Overview

This trial is active, not recruiting.

Condition multiple myeloma
Treatments ixazomib, melphalan 9 mg/m2, melphalan 6 mg/m2, prednisone
Phase phase 1/phase 2
Target proteasome
Sponsor Millennium Pharmaceuticals, Inc.
Start date June 2011
End date December 2016
Trial size 164 participants
Trial identifier NCT01335685, 2010-023772-71, C16006

Summary

This will be a phase 1/2, multicenter, 2-arm, open-label study using the oral formulation of IXAZOMIB when added to standard melphalan and prednisone (MP) treatment. Both phases of the study will include patients who have newly diagnosed multiple myeloma and are ineligible for high-dose therapy plus stem cell transplantation because of age (≥65 years of age) or coexisting conditions and for whom standard MP treatment is indicated.

Note: Phase 2 of the trial will be randomized.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Phase 1 only. Induction: IXAZOMIB on days 1, 4, 8, 11, 22, 25, 29, 32. Melphalan 9 mg/m2 and Prednisone on days 1-4. Repeat every 42 days for 9 cycles. Maintenance: IXAZOMIB only on days 1, 8, 15 in 28-day cycle.
ixazomib
melphalan 9 mg/m2
prednisone
60 mg/m2
(Experimental)
Phases 1 and 2. Induction: IXAZOMIB on days 1, 8, 15. Melphalan 6 mg/m2 and Prednisone on days 1-4. Repeat every 28 days for 13 cycles. Maintenance: IXAZOMIB only on days 1, 8, 15 in 28-day cycle.
ixazomib
melphalan 6 mg/m2
prednisone
60 mg/m2
(Experimental)
Phases 1 and 2 Induction: IXAZOMIB on days 1, 8, 15, 22, 29. Melphalan 9 mg/m2 and Prednisone on days 1-4. Repeat every 42 days for 9 cycles. Maintenance: IXAZOMIB only on days 1, 8, 15 in 28-day cycle. Phase 2 will include either Arm C or Arm D based on the safety, tolerability and efficacy observed in Phase 1.
ixazomib
melphalan 9 mg/m2
prednisone
60 mg/m2
(Experimental)
Phases 1 and 2 Induction: IXAZOMIB on days 1, 8, 22, 29. Melphalan 9 mg/m2 and Prednisone on days 1-4. Repeat every 42 days for 9 cycles. Maintenance: IXAZOMIB only on days 1, 8, 15 in 28-day cycle. Phase 2 will include either Arm C or Arm D based on the safety, tolerability and efficacy observed in Phase 1.
ixazomib
melphalan 9 mg/m2
prednisone
60 mg/m2

Primary Outcomes

Measure
Maximum Tolerated Dose and Recommended phase 2 dose of IXAZOMIB (phase 1)
time frame: Dose Limiting Toxicities determined in Cycle 1 and adverse events monitored throughout the study will inform the recommended phase 2 dose, approximately 2 years
Number of patients with a complete response and very good partial response (phase 2)
time frame: During the induction period, approximately 1 year

Secondary Outcomes

Measure
Maximum inhibition (Emax) and time of occurrence of Emax (TEmax) (phase 1)
time frame: At multiple time points during cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 days depending on the arm of the study
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 during cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 days depending on the arm of the study
Number of patients with response, including Complete Response, Very Good Partial Response and Partial Response (phase 1 and 2)
time frame: Duration of treatment and then every 12 weeks thereafter until disease progression or initiation of subsequent antineoplastic therapy, expected duration approximately 4 years
Time to response (phase 2)
time frame: From the date of enrollment to the date of the first documented response during the induction period, expected average of up to 1 year
Duration of response (phase 2)
time frame: From the date of first response to the date of disease progression, approximately 4 years
Time to progression (phase 2)
time frame: From date of enrollment to the date of first documented disease progression, approximately 4 years
Time to next therapy (phase 2)
time frame: From the date of enrollment to the date of subsequent antineoplastic therapy, approximately 4 years
Number of patients with progression free survival (phase 2)
time frame: From the date of enrollment to the date of first documented disease progression or death, approximately 4 years
Number of patients with overall survival (phase 2)
time frame: From date of enrollment to date of death, approximately 4 years
Number of all adverse events (phase 2)
time frame: From first dose of study drug through 30 days after last dose of study drug or until the start of subsequent antineoplastic therapy, approximately 2 years and 30 days
Assessments of Quality of Life (phase 2)
time frame: At screening, Day 1 of each treatment cycle, and Days 1 and 15 of each maintenance cycle, approximately 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Male or female patient for whom standard melphalan prednisone (MP) treatment is indicated and who is not a candidate for high-dose therapy plus stem cell transplantation (HDT-SCT) for 1 of the following reasons: the patient is 65 years of age or older OR the patient is less than 65 years of age but has significant comorbid condition(s) that are likely to have a negative impact on tolerability of HDT-SCT - Symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage diagnosed according to standard criteria - Measurable disease as specified in study protocol - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 - Must have adequate hematologic, liver, and renal function - Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse - Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse - 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 - 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) - Central nervous system involvement - Cardiac status as described in protocol - Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of IXAZOMIB - Diagnosis of smoldering multiple myeloma, Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome - Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection - 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 - Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol

Additional Information

Official title An Open-Label, Dose-Escalation, Phase 1/2 Study of the Oral Form of IXAZOMIB (MLN9708), a Next-Generation Proteasome Inhibitor, Administered in Combination With a Standard Care Regimen of Melphalan and Prednisone in Patients With Newly Diagnosed Multiple Myeloma Requiring Systemic Treatment
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Takeda.