Phase 2 study of interferon-gamma and donor lymphocyte infusion for the treatment of relapsed myeloid malignancies after allogeneic stem cell transplantation
Active Project Grant Awarded Last action
- Award ID
- R01FD008187
- Recipient
-
University Of Pittsburgh - Of The Commonwealth System Of Higher Education UEI MKAGLD59JRL1
- Awarding agency
-
FDA Office of Acquisition and Grant Services
Food and Drug Administration, Department of Health and Human Services
- Obligated
- $882,247
Award facts
- Assistance listing
- 93.103 Food and Drug Administration Research
- Completion date 44% complete
- Originally
- Funding agency
- Office of Medical Products and Tobacco Food and Drug Administration, Department of Health and Human Services
- Place of performance
- Pennsylvania, USA
Award details come from USAspending.gov.
Description
- Abstract
- Allogeneic stem cell transplantation (ALLOSCT) is a potentially curative therapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Donor-derived alloreactive T cells can kill recipient leukemia cells, mediating the graft-VS-leukemia effect (GVL). GVL failure leads to post- transplant relapse, affecting 30-40% of ALLOSCT recipients and leading to extremely poor prognosis, with a median survival of 6 months. The clinical sensitivity of leukemias to GVL varies by disease type. DR. Shlomchik, CO-PI, sought the mechanism of GVL resistance using preclinical GVL models and discovered that myeloblastic leukemia required the expression of the IFN-Γ receptor for GVL. Two independent groups reported lower levels of human leukocyte antigen (HLA) expression in myeloid blasts post-transplant relapse, which IFN-Γ can restore in vitro. These data supported conducting a phase 1 trial to evaluate the safety of IFN-Γ (actimmune®) in AML/MDS patients with post-transplant relapse (NCT04628338). 4 out of 6 patients who received IFN-Γ and subsequent donor leukocyte infusion (DLI) achieved durable complete remissions with full donor hematopoiesis recovery. Given these favorable results, we propose a multicenter phase 2 trial to evaluate the efficacy of IFN-Γ/DLI compared to the outcomes in a synthetic control generated from the center for international blood and marrow transplant research (CIBMTR) database. Patients with AML/MDS who developed relapse with >5% bone marrow myeloblasts after an HLA-matched ALLOSCT will be eligible. Subjects will receive 100MCG of IFN-Γ thrice weekly by self-subcutaneous injection for four weeks. If IFN-Γ is tolerated, subjects will receive DLI concurrently with IFN-Γ for eight more weeks to complete the 12-week treatment intervention. The primary objective is to evaluate the efficacy of IFN-Γ/DLI, measured by event-free survival at 1 year. The secondary objectives are to evaluate the safety and efficacy of IFN-Γ/DLI measured by secondary endpoints, including measurable disease- negative complete remission at 6 months and overall survival at 12 months. The incidence of steroid and ruxolitinib-refractory graft-versus-host disease will be used for the stopping rule. 45 participants will be enrolled to receive IFN-Γ/DLI. The major clinical endpoints will be compared to 3 CIBMTR synthetic cohorts of patients treated with 1) chemotherapy only, 2) chemotherapy+ DLI, or 3) DLI only. Each control group will have 135 subjects (1:3 ratio of treated subjects). In exploratory studies, we will analyze IFN-Γ induced transcriptomic changes in leukemic and immune cells to find the biomarkers that could be used to select subjects for future studies.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $0 | |
| Original award | $882,247 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The Medical College Of Wisconsin, Inc. | $175,951 | |
| Fred Hutchinson Cancer Center | $417,394 | |
| The Washington University | $260,589 | |
| Fred Hutchinson Cancer Center | $264,341 | |
| The Medical College Of Wisconsin, Inc. | $58,651 |
Quick answers
Who received award R01FD008187?
R01FD008187 was awarded to University Of Pittsburgh - Of The Commonwealth System Of Higher Education by FDA Office of Acquisition and Grant Services (Food and Drug Administration) on September 15, 2024.
How much is award R01FD008187 worth?
$882,247 has been obligated on R01FD008187.
Which agency awarded R01FD008187?
FDA Office of Acquisition and Grant Services (Food and Drug Administration) awarded R01FD008187, with funding from Office of Medical Products and Tobacco (Food and Drug Administration).
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