NCT02250300

MLN9708 for the Prophylaxis of Chronic Graft-versus-host Disease in Patient Undergoing Allogeneic Transplantation

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 68 (actual)
• Sponsor: Mehdi Hamadani · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase I/II study of MLN9708 for the prophylaxis of chronic graft-versus-host-disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). During the phase I portion, patients undergoing both sibling and unrelated donor transplantation will be enrolled on the same arm to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD). During the phase II portion of the trial, patients will be enrolled into two separate and independent cohorts: a) Matched sibling transplants and b) Unrelated donors transplants. Both cohorts will be enrolled and analyzed separately.

Detailed description

* For potential candidates for this trial, the recommended acute GVHD prophylaxis is a tacrolimus, methotrexate and atorvastatin combination. However, any acute GVHD prophylaxis regimen at the discretion of treating physician (not involving in vivo or ex vivo T-cell depletion, cluster of differentiation 34 (CD34) + cell selection, or post-HCT cyclophosphamide) will be permitted. * During the phase I portion for chronic GVHD prophylaxis, four doses of MLN9708 will be administered orally (to patients undergoing either matched sibling or unrelated donor transplantation) on days 1, 8, 15 and 22, starting on day +60 to +74 post allogeneic HCT. If zero of three patients experienced DLT at dose level 2, then it would be considered a MTD. If two or more patients experienced a DLT, dose escalation would halt and the dose level would be expanded to six patients to determine the MTD. If the dose level below already has six patients, enrolled, then it will be considered the MTD. If two or more patients experience DLT on first dose level (i.e., dose level 1), then, patients will be enrolled on dose level -1. No intrapatient dose escalation will be permitted. * MTD is defined at maximum dose level with fewer than two of six patients experiencing DLT. * The phase II portion will utilize the MTD for MLN9708, determined from phase I portion of the study. In phase II, patients will be enrolled in two independent cohorts of matched sibling and matched unrelated donor transplants. * During the phase II portion, for chronic GVHD prophylaxis, four doses of MLN9708 will be administered orally on days 1, 8, 15 and 22, starting on day +60 to +90 post allogeneic HCT.

Conditions

• Allogeneic Hematopoietic Stem Cell Transplantation

Interventions

Type	Name	Description
DRUG	MLN9708 (2.3 mg)	2.3 mg
DRUG	MLN9708 (4.0 mg)	4.0 mg
DRUG	MLN9708 (3.0 mg)	3.0 mg

Timeline

• Start date: 2014-11-19
• Primary completion: 2020-10-06
• Completion: 2020-10-06
• First posted: 2014-09-26
• Last updated: 2023-03-08
• Results posted: 2023-03-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study