A Study of Ixazomib Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

NCT ID: NCT01217957

Last Updated: 2018-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-22
• Study Completion Date: 2018-02-02

Brief Summary

The purpose of Phase 1 of this study was to determine the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of oral ixazomib administered in combination with lenalidomide and low-dose dexamethasone in participants with newly diagnosed multiple myeloma (NDMM). The purpose of Phase 2 of this study was to determine the overall response rate (ORR) and further evaluate the tolerability and toxicity of the combination of oral ixazomib, lenalidomide, and low-dose dexamethasone in patients with NDMM.

Detailed Description

The drug being tested in this study is called ixazomib. Ixazomib was being tested to treat people who had newly diagnosed multiple myeloma who had not previously received systemic treatment. This study was conducted in two Phases. Phase 1 looked at side effects and lab results in people who took ixazomib to determine the MTD and RP2D. Phase 2 looked at overall response rates and side effects in people who took ixazomib.

The study enrolled 15 patients in Phase 1 and 50 patients in Phase 2. Participants in Phase 1 were assigned to cohorts and received ixazomib 1.68, 2.23, 2.97, or 3.95 mg/m^2 in addition to dexamethasone 40 mg and lenalidomide 25 mg. Participants in Phase 2 received ixazomib 4.0 mg fixed dose in addition to dexamethasone 40 mg and lenalidomide 25 mg. In both Phases study treatment was administered in 28-day Cycles as follows: ixazomib Days 1, 8 and 15, dexamethasone Days 1, 8, 15 and 22, and lenalidomide 25 mg Days 1 through 21.

This multi-center trial was conducted in the United States. The overall time to participate in this study was 12, 28-day cycles with the option to continue into a maintenance portion in the absence of disease progression or unacceptable toxicity. Participants made multiple visits to the clinic and a final visit 30 days after last dose of study drug for a follow-up assessment.

Conditions

Multiple Myeloma

Study Design

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

Study Groups

Phase 1: Ixazomib 1.68 mg/m^2 + Lenalidomide + Dexamethasone

In phase 1, ixazomib 1.68 mg/m\^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 1.68 mg/m\^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Lenalidomide

Intervention Type: DRUG

Lenalidomide capsules

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets

Phase 1: Ixazomib 2.23 mg/m^2 + Lenalidomide + Dexamethasone

In phase 1, ixazomib 2.23 mg/m\^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.23 mg/m\^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Lenalidomide

Intervention Type: DRUG

Lenalidomide capsules

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets

Phase 1: Ixazomib 2.97 mg/m^2 + Lenalidomide + Dexamethasone

In phase 1, ixazomib 2.97 mg/m\^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 2.97 mg/m\^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Lenalidomide

Intervention Type: DRUG

Lenalidomide capsules

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets

Phase 1: Ixazomib 3.95 mg/m^2 + Lenalidomide + Dexamethasone

In phase 1, ixazomib 3.95 mg/m\^2, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 3.95 mg/m\^2, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Lenalidomide

Intervention Type: DRUG

Lenalidomide capsules

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets

Phase 2: Ixazomib 4.0 mg + Lenalidomide + Dexamethasone

In phase 2, ixazomib 4.0 mg fixed dose, capsules, orally, once, on Days 1, 8 and 15; plus dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22; and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21 of a 28-day cycle for up to 12 cycles. Cycle 13 and beyond, single agent ixazomib 4.0 mg fixed dose, capsules, orally, once on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Lenalidomide

Intervention Type: DRUG

Lenalidomide capsules

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets

Interventions

Ixazomib

Ixazomib capsules

Intervention Type: DRUG

Lenalidomide

Lenalidomide capsules

Intervention Type: DRUG

Dexamethasone

Dexamethasone tablets

Intervention Type: DRUG

Other Intervention Names

MLN9708; NINLARO®

Eligibility Criteria

Inclusion Criteria

Each patient must meet all of the following eligibility criteria to be enrolled in the study:

• Male or female patients 18 years or older
• Previously untreated multiple myeloma diagnosed according to standard criteria requiring systemic treatment
• Patients must have measurable disease
• Nonsecretory multiple myeloma based upon standard M-component criteria (i.e., measurable serum/urine M-component) is not allowed unless the baseline serum free light chain level (Freelite™) is evaluated Patients must meet clinical laboratory criteria as specified in study protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Female and male patients MUST adhere to the guidelines of the lenalidomide pregnancy prevention program
• Must be able to take concurrent aspirin 325 mg daily
• Voluntary written consent

Exclusion Criteria

• Peripheral neuropathy that is greater or equal to Grade 2
• Female patients who are lactating or pregnant
• Major surgery or radiotherapy within 14 days before the first dose of study drug
• Serious infection requiring systemic antibiotic therapy within 14 days before the first dose of study drug
• Diarrhea greater than Grade 1 based on the National Cancer Institute Common Terminology Criteria for Adverse Events
• Central nervous system involvement.
• Evidence of current uncontrolled cardiovascular conditions within the past 6 months
• Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
• Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
• Known gastrointestinal condition that could interfere with swallowing or the oral absorption or tolerance of ixazomib
• No other prior malignancy within 2 years except nonmelanoma skin cancer or carcinoma in situ of any type if they have undergone complete resection

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

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Rocky Mountain Cancer Center Rose

Denver, Colorado, United States

Cancer Center of Central Connecticut

Southington, Connecticut, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Mt Sinai Medical Center

Miami Beach, Florida, United States

Emory University

Atlanta, Georgia, United States

Harry and Jeannette Weinberg Cancer Center at Franklin Square Hospital

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

New York Presbyterian Hospital - Weill-Cornell

New York, New York, United States

Sarah Cannon Cancer Center

Nashville, Tennessee, United States

W VA University Mary Babb Randolph Cancer Center

Morgantown, West Virginia, United States

The Medical College of Wisconsin, Inc.

Milwaukee, Wisconsin, United States

Countries

United States

References

Gupta N, Yang H, Hanley MJ, Zhang S, Liu R, Kumar S, Richardson PG, Skacel T, Venkatakrishnan K. Dose and Schedule Selection of the Oral Proteasome Inhibitor Ixazomib in Relapsed/Refractory Multiple Myeloma: Clinical and Model-Based Analyses. Target Oncol. 2017 Oct;12(5):643-654. doi: 10.1007/s11523-017-0524-3.

Reference Type: DERIVED

PMID: 28803351 (View on PubMed)

Kumar SK, Berdeja JG, Niesvizky R, Lonial S, Laubach JP, Hamadani M, Stewart AK, Hari P, Roy V, Vescio R, Kaufman JL, Berg D, Liao E, Di Bacco A, Estevam J, Gupta N, Hui AM, Rajkumar V, Richardson PG. Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Lancet Oncol. 2014 Dec;15(13):1503-1512. doi: 10.1016/S1470-2045(14)71125-8. Epub 2014 Nov 14.

Reference Type: DERIVED

PMID: 25456369 (View on PubMed)

Other Identifiers

U1111-1176-7340

Identifier Type: REGISTRY

Identifier Source: secondary_id

C16005

Identifier Type: -

Identifier Source: org_study_id