Clinical Trial: Ixazomib (MLN9708) in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase 2 Study of Single-Agent MLN9708 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia With Mutated Nucleophosmin-1

Brief Summary: This phase 2 trial studies how well ixazomib(MLN9708) works in treating patients 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.

Detailed Summary:

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 patients 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:

Patients 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.


Sponsor: Bruno C. Medeiros

Current Primary Outcome: Overall Response Rate [ Time Frame: 9 weeks ]

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 patients with NPM1-mutated AML by LeukemiaNet1 guidelines:

CR is defined as either a full CR, or a CR with incomplete recovery. Although achievement of CR has unique clinical significance for improved overall survival and relapsed free survival compared to achievement of CR 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 pretreatment 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



Original Primary Outcome: Response rate, defined as the best of CR, CRi or PR assessed according to the LeukemiaNet guidelines [ Time Frame: Up to day 63 ]

The response rate will be accompanied by a two-sided 90% exact confidence interval.


Current Secondary Outcome: Overall Survival (OS) [ Time Frame: 1 year ]

Overall survival (OS) from time of study entry to the earlier of death from any cause or end of follow up at 1 year


Original Secondary Outcome:

  • Duration of response [ Time Frame: At 2 years ]
    Kaplan-Meier methods will be used to estimate duration of response.
  • Median overall survival [ Time Frame: Time of study entry to the earlier of death from any cause or end of follow up, assessed at 1 year ]
    Kaplan-Meier methods will be used to estimate duration of response.
  • Dose-limiting toxicities (DLT), defined as any grade 4 or select >= 3 non-hematologic toxicity graded according to the CTCAE version 4.0 [ Time Frame: Up to 2 years ]
  • Incidence of adverse events, graded according to the CTCAE version 4.0 [ Time Frame: Up to 2 years ]


Information By: Stanford University

Dates:
Date Received: November 25, 2013
Date Started: March 2014
Date Completion:
Last Updated: January 20, 2017
Last Verified: January 2017