Oprozomib and Dexamethasone,in Combination With Lenalidomide or Oral Cyclophosphamide to Treat Newly Diagnosed Multiple Myeloma

NCT ID: NCT01881789

Last Updated: 2022-11-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-28
• Study Completion Date: 2019-09-23

Brief Summary

The primary objectives of this study included the following:

Phase 1b:

• To establish the maximum tolerated dose (MTD) of oprozomib given in combination with lenalidomide and dexamethasone (ORd) or with cyclophosphamide and dexamethasone (OCyd)
• To evaluate the safety and tolerability of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide

Phase 2:

• To estimate the antitumor activity of each combination regimen, as measured by overall response rate (ORR) and complete response rate (CRR)
• To evaluate the safety and tolerability of each combination regimens, as assessed by the type, incidence, severity and seriousness of adverse events, and abnormalities in selected laboratory analytes

Detailed Description

Phase 1b used a standard 3 + 3 dose-escalation scheme to determine the MTD. For each combination regimen, oprozomib doses were to be escalated in sequential cohorts of 3 participants with expansion to up to 6 participants if a dose-limiting toxicity (DLT) was observed in 1 of the first 3 participants. The doses of lenalidomide, cyclophosphamide, and dexamethasone were to remain fixed in all dose cohorts.

The phase 2 portion of the study was to include up to 35 additional participants in each of the 2 combination regimens, treated at the recommended phase 2 dose (RP2D) of oprozomib that was identified during the phase 1b portion of the study in order to better characterize safety and tolerability, and antimyeloma activity.

This study was stopped by sponsor decision during the dose escalation in phase 1b prior to initiation of phase 2.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oprozomib 150 mg 5/14 + Lenalidomide + 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 lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.

Group Type: EXPERIMENTAL

Oprozomib

Intervention Type: DRUG

Extended release (ER) tablets administered orally

Lenalidomide

Intervention Type: DRUG

Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.

Dexamethasone

Intervention Type: DRUG

Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants \> 75 years of age, at the discretion of the investigator.

Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone

Participants received oprozomib 180 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 lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.

Group Type: EXPERIMENTAL

Oprozomib

Intervention Type: DRUG

Extended release (ER) tablets administered orally

Lenalidomide

Intervention Type: DRUG

Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.

Dexamethasone

Intervention Type: DRUG

Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants \> 75 years of age, at the discretion of the investigator.

Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone

Participants received oprozomib 210 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 lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.

Group Type: EXPERIMENTAL

Oprozomib

Intervention Type: DRUG

Extended release (ER) tablets administered orally

Lenalidomide

Intervention Type: DRUG

Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.

Dexamethasone

Intervention Type: DRUG

Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants \> 75 years of age, at the discretion of the investigator.

Oprozomib 210 mg 2/7 + Lenalidomide + 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 lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.

Group Type: EXPERIMENTAL

Oprozomib

Intervention Type: DRUG

Extended release (ER) tablets administered orally

Lenalidomide

Intervention Type: DRUG

Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.

Dexamethasone

Intervention Type: DRUG

Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants \> 75 years of age, at the discretion of the investigator.

Oprozomib 240 mg 2/7 + Lenalidomide + 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 lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.

Group Type: EXPERIMENTAL

Oprozomib

Intervention Type: DRUG

Extended release (ER) tablets administered orally

Lenalidomide

Intervention Type: DRUG

Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.

Dexamethasone

Intervention Type: DRUG

Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants \> 75 years of age, at the discretion of the investigator.

Oprozomib 210 mg 2/7 + Cyclophosphamide + 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 oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.

Group Type: EXPERIMENTAL

Oprozomib

Intervention Type: DRUG

Extended release (ER) tablets administered orally

Dexamethasone

Intervention Type: DRUG

Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants \> 75 years of age, at the discretion of the investigator.

Cyclophosphamide

Intervention Type: DRUG

Administered orally at 300 mg/m² (up to a maximum of 600 mg) on days 1, 8, and 15 of each 28-day cycle for a maximum of 8 cycles of therapy (approximately 8 months).

Interventions

Oprozomib

Extended release (ER) tablets administered orally

Intervention Type: DRUG

Lenalidomide

Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.

Intervention Type: DRUG

Dexamethasone

Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants \> 75 years of age, at the discretion of the investigator.

Intervention Type: DRUG

Cyclophosphamide

Administered orally at 300 mg/m² (up to a maximum of 600 mg) on days 1, 8, and 15 of each 28-day cycle for a maximum of 8 cycles of therapy (approximately 8 months).

Intervention Type: DRUG

Other Intervention Names

Oprozomib ER tablets; Revlimid; Cytoxan

Eligibility Criteria

Inclusion Criteria

• Newly diagnosed, symptomatic multiple myeloma patients for whom treatment is indicated per the National Comprehensive Cancer Network (NCCN) guidelines, and for whom a hematopoietic stem cell transplant is not planned or scheduled during the study or are considered ineligible for hematopoietic stem cell transplant, with measurable disease
• Creatinine clearance of ≥ 50 mL/min (measured or calculated using the Cockcroft and Gault formula)

Exclusion Criteria

• Any prior systemic antimyeloma therapy except oral steroids (dexamethasone up to a total dose of 160 mg or equivalent within 14 days prior to the first dose of study treatment). Use of topical or inhaled steroids is acceptable
• Radiation therapy within 2 weeks prior to first dose
• Major surgery within 3 weeks prior to first dose
• Active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose
• Clinical significant gastrointestinal bleeding in the 6 months prior to Cycle 1 Day 1 (C1D1) first dose
• Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of first dose
• Other malignancy within the past 3 years except those considered cured by surgical resection including some cases of: with the exception of adequately treated basal or squamous cell carcinoma of the skin, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the breast or cervix, carcinoma in situ of the breast, prostate cancer with Gleason Score 6 or less with stable prostate specific antigen levels, or cancer considered cured by surgical resection

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Clearview Cancer Institute

Huntsville, Alabama, United States

Providence St. Joseph's Hospital

Burbank, California, United States

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Monterey Bay Oncology Corp DBA Pacific Cancer Care

Salinas, California, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

H. Lee Moffit Cancer Center & Research Institute

Tampa, Florida, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Center for Cancer & Blood Disorders

Bethesda, Maryland, United States

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20130410

Identifier Type: OTHER

Identifier Source: secondary_id

OPZ003

Identifier Type: -

Identifier Source: org_study_id