Study Evaluating the Safety and Tolerability of Weekly Dosing of Oral IXAZOMIB in Adult Patients With Relapsed and Refractory Multiple Myeloma

Millennium Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Ixazomib citrate

Study type: Interventional

Funder types: Industry

Identifiers

NCT00963820

C16004

U1111-1166-8401 (Other Identifier)

Details and patient eligibility

About

The primary objective of this study is to determine the safety profile, tolerability, and maximum tolerated dose of ixazomib citrate (MLN9708) when taken orally on a weekly dosing schedule by patients with relapsed and refractory multiple myeloma (RRMM). Secondary objectives include pharmacokinetics and response rates.

Full description

The drug being tested in this study is called ixazomib citrate (MLN9708). Ixazomib citrate is being tested for people who have multiple myeloma who have relapsed after treatment or become unresponsive to treatment.

This study will determine the maximum tolerated dose (MTD) of ixazomib citrate using a dose escalation scheme. Once MTD is established, participants will be enrolled at MTD into one of the 4 expansion cohorts to characterize the safety, tolerability and efficacy of MLN9708. Blood samples for safety labs, hematology, serum chemistry and pharmacokinetic evaluations will be obtained at the timepoints specified. Disease response assessment is to be performed on the first day of every other cycle beginning with Cycle 3.

The study will enroll approximately 60 patients. All participants will receive treatment with ixazomib citrate. This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 60 days, and participants will make 12-16 visits to the clinic for study procedures.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

• Adult patients with multiple myeloma who have relapsed following at least 2 lines of therapy.
• Patients must have measurable disease.
• Appropriate functional status, including the recovery from the effects of prior antineoplastic therapy, and acceptable organ function as described in the protocol.
• Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
• Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse.
• Willing and able to give written informed consent.
• Suitable venous access for study-required blood sampling.

Exclusion criteria

• Peripheral neuropathy that is greater or equal to Grade 2.
• Major surgery or, serious infections, or infections that required systemic antibiotic therapy within 14 days before the first dose of study drug.
• Life-threatening illness unrelated to cancer.
• Diarrhea that is greater than Grade 1 as outlined in the protocol
• Systemic antineoplastic or radiation therapy within 14 days or cytotoxic agents, or treatment with any investigational products within 21 days before the first dose of study treatment.
• Treatment with any investigational proteasome inhibitor.
• Systemic treatment with prohibited medications that are outlined in the protocol within 14 days of study treatment.
• Ongoing therapy with corticosteroids greater than 10mg of prednisone or its equivalent per day.
• Central nervous system involvement.
• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction 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 (GI) disease or GI procedure that could interfere with the oral absorption of tolerance of IXAZOMIB including difficulty swallowing.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 12 patient groups

0.24 mg/m^2

Experimental group

Description:

Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate

Treatment:

Drug: Ixazomib citrate

0.48 mg/m^2

Experimental group

Description:

Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Treatment:

Drug: Ixazomib citrate

0.80 mg/m^2

Experimental group

Description:

Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Treatment:

Drug: Ixazomib citrate

1.20 mg/m^2

Experimental group

Description:

Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period.

Treatment:

Drug: Ixazomib citrate

1.68 mg/m^2

Experimental group

Description:

Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Treatment:

Drug: Ixazomib citrate

2.23 mg/m^2

Experimental group

Description:

Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Treatment:

Drug: Ixazomib citrate

2.97 mg/m^2

Experimental group

Description:

Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Treatment:

Drug: Ixazomib citrate

3.95 mg/m^2

Experimental group

Description:

Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Treatment:

Drug: Ixazomib citrate

Relapsed and Refractory (RR)

Experimental group

Description:

Ixazomib citrate, 2.97 mg/m\^2 established Maximum Tolerated Dose (MTD), capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Treatment:

Drug: Ixazomib citrate

VELCADE-Relapsed (VR)

Experimental group

Description:

Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Treatment:

Drug: Ixazomib citrate

PI naïve

Experimental group

Description:

Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Treatment:

Drug: Ixazomib citrate

Carfilzomib

Experimental group

Description:

Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Treatment:

Drug: Ixazomib citrate