NCT04622956

GVHD Prophylaxis With Methotrexate in Haploidentical HCT Using Posttransplant Cyclophosphamide

GVHD Prophylaxis With Methotrexate and Cyclosporine in Haploidentical Stem Cell Transplantation Using Posttransplant Cyclophosphamide in Hematologic Malignancies: Phase I/II Trial

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 47 (estimated)
• Sponsor: University of Sao Paulo General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Allogeneic hematopoietic cell transplantation (HCT) is an important therapeutic strategy for many malignant and benign hematologic diseases. Haploidentical HCT has been increasingly used in patients lacking a HLA-matched donor due to its prompt availability, possibly lower cost and results comparable with other donor types. Graft-versus-host disease (GVHD) is the main cause of morbidity and mortality after HSCT, and prophylactic strategies are routinely used. In the context of haploidentical HCT, posttransplant cyclophosphamide plus cyclosporine and mycophenolate mofetil (MMF) is the most common platform used in Brazil. Data comparing MMF and methotrexate (MTX) as GVHD prophylaxes have proved controversial in other donor types, yet some large studies have showed that MTX is associated with lower risk of GVHD and improved long-term outcomes. Moreover, it is known that MMF is a potent inhibitor of natural killer (NK) cells, possibly interfering with the graft-versus-leukemia effect in haploidentical HCT. Given the possible advantages and the absence of consistent evidence regarding safety, efficacy and ideal dosage of MTX as GVHD prophylaxis in this setting, we propose a phase I / II study evaluating this drug in adult patients with hematologic malignancies undergoing haploidentical HCT with posttransplant cyclophosphamide.

Conditions

• Graft Vs Host Disease
• Hematopoietic Neoplasm

Interventions

Type	Name	Description
DRUG	Methotrexate Injectable Solution	Phase 1: * Level -1: Methotrexate 7.5 mg/m2 on D+6 and D+9\*. Level -1 will be explored only if the starting dose is too toxic (reduced dose). * Level 0 \[Starting Dose\]: Methotrexate 10 mg/m2 on D+6 and 7.5 mg/m2 on D+9 * Level +1: Methotrexate 10 mg/m2 on D+6 and D+9 * Level +2: Methotrexate 15 mg/m2 on D+6 and 10 mg/m2 on D+9 Phase 2: dose determined in the phase 1 trial

Timeline

• Start date: 2020-10-07
• Primary completion: 2023-12-01
• Completion: 2025-12-01
• First posted: 2020-11-10
• Last updated: 2021-09-14

Locations

4 sites across 1 country: Brazil