Clinical trial NCT01645930: Phase 1 Pharmacokinetic Study of Oral Ixazomib Plus Lenalidomide and Dexamethasone in Adult Asian Participants With Relapsed and/or Refractory Multiple Myeloma
Official title: A Phase 1 Pharmacokinetic and Tolerability Study of Oral MLN9708 Plus Lenalidomide and Dexamethasone in Adult Asian Patients With Relapsed and/or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-07-20
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for Ixazomib
timeFrame: Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose
measure: Cmax: Maximum Observed Plasma Concentration for Ixazomib
timeFrame: Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
timeFrame: Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
timeFrame: Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib
timeFrame: Cycle 1, Day 1 pre-dose and multiple time-points (up to 168 hours) post-dose
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Ixazomib
timeFrame: Cycle 1, Day 15 pre-dose and multiple time-points (up to 336 hours) post-dose
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (up to Day 28)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities Reported as Adverse Events of ≥Grade 3 Intensity
timeFrame: From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)
measure: Number of Participants With Clinically Significant Vital Signs Reported as Adverse Events
timeFrame: From the first dose of study drug through 30 days after the last dose of study drug (up to 577 days)
Secondary outcomes:
measure: Percentage of Participants With Confirmed Best Response Category
timeFrame: From Cycle 1, Day 1 to Cycle 3, Day 1 until disease progression (approximately 20 months)
measure: Duration of Response (DOR)
timeFrame: From date of documentation of a confirmed response to date of progressive disease, (approximately 20 months)
Other outcomes:
Locations:
city: Pokfulam
country: Hong Kong
city: Shatin
country: Hong Kong
city: Incheon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Singapore
country: Singapore
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: 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.