Clinical Trial: Open-label, Phase II Study of MLN9708 in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Open-label, Single-center Phase II Study of MLN9708 (Ixazomib) in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas

Brief Summary:

Historically cutaneous and peripheral T-cell lymphomas have response rates of approximately 30% to standard chemotherapy regimens. We alternatively hypothesize that MLN9708 will be active in this disease and will improve best objective response.

We will also determine the extent to which MLN9708 inhibits GATA-3 (Trans-acting T-cell-specific transcription factor) expression, which is associated with poor prognosis, and whether GATA-3 expression represents a novel predictive biomarker for MLN9708 sensitivity.


Detailed Summary: Up to 25 patients meeting the inclusion and exclusion criteria will be enrolled into this trial in two stages. All enrolled patients will be treated with MLN9708 4 mg PO weekly (days 1, 8, 15 every 28 days) until disease progression or unacceptable toxicity. In the initial stage of the study a total of 11 patients will be enrolled and treated with MLN9708. Should at least 4 patients exhibit a response (CR/CRu, PR), the second stage of 14 patients will open for enrollment. Efficacy will be assessed radiographically, by peripheral blood and bone marrow examination (when indicated), and physical exam every 8 weeks. Safety will be assessed by periodic physical exams, laboratory studies, and adverse events. All patients will have a follow-up visit 35 days (+/-7 days) following the last study drug treatment. Patients with accessible tumor tissue will be asked to undergo a biopsy for a fresh tissue sample for assessment of GATA-3 expression. Archived tissue samples from the initial diagnostic biopsy and the most recent lymphoma biopsy will be obtained in the event a fresh tumor biopsy cannot be obtained. Patients with GATA-3+ TCL and accessible tumor tissue will undergo a tumor biopsy at day 21 (+/- 7 days) of cycle 1. All baseline fresh or archived tissue will undergo central pathology review to confirm the diagnosis of TCL. The rationale for proteasome inhibition in T-cell lymphomas, based on the pre-clinical (and previous phase II) data, is compelling. Therefore, this phase II study will not be restricted to patients with GATA-3 expressing lymphomas.
Sponsor: University of Michigan Cancer Center

Current Primary Outcome: Objective Response Rate [ Time Frame: 24 months after initiation of study treatment ]

Objective response is considered CR (Complete Response), CRu (Complete Response Unknown), or PR (Partial Response) and will be measured after every 2nd cycle of treatment until the 6th cycle, then every 3 months until 24 months, then every 6 months, all until disease progression or death. All patients receiving any MLN9708 therapy per protocol are considered evaluable for the primary endpoint; however, patients not able to receive at least 2-cycles of MLN9708 with an accompanying response assessment will be considered treatment failures.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of Adverse Events, Grades 3-5 [ Time Frame: 30 days after the last dose of study drug ]
    To assess the safety and tolerability of MLN9708, the incidence of Adverse Events (AEs), as well as severity, seriousness and relatedness will be recorded.
  • Progression Free Survival Time [ Time Frame: 24 months after initiation of study treatment ]
    Time from study start until disease progression or death.
  • Overall Survival Time [ Time Frame: 24 months after initiation of study treatment ]
    Time from study start until death.
  • Duration of Response [ Time Frame: 24 months after initiation of study treatment ]
    Time from documentation of tumor response to disease progression.


Original Secondary Outcome: Same as current

Information By: University of Michigan Cancer Center

Dates:
Date Received: June 5, 2014
Date Started: September 2014
Date Completion:
Last Updated: December 15, 2016
Last Verified: December 2016