Overview

This trial is active, not recruiting.

Condition multiple myeloma
Treatment ixazomib + lenalidomide + dexamethasone
Phase phase 1/phase 2
Sponsor Millennium Pharmaceuticals, Inc.
Start date November 2011
End date October 2013
Trial size 64 participants
Trial identifier NCT01383928, C16008

Summary

This will be a phase 1/2, multicenter, open-label study using the oral formulation of IXAZOMIB administered twice weekly in combination with lenalidomide and low-dose dexamethasone. Both phases of the study will include patients who have newly diagnosed multiple myeloma and have not previously received systemic treatment.

Both the phase 1 and the phase 2 portions of the study will include induction therapy consisting of 1 year of therapy followed by maintenance therapy that will continue until progressive disease or unacceptable toxicity. Maintenance therapy will be IXAZOMIB alone on Days 1,4,8, & 11 of a 21-day cycle.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
ixazomib + lenalidomide + dexamethasone
Ph 1: Patients will receive escalating doses of IXAZOMIB orally on Days 1,4,8&11; plus dexamethasone orally on Days 1,2,4,5,8,9,11&12 at 20mg in Cycles 1-8/10mg in Cycles 9-16 & lenalidomide 25mg orally on Days 1-14 of a 21-day cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients who have stable or responding disease will continue treatment in the maintenance therapy portion of the study. Ph 2: Patients will receive IXAZOMIB orally at the maximum tolerated dose or recommended phase 2 dose on Days 1,4,8,11, plus dexamethasone orally on Days 1,2,4,5,8,9,11&12 at 20mg in Cycles 1-8/10mg in Cycles 9-16 and lenalidomide 25mg orally on Days 1-14 of a 21-day cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease will continue treatment in the maintenance therapy portion of the study.

Primary Outcomes

Measure
Maximum Tolerated Dose (MTD) and Recommended phase 2 dose of IXAZOMIB (phase 1)
time frame: Dose Limiting Toxcities determined in Cycle 1 to define MTD; MTD and adverse events monitored throughout the study will inform the recommended phase 2 dose, approximately 1 year
Number of patients with complete response and very partial response rate (phase 2)
time frame: Patients will be assessed after each Cycle 1-4 and then every 2 cycles until disease progression, approximately 2 years
Number of grade 3 or higher adverse events, all serious adverse events, and treatment discontinuation (phase 2)
time frame: From screening period through 30 days after the last dose of study drug or until the start of subsequent antineoplastic therapy, approximately 1 year and 30 days

Secondary Outcomes

Measure
Number of patients with response (phase 1)
time frame: After each Cycle 1-4 and every two cycles thereafter; at end of treatment; and during progression-free survival follow-up (if applicable), expected duration approximately 2 years
Time to response (phase 2)
time frame: From the first dose of study treatment to the date of first documentation of a confirmed response, approximately 1 year
Duration of response (phase 2)
time frame: From the date of first documentation of a confirmed response to the date of progressive disease, approximately 1 year
Time to progression (phase 2)
time frame: From the first dose of study treatment to the date of first documented progressive disease, approximately 3 years
Number of patients with progression free survival (phase 2)
time frame: From the first dose of study treatment to the date of first documented progressive disease or death, approximately 3 years
Number of patients with overall survival (phase 2)
time frame: From the first dose of study treatment to date of death, approximately 6 years
Maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and area under the plasma concentration-time curve (AUC) (phase 1)
time frame: At multiple time points throughout Cycles 1-3, for approximately 43 days
Number of patients with overall response (phase 2)
time frame: After Cycles 1-4 and every other cycle thereafter; at end of treatment; and during progression-free survival follow-up (if applicable), expected duration approximately 2 years
Number of patients with complete response + very good partial response (phase 2)
time frame: After Cycles 4, 8, and 16, approximately 2 years
Number of patients with complete response, stringent complete response, very good partial response, near complete response, partial response, and minimal response (phase 2)
time frame: After Cycles 1-4 and every other cycle thereafter; at end of treatment; and during progression-free survival follow-up (if applicable), expected duration approximately 2 years
Number of patients with 1-year survival (phase 2)
time frame: 1 year after first dose of study treatment in the last patient treated

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Male or female patients 18 years or older - Symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage diagnosed according to standard criteria - Measurable disease as specified in study protocol - Hematologic, liver, and renal function as specified in the study protocol Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 - Female patients 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 patients 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 - Peripheral neuropathy that is greater or equal to Grade 2 - Female patients who are lactating or pregnant - Major surgery or radiotherapy within 14 days before the first dose of study drug - Uncontrolled infection requiring systematic antibiotics within 14 days before the first dose of study drug - Diarrhea (> Grade 1) - Prior systemic therapy for multiple myeloma, including investigational drugs (prior treatment with corticosteroids or localized radiation therapy dose not disqualify the patient) - Systemic treatment with strong inhibitors of CYP1A2, strong inhibitors of CYP3A, or strong CYP3A inducers, or use of Ginko biloba or St. John's wort within 14 days before the first dose of study treatment - Central nervous system involvement - Diagnosis of smoldering multiple myeloma, Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome - Evidence of current uncontrolled cardiovascular conditions - Prior or concurrent deep vein thrombosis or pulmonary embolism - Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection - 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 the first dose 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

Additional Information

Official title An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Formulation of IXAZOMIB (MLN9708), Administered Twice-weekly in Combination With Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Requiring Systemic Treatment
Trial information was received from ClinicalTrials.gov and was last updated in June 2014.
Information provided to ClinicalTrials.gov by Millennium Pharmaceuticals, Inc..