NCT02158975

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: University of Michigan Rogel Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 description

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.

Conditions

• Lymphoma, T-Cell

Interventions

Type	Name	Description
DRUG	MLN9708

Timeline

• Start date: 2014-09-01
• Primary completion: 2016-10-01
• Completion: 2016-11-01
• First posted: 2014-06-09
• Last updated: 2017-11-13
• Results posted: 2017-11-13

Locations

1 site across 1 country: United States