A Study of Oprozomib, Pomalidomide, and Dexamethasone in Adults With Primary Refractory or Relapsed and Refractory Multiple Myeloma

NCT ID: NCT01999335

Last Updated: 2021-04-27

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-30

Study Completion Date

2019-04-25

Brief Summary

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The purpose of the Phase 1 part of the study is to determine the maximum tolerated dose and assess the safety, tolerability and activity of oprozomib in combination with pomalidomide and dexamethasone in adults with primary refractory or relapsed and refractory multiple myeloma.

The purpose of the Phase 3 part of the study is to compare the efficacy for adults with primary refractory or relapsed and refractory multiple myeloma who are randomized to either oprozomib or placebo in combination with pomalidomide and dexamethasone.

Detailed Description

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This was a phase 1b/3, multicenter study composed of 2 parts: part 1 was a phase 1b, open-label, dose-escalation and dose-expansion component and part 2 was to have been a phase 3, placebo-controlled, double-blind, randomized component. Part 2 was not conducted.

The Phase 1 dose-escalation portion of the study followed a standard 3 + 3 dose-escalation design. For each of the 2 schedules, groups of 3 to 6 patients were enrolled. The starting doses of oprozomib were 150 and 210 mg in the 5/14 and 2/7 schedules, respectively. The starting dose of pomalidomide was 4 mg in both schedules. As long as \< 33% of patients experienced a dose-limiting toxicity (DLT) in a given cohort, the dose of oprozomib was escalated in 30-mg increments for successive cohorts.

Once the recommended dose and schedule for the expansion phase had been selected, additional participants were enrolled in the dose expansion portion of part 1 to continue the evaluation of the safety and efficacy of the regimen and determine the recommended phase 3 dose. Enrollment was halted during the dose expansion phase and part 2 was not conducted.

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Oprozomib 150 mg 5/14 + Pomalidomide 4 mg + Dexamethasone

Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Oprozomib

Intervention Type DRUG

Extended release (ER) tablets administered orally

Pomalidomide

Intervention Type DRUG

Capsules for oral administration

Dexamethasone

Intervention Type DRUG

Tablets for oral administration

Oprozomib 150 mg 5/14 + Pomalidomide 2 mg + Dexamethasone

Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with pomalidomide 2 mg/day on days 1 to 21 and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Oprozomib

Intervention Type DRUG

Extended release (ER) tablets administered orally

Pomalidomide

Intervention Type DRUG

Capsules for oral administration

Dexamethasone

Intervention Type DRUG

Tablets for oral administration

Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone

Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Oprozomib

Intervention Type DRUG

Extended release (ER) tablets administered orally

Pomalidomide

Intervention Type DRUG

Capsules for oral administration

Dexamethasone

Intervention Type DRUG

Tablets for oral administration

Oprozomib 240 mg 2/7 + Pomalidomide 4 mg + Dexamethasone

Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Oprozomib

Intervention Type DRUG

Extended release (ER) tablets administered orally

Pomalidomide

Intervention Type DRUG

Capsules for oral administration

Dexamethasone

Intervention Type DRUG

Tablets for oral administration

Oprozomib 210 mg 2/7 + Pomalidomide 4 mg + Dexamethasone: Expansion Phase

Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with pomalidomide 4 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle until disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Oprozomib

Intervention Type DRUG

Extended release (ER) tablets administered orally

Pomalidomide

Intervention Type DRUG

Capsules for oral administration

Dexamethasone

Intervention Type DRUG

Tablets for oral administration

Interventions

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Oprozomib

Extended release (ER) tablets administered orally

Intervention Type DRUG

Pomalidomide

Capsules for oral administration

Intervention Type DRUG

Dexamethasone

Tablets for oral administration

Intervention Type DRUG

Other Intervention Names

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POMALYST®

Eligibility Criteria

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Inclusion Criteria

1. Multiple myeloma that is primary refractory or relapsed and refractory after at least 2 lines of standard for multiple myeloma including:

1. ≥ 2 consecutive cycles of both bortezomib and lenalidomide or thalidomide (alone or in combination)
2. In the dose-expansion and Phase 3 portions of the study only: In addition to the above, treatment with adequate alkylator therapy, defined as:

i. High-dose melphalan or other alkylating agent as conditioning for autologous or allogeneic stem cell transplant (SCT), or ii. ≥ 6 cycles of induction therapy, or iii. Progressive disease after ≥ 2 cycles
2. Disease progression on or within 60 days of completion of the last therapy
3. Measurable disease as indicated by 1 or more of the following:

1. Serum M-protein ≥ 500 mg/dL
2. Urine M-protein ≥ 200 mg/24 h
3. For patients without measurable serum or urine M protein, serum free light chain (SFLC): Involved free light chain (FLC) concentration ≥ 10 mg/dL provided SFLC ratio is abnormal
4. Males and females ≥ 18 years old
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

Exclusion Criteria

1. Systemic chemotherapy with approved or investigational anticancer therapeutics, intended to treat underlying malignancy, within 3 weeks before the first dose or 6 weeks for antibody therapy
2. Dexamethasone at cumulative doses greater than 160 mg or equivalent within 21 days prior to the first dose of study treatment is not allowed. Use of topical or inhaled steroids is acceptable.
3. Radiation therapy within 3 weeks before first dose. Radioimmunotherapy within 8 weeks before first dose.
4. Plasmapheresis is not permitted at any time during the Screening period or while the subject is receiving study treatment. If a subject has started Screening procedures requiring plasmapheresis, or is anticipated to require plasmapheresis during or after the Screen
5. Autologous SCT within 8 weeks or allogeneic SCT within 16 weeks prior to initiation of study treatment. Patients with prior allogeneic SCT should not have evidence of moderate-to-severe graft-versus-host disease (as defined in Filipovich 2005).
6. Known hypersensitivity to any immunomodulatory drugs (IMiDs), including Grade 4 rash
7. Prior treatment of any duration with pomalidomide
8. Known hypersensitivity or intolerance to dexamethasone
9. Prior exposure to oprozomib
10. Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months before first dose.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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California Cancer Associates For Research and Exellence, cCare

Encinitas, California, United States

Site Status

James R. Berenson, MD, Inc.

West Hollywood, California, United States

Site Status

Innovative Clinical Research Institute

Whittier, California, United States

Site Status

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Site Status

Oncology Hematology West PC, dba Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status

Weill Cornell Medical College-New York Presbyterian Hospital

New York, New York, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Willamette Valley Cancer Institute and Research Center

Springfield, Oregon, United States

Site Status

Abramson Cancer Center of the University of Pennsylvania at Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Tennessee Oncology, PLLC / Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Cancer Care Centers of South Texas-HOAST

San Antonio, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Virginia Oncology Associates

Norfolk, Virginia, United States

Site Status

Yakima Valley Memorial Hospital/North Star Lodge

Yakima, Washington, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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20130411

Identifier Type: OTHER

Identifier Source: secondary_id

OPZ007

Identifier Type: -

Identifier Source: org_study_id

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