This trial is active, not recruiting.

Condition light-chain amyloidosis
Treatment mln9708
Phase phase 1
Target proteasome
Sponsor Millennium Pharmaceuticals, Inc.
Start date May 2011
End date December 2013
Trial size 27 participants
Trial identifier NCT01318902, 2010-022497-13, C16007, U1111-1168-1192


This study will include patients with previously treated systemic relapsed or refractory light-chain (AL) amyloidosis who require further therapy and will be aimed at determining the safety profile and the maximum tolerated dose/recommended phase 2 dose of IXAZOMIB administered orally.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
Patients will receive escalating doses of MLN9708 orally on Days 1, 8 and 15 of a 28-day cycle. If there is no hematologic response after completion of 3 cycles, dexamethasone will be added on Days 1 to 4 of every cycle beginning with Cycle 4. If there is no hematologic response after the completion of 6 cycles, patients will discontinue therapy.

Primary Outcomes

Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: From start of study through 30 days after last dose or until initiation of subsequent antineoplastic therapy
Maximum Tolerated Dose and Recommended phase 2 dose of MLN9708
time frame: Dose Limiting Toxcities determined in Cycle 1 and adverse events monitored throughout the study will inform the recommended phase 2 dose

Secondary Outcomes

Whole blood 20S proteasome activity profile and inhibition parameters of multiple-dose oral MLN9708
time frame: Days 1,2,8,15,16,22
Number of patients with hematologic response rate during study period
time frame: Duration of treatment and then every 6 weeks thereafter until disease progression or initiation of subsequent antineoplastic therapy
Time to and duration of organ response and organ improvement
time frame: After cycles 3,6,9,12; every 6 months thereafter until disease progression or initiation of subsequent antineoplastic therapy
Time to hematologic and organ disease progression
time frame: Until evidence of hematologic and/or disease progression
Time from the date of the first dose of MLN9708 to the date of confirmed organ or hematologic disease progression, respectively
time frame: Every 6 weeks from end of treatment until disease progression or initiation of subsequent antineoplastic therapy
Patient survival probability at 1 year after the first dose of MLN9708
time frame: Every 12 weeks after progressive disease or initiation of subsequent antineoplastic therapy

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Male or female patients 18 years or older - Biopsy-proven systemic relapsed or refractory light-chain (AL) amyloidosis, which after at least 1 prior therapy, in the investigator's opinion, requires further treatment - If received stem cell transplant, must be at least 3 months posttransplantation and recovered from side effects - Must have measurable disease defined as serum differential free light chain concentration ≥ 40mg/L - Must have objective measurable organ (heart or kidney) amyloid involvement - Must have cardiac biomarker risk stage I or II disease - Must have adequate hematologic, hepatic, and renal function - 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 - 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 - Cardiac status as described in protocol - Severe diarrhea (≥ Grade 3) not controllable with medication or requires administration of total parenteral nutrition - Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of MLN9708 - Uncontrolled infection requiring systematic antibiotics - Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection - Presence of other active malignancy with the exception of nonmelanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate-specific antigen is within normal limit, or any completely resected carcinoma in situ - Female patients who are lactating or pregnant - Major surgery within 14 days before the first dose of study drug - 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 Study of the Oral Formulation of IXAZOMIB (MLN9708) Administered Weekly in Adult Patients With Relapsed or Refractory Light-Chain Amyloidosis Who Require Further Treatment
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Millennium Pharmaceuticals, Inc..