Multiple Myeloma Clinical Trial
Pharmacokinetics Study of Oral Ixazomib (MLN9708) in Relapsed/Refractory Multiple Myeloma and Advanced Solid Tumors Participants With Normal Renal Function or Severe Renal Impairment
Summary
The purpose of this study is to characterize the single-dose pharmacokinetic (PK) parameters of ixazomib (MLN9708) in cancer participants with either normal renal function or severe renal impairment (RI), including participants with end-stage renal disease (ESRD).
Full Description
The drug tested in this study was called ixazomib (MLN9708). Ixazomib was administered to participants with cancer and either normal renal function or severe renal impairment, including end-stage renal disease (ESRD) requiring hemodialysis. This study characterized the PK, safety and efficacy of ixazomib.
The study enrolled 41 participants (37 multiple myeloma and 4 advanced solid tumor). The study was conducted in 2 parts, Part A and Part B. Participants were enrolled to receive:
Ixazomib 3.0 mg
In Part A, all participants were asked to take one 3 mg ixazomib capsule, orally on Day 1. Participants who tolerated ixazomib in Part A had the option of continuing the study by participating in Part B. In Part B, participants received ixazomib (4, 3, or 2.3 mg per protocol) on Days 1, 8, and 15 of each 28-day cycle until participants experienced disease progression or unacceptable toxicity.
This multicenter trial was conducted at 6 study sites in the United States and Canada. The overall time to participate in this study was 435 days. Participants made multiple scheduled visits to the clinic.
Eligibility Criteria
Inclusion Criteria:
Male or female participants 18 years or older
Participants with multiple myeloma (MM) diagnosed according to standard criteria or participants 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. Participants with multiple myeloma must have had at least 1 prior therapy
A calculated creatinine clearance (CrCl) that meets entry criteria for enrollment (i.e., calculated CrCl either ≥ 90 mL/min for normal renal function or < 30 mL/min for severe renal impairment)
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Female participants 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 participants 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 participants 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 physiologic dosing within 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 Cytochrome P1A2 (CYP1A2), strong and moderate inhibitors of Cytochrome P3A (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
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There are 11 Locations for this study
Atlanta Georgia, 30322, United States
Peoria Illinois, 61615, United States
Fairway Kansas, 66205, United States
Baltimore Maryland, 21201, United States
New York New York, 31406, United States
Oklahoma City Oklahoma, 73104, United States
Nashville Tennessee, 37203, United States
Dallas Texas, 75201, United States
Laredo Texas, 78041, United States
San Antonio Texas, 78229, United States
Toronto Ontario, M5G 2, Canada
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