With Pomolidomide and Dexamethasone
time Frame
Day 1 to Day 28 of cycle 1, where each cycle was 28 days
description
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Any clinically significant changes in electrocardiograms, vital signs, physical examination with a neurological assessment and clinical laboratory tests were recorded as TEAEs.
measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Oprozomib in Combination With Dexamethasone and/or Pomalidomide)
time Frame
Day 1 of cycle 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
description
TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Serious TEAEs were any AE meeting at least 1 of the following criteria: fatal; life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event.
measure
Number of Participants With TEAEs and Treatment-emergent Serious AEs (Open-label Roll-over)
time Frame
Day 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration for the open-label roll-over arm was 75.14 weeks

secondary Outcomes

description
The mean Cmax of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
measure
Maximum Observed Concentration (Cmax) of Oprozomib
time Frame
Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
description
The median Tmax of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
measure
Time to Cmax (Tmax) of Oprozomib
time Frame
Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
description
The mean AUClast of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
measure
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Oprozomib
time Frame
Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
description
BOR was the best response per IMWG-URC from best to worst: stringent complete response (sCR; complete response \[CR\], normal serum free light chain ratio, no clonal cells in bone marrow \[BM\]), CR (negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in BM), very good partial response (VGPR; serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein \[urine M-protein level \< 100 mg/24-h\]), partial response (PR; ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or \< 200 mg/24-h), minimal response (MR; 25-49% reduction of serum M-protein and 50-89% in 24-h urinary M-protein, exceeding 200 mg/24-h), stable disease (SD; not CR, VGPR, PR or progressive disease \[PD\]), and PD (≥ 25% increase in serum or urine M-component, development of new or increased size of existing bone lesions or soft tissue plasmacytomas, hypercalcemia attributed to the plasma cell proliferative disorder).
measure
Best Overall Response (BOR) According to Revised International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
time Frame
Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
description
The ORR was defined as the percentage of participants with a BOR of sCR, CR, VGPR, and PR per the IMWG-URC. Complete response (CR): Negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in bone marrow (BM). Stringent CR (sCR): CR and normal serum free light chain ratio and no clonal cells in BM. Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level \< 100 mg/24-h). PR: ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to \< 200 mg/24-h. The 95% confidence intervals (CIs) were estimated using the Clopper-Pearson method.
measure
Overall Response Rate (ORR) According to IMWG-URC
time Frame
Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
description
PFS was defined as the number of months from a participant's first dose of study treatment to the earlier of disease progression or death due to any cause. The number of participants who had a PFS event or who were censored are presented. PFS events were an assessment of progressive disease according to the IMWG-URC or death due to any cause. PFS data was censored: participants alive and no documented disease progression at time of analysis were censored at date of last disease assessment; participants alive with no disease assessment were censored at the first study dose date; participants alive without documented disease progression, with withdrawn consent were censored at date of last disease assessment before consent withdrawal; and for participants who started anti-cancer therapy other than study treatment prior to documentation of disease progression were censored at date of last disease assessment prior to starting new therapy.
measure
Number of Participants With Progression Free Survival (PFS) Events
time Frame
Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
description
PFS was defined as the number of months from a participant's first dose of study treatment to the earlier of disease progression or death due to any cause. Median PFS was estimated using the Kaplan-Meier method. 95% CIs were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. PFS data was censored: participants alive and no documented disease progression at time of analysis were censored at date of last disease assessment; participants alive with no disease assessment were censored at the first study dose date; participants alive without documented disease progression, with withdrawn consent were censored at date of last disease assessment before consent withdrawal; and for participants who started anti-cancer therapy other than study treatment prior to documentation of disease progression were censored at date of last disease assessment prior to starting new therapy.
measure
Kaplan-Meier Estimate of PFS
time Frame
Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
description
DOR, presented in months, was defined as the number of days between the date of the first tumor assessment indicating an objective response (PR or better) through to the subsequent date of progression or death due to any cause, or where applicable date of censoring (date of first progressive disease assessment or death or date of censoring - date of the first objective response result + 1/30.4). Median PFS was estimated using the Kaplan-Meier method. 95% confidence intervals were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.
measure
Kaplan-Meier Estimate of Duration of Response (DOR)
time Frame
Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks

Full study description

brief Summary: A study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in participants with relapsed refractory multiple myeloma.
detailed Description: A multicenter, non-randomized, open-label, dose-exploration study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in participants with relapsed refractory multiple myeloma. The study will be conducted in two parts. Part 1 will evaluate the formulations of oprozomib in combination with dexamethasone only. Part 2 will evaluate the formulations of oprozomib administered at increasing dose levels (dose escalation) in combination with pomalidomide and dexamethasone.

Source references