This phase 2 trial studies how well ixazomib(MLN9708) works in treating study participants with relapsed or refractory acute myeloid leukemia. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVE: Determine the best response including complete remission (CR), CR with incomplete recovery (CRi), and partial remission (PR) after 3 cycles of treatment with MLN9708 (ixazomib) in participants with nucleophosmin (NPM)1-mutated acute myeloid leukemia (AML) (following the LeukemiaNet1 guidelines for response criteria). SECONDARY OBJECTIVES: * Determine the duration of remission in all responders after treatment with MLN9708 defined as the time of documented remission until relapse. * Determine the 1 year overall survival, which will be measured from time of study entry to the earlier of death from any cause or end of follow up at 1 year. * Establish toxicity and tolerability of MLN9708 treatment in AML, including non-hematologic toxicities grade 3 or above as specified by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. OUTLINE: Participants receive ixazomib orally (PO) on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
4
Given orally (PO)
Stanford University Cancer Institute
Stanford, California, United States
Overall Response Rate (ORR)
Overall response rate after 3 cycles of treatment (9 weeks) was assessed as complete remission (CR); CR with incomplete recovery (CRi); and partial remission (PR) with MLN9708, in participants with NPM1-mutated AML by LeukemiaNet1 guidelines: Although achievement of complete remission (CR) has unique clinical significance for improved overall survival (OS) and relapse-free survival (RFS) compared to achievement of CRi with incomplete platelet recovery, the latter is still a clinically meaningful response, as it is independently-superior to resistant disease. Partial remission (PR) is defined as meeting all hematologic criteria for CR with an allowance for 5% to 25% bone marrow blasts or decrease of pre-treatment bone marrow blast percentage by at least 50%. Stable disease is defined as a change in bone marrow aspirate blast count within 10% of baseline. Relapsed disease is defined as reappearance of blasts in the blood or bone marrow blasts
Time frame: 9 weeks
Duration of Response (DOR)
Duration of response (DOR) in participants with complete remission (CR) was defined as the period of time from documented complete remission through relapse or death, with relapse defined as reappearance of blasts in the blood or bone marrow blasts, after documented CR. DOR was to be assessed through at least 1 year follow-up.
Time frame: 1 year
Overall Survival (OS)
Overall survival (OS) from time of study entry to the earlier of death from any cause or end of follow up at 1 year
Time frame: 1 year
Serious Adverse Events Related to Ixazomib
Ixazomib toxicity and tolerability were assessed based on the non-hematologic toxicities ≥ Grade 3 determined to be possibly, probably, or definitely related to the study agent Ixazomib. Adverse events that are possibly, probably, or definitely related to the study agent are considered "toxicities." The outcome is reported as the overall number of non-hematologic toxicities ≥ Grade 3.
Time frame: 1 year
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