Overview

This trial is active, not recruiting.

Conditions multiple myeloma, advanced solid tumors
Treatment ixazomib (mln9708)
Phase phase 1
Sponsor Millennium Pharmaceuticals, Inc.
Start date September 2013
End date August 2015
Trial size 28 participants
Trial identifier NCT01830816, 165055, 2012-004516-64, C16015, U1111-1158-2763

Summary

This is a phase 1/1b, open-label, multicenter study of oral ixazomib (MLN9708)designed to assess the pharmacokinetics (PK) of single dose ixazomib in patients with normal renal function and in patients with severe renal impairment (RI) (according to Cockcroft-Gault estimates). Twenty-eight PK-evaluable patients will be enrolled in either 1 of the 2 arms of the study.

Arm 1: (N = 12): Normal renal function (creatinine clearance [CrCl] ≥ 90 mL/min)

Arm 2: (N = 16): Severe RI (CrCl < 30 mL/min) including at least 6 patients with ESRD, defined as renal failure requiring hemodialysis

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
In the 15 day period that constitutes Part A of the trial, patients will receive a single oral dose of ixazomib (MLN9708) capsule on Day 1. Patients from Part A will then have the option of continuing the study by participating in Part B, starting immediately after Part A, where they will receive ixazomib (MLN9708) on Days 1, 8, and 15 of a 28-day cycle. In Part B at the discretion of the investigator, dexamethasone 40 mg may be administered to patients with RRMM on Days 1, 8, 15 and 22 (20 mg if >75 years old) of each 28-day cycle.
ixazomib (mln9708)
(Experimental)
In the 15 day period that constitutes Part A of the trial, patients will receive a single oral dose of ixazomib (MLN9708) capsule on Day 1 of a 15-day cycle. Patients from Part A will then have the option of continuing the study by participating in Part B, starting immediately after Part A, where they will receive ixazomib (MLN9708) on Days 1, 8, and 15 of a 28-day cycle. In Part B at the discretion of the investigator, dexamethasone 40 mg may be administered to patients with RRMM on Days 1, 8, 15 and 22 (20 mg if >75 years old) of each 28-day cycle.
ixazomib (mln9708)

Primary Outcomes

Measure
Mean Single-dose Maximum (peak) Concentration (Cmax) of Ixazomib (MLN9708)
time frame: Assessed on Days 1-15 of Part A
Time to Reach the Maximum Plasma Concentration (Cmax) of Ixazomib (MLN9708)
time frame: Assessed on Days 1-15 of Part A
Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Time of Last Quantifiable Concentration (AUC0-last) of Ixazomib (MLN9708)
time frame: Assessed on Days 1-15 of Part A

Secondary Outcomes

Measure
Number of Adverse Events
time frame: From administration of the first dose of study drug and through 30 days after the last dose of study drug, approximately 13 months
Number of Patients with Overall Response (OR) in RRMM Patients
time frame: Assessed every 8 weeks (length of the endpoint assessment period is projected to be approximately 13 months)
Duration of Response in RRMM patients
time frame: Assessed every 8 weeks until disease progression, approximately 13 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Male or female patients 18 years or older - Patients with multiple myeloma (MM) diagnosed according to standard criteria or patients with a diagnosis of an advanced malignant solid tumor for which standard, curative, or life prolonging treatment does not exist or is no longer effective. Patients with multiple myeloma must have had at least 1 prior therapy - Patients with relapsed/refractory multiple myeloma after at least 1 prior therapy - A calculated creatinine clearance (CrCl) that meets entry criteria for enrollment (ie, calculated CrCl either ≥ 90 or < 30 mL/min - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 - Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception through 90 days after the last dose of study drug or agree to practice true abstinence - Male patients who agree to practice effective barrier contraception through 90 after the last dose of study drug or agree to practice true abstinence - Voluntary written informed consent - Suitable venous access Exclusion Criteria: - Female patients who are pregnant or lactating and breastfeeding - Failure to have recovered from clinically significant effects of prior chemotherapy (defined as toxicity greater than Grade 1 with the exception of alopecia) - Major surgery or radiotherapy within 14 days before study drug administration - Dexamethasone (or equivalent systemic steroid) higher than the physiologic dosing with 7 days before study drug administration - Central nervous system involvement - Infection requiring IV antibiotic therapy or other serious infection within 14 days prior to first dose of study drug - Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, myeloproliferative syndrome, or primary amyloidosis (with the exception of patients in whom amyloidosis has been documented as a complication of MM, who will be evaluated on a case-by-case basis for trial participation) - Systemic treatment with strong and moderate inhibitors of CYP1A2, strong and moderate inhibitors of CYP3A, or clinically significant CYP3A inducers or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study drug - Evidence of uncontrolled cardiovascular conditions - Ongoing or active infection, or known human immunodeficiency virus (HIV) positive - Comorbid systemic illness or psychiatric illness that could interfere with study completion - Known allergy to study medications - Inability to swallow oral medication or condition that could interfere with oral absorption or tolerance of treatment

Additional Information

Official title Phase 1/1b Pharmacokinetics Study of Oral Ixazomib (MLN9708) in Relapsed/Refractory Multiple Myeloma and Advanced Solid Tumors Patients With Normal Renal Function or Severe Renal Impairment
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Millennium Pharmaceuticals, Inc..
Location data was received from the National Cancer Institute and was last updated in April 2016.