Pharmacokinetics Study of Oral Ixazomib (MLN9708) in Relapsed/Refractory Multiple Myeloma and Advanced Solid Tumors Participants With Normal Renal Function or Severe Renal Impairment

Millennium Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma; Advanced Solid Tumors

Treatments: Drug: Ixazomib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01830816

165055 (Registry Identifier)

C16015

U1111-1158-2763 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 41 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

41 participants in 3 patient groups

Normal Renal Function: Ixazomib

Experimental group

Description:

In the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: Ixazomib

Severe Renal Impairment: Ixazomib

Experimental group

Description:

In the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: Ixazomib

End-stage Renal Disease: Ixazomib

Experimental group

Description:

In the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: Ixazomib