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

Millennium Pharmaceuticals, Inc.60 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

Ixazomib citrateDRUG

Ixazomib citrate capsules

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (6)

Mayo Clinic- Scottsdale

Scottsdale, Arizona, United States

James R. Berenson, MD, Inc

West Hollywood, California, United States

University of Chicago

Chicago, Illinois, United States

Mayo Clinic

Rochester, Minnesota, United States

Outcomes

Primary Outcomes

Number of Participants Reporting One or More Treatment-Emergent Adverse Events and Serious Adverse Events

An Adverse Event is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Time frame: From the first dose through 30 days after last dose of ixazomib citrate or until the start of subsequent antineoplastic therapy (Up to 354 days)

Neurotoxicity Grading

Neurotoxicity is graded using participant responses to 11 functional questions on a 5-point scale, where 0=Not at all and 4=Very much, using the Functional Assessment of Cancer Therapy/Gynecology Oncology Group - Neurotoxicity Questionnaire, Version 4.0(14). Neurotoxicity subscale is a sum of 11 reversed item scores where each original score is transformed as (4 - score). The highest possible score is 44, and a higher score indicates more neurotoxicity.

Time frame: Cycle 1 Day 1 and End of Study (Up to 354 days)

Secondary Outcomes

Cmax: Maximum Observed Plasma Concentration for MLN2238

Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708).

Time frame: Days 1 and 15 of Cycle 1

Data from ClinicalTrials.gov

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