Phase 1 Pharmacokinetic Study of Oral Ixazomib Plus Lenalidomide and Dexamethasone in Adult Asian Participants With Relapsed and/or Refractory Multiple Myeloma

NCT ID: NCT01645930

Last Updated: 2018-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-17
• Study Completion Date: 2017-04-11

Brief Summary

The purpose of this Phase 1 study is to characterize the pharmacokinetic (PK) and tolerability of oral ixazomib (MLN9708) when administered in combination with lenalidomide and dexamethasone in adult Asian participants with relapsed and/or refractory multiple myeloma.

Detailed Description

The drug being tested in this study was ixazomib. Ixazomib was tested to treat adult Asian people who had relapsed and/or refractory multiple myeloma.

The study enrolled 43 patients. Participants were enrolled to receive:

• Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg.

All participants were asked to take ixazomib capsules orally on Days 1, 8, and 15; lenalidomide capsules, orally, on Days 1 through 21; and dexamethasone tablets, orally, on Days 1, 8, 15, and 22 of a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity (up to 20 cycles).

This multi-center trial was conducted in Singapore, Hong Kong and South Korea. The overall time to participate in this study was up to 577 days. Participants made multiple visits to the clinic, and were contacted 30 days after last dose of study drug for a follow-up assessment.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ixazomib+Lenalidomide+Dexamethasone

Ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15; lenalidomide 25 mg, capsules, orally, once on Days 1 through 21; and dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15, and 22 of a 28-day treatment cycle until progressive disease (PD) or unacceptable toxicity (up to 20 cycles)

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Lenalidomide

Intervention Type: DRUG

Lenalidomide capsules

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets

Interventions

Ixazomib

Ixazomib capsules

Intervention Type: DRUG

Lenalidomide

Lenalidomide capsules

Intervention Type: DRUG

Dexamethasone

Dexamethasone tablets

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female East Asian participants 18 years or older
• Diagnosed Multiple Myeloma according to standard criteria
• Measurable disease as specified in study protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Participants with relapsed and/or refractory Multiple Myeloma who have received 1 to 3 prior therapies
• Meet the clinical laboratories criteria as specified in the protocol
• Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse; must also adhere to the guidelines of the lenalidomide pregnancy prevention program
• Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse and must adhere to the guidelines of the lenalidomide pregnancy prevention program
• Must be able to take concurrent aspirin 325 mg daily
• Voluntary written consent

Exclusion Criteria

• Female participants who are lactating or pregnant
• Major surgery or radiotherapy within 14 days before enrollment
• Infection requiring systematic antibiotics within 14 days before study enrollment
• Central nervous system involvement
• Failure to have fully recovered from the effects of prior chemotherapy regardless of the interval since last treatment
• Systemic treatment with strong inhibitors of cytochrome P450 1A2 (CYP1A2), strong inhibitors of CYP3A, or strong CYP3A inducers, or use of Ginko biloba or St. John's wort within 14 days before study enrollment
• Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome
• Evidence of current uncontrolled cardiovascular conditions
• Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
• Known allergy to any of the study medications
• Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of ixazomib
• Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ
• Ongoing or active systemic infection, active hepatitis B virus infect, active hepatitis C infection, or known human immunodeficiency virus (HIV) positive

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director Clinical Science

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Pokfulam, , Hong Kong

Shatin, , Hong Kong

Singapore, , Singapore

Incheon, , South Korea

Seoul, , South Korea

Countries

Hong Kong; Singapore; South Korea

References

Gupta N, Goh YT, Min CK, Lee JH, Kim K, Wong RS, Chim CS, Hanley MJ, Yang H, Venkatakrishnan K, Hui AM, Esseltine DL, Chng WJ. Pharmacokinetics and safety of ixazomib plus lenalidomide-dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study. J Hematol Oncol. 2015 Sep 4;8:103. doi: 10.1186/s13045-015-0198-1.

Reference Type: DERIVED

PMID: 26337806 (View on PubMed)

Other Identifiers

U1111-1155-5943

Identifier Type: REGISTRY

Identifier Source: secondary_id

HKUCTR-1593

Identifier Type: REGISTRY

Identifier Source: secondary_id

C16013

Identifier Type: -

Identifier Source: org_study_id