Overview

This trial is active, not recruiting.

Condition multiple myeloma
Treatments oprozomib, lenalidomide, dexamethasone, cyclophosphamide
Phase phase 1/phase 2
Target proteasome
Sponsor Onyx Therapeutics, Inc.
Start date August 2013
End date February 2017
Trial size 134 participants
Trial identifier NCT01881789, OPZ003

Summary

Phase 1b:

- To establish the maximum tolerated dose (MTD) of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide

- To evaluate the safety and tolerability of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide

Phase 2:

- To estimate the overall response rate (ORR) and complete response rate (CRR)

- To evaluate the safety and tolerability of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide

Secondary Objectives:

- To evaluate population pharmacokinetic (PK) parameter estimates of oprozomib and variability in these estimates when administered in combination with dexamethasone and lenalidomide or oral cyclophosphamide

- To estimate the duration of response (DOR)

- To estimate progression-free survival (PFS)

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Subjects will receive oprozomib administered orally, once daily on Days 1, 2, 8, 9, 15,16, 22 and 23 in combination with lenalidomide at a dose of 25 mg on Days 1-21, and dexamethasone at a dose of 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycles.
oprozomib Oprozomib ER tablets
Subjects will receive Oprozomib extended release (ER) Tablets (hereafter referred to as oprozomib) administered orally, once daily on 1, 2, 8, 9, 15,16, 22 and 23 of 28-day cycles
lenalidomide Revlimid
Subjects will receive lenalidomide 25 mg on Days 1-21 of 28 day cycles
dexamethasone
Subjects will receive dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23 of 28 day cycles
(Experimental)
Subjects will receive oprozomib administered orally, once daily on Days 1, 2, 8, 9, 15, 16, 22 and 23 in combination with oral cyclophosphamide at a dose of 300 mg/m2 on Days 1, 8, and 15, and dexamethasone at a dose of 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycles
oprozomib Oprozomib ER tablets
Subjects will receive Oprozomib extended release (ER) Tablets (hereafter referred to as oprozomib) administered orally, once daily on 1, 2, 8, 9, 15,16, 22 and 23 of 28-day cycles
dexamethasone
Subjects will receive dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23 of 28 day cycles
cyclophosphamide Cytoxan
Subjects will receive cyclophophamide 300 mg/m2 on Days 1, 8 and 15 of 28 day cycles

Primary Outcomes

Measure
Maximum Tolerated Dose (MTD)
time frame: 6 months
Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: 36 months
Overall Response Rate (ORR)
time frame: 14 months
Complete Response Rate (CRR)
time frame: 17 months

Secondary Outcomes

Measure
Population Pharmacokinetic (PK) Parameters - Apparent Clearance
time frame: 18 months
Population Pharmacokinetic (PK) Parameters - Volume of Distribution
time frame: 18 months
Duration of Response (DOR)
time frame: 42 months
Progression-Free Survival (PFS)
time frame: 42 months

Eligibility Criteria

Male or female participants at least 18 years old.

Key Inclusion Criteria: - Newly diagnosed, symptomatic multiple myeloma patients for whom treatment is indicated per the 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) Key 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

Additional Information

Official title Phase 1b/2, Multicenter, Open-label Study of Oprozomib and Dexamethasone, in Combination With Lenalidomide or Oral Cyclophosphamide in Patients With Newly Diagnosed Multiple Myeloma
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Onyx Pharmaceuticals.