GVHD Prophylaxis With Methotrexate in Haploidentical HCT Using Posttransplant Cyclophosphamide

Last updated: September 10, 2021
Sponsor: University of Sao Paulo General Hospital
Overall Status: Active - Recruiting

Phase

1/2

Condition

Hematologic Neoplasms

Blood Cancer

Treatment

N/A

Clinical Study ID

NCT04622956
30802020.7.1001.0068
  • Ages 18-70
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Diagnosis of acute myeloid leukemia and chronic myeloid leukemia in completemorphologic remission, myelodysplastic syndrome with less than 10% in bone marrow orperipheral blood, Ph-negative acute lymphoblastic leukemia in complete morphologicremission, chemosensitive Hodgkin lymphoma or non-Hodgkin lymphoma in at least partialremission
  • Donor type: haploidentical related donor
  • Graft source: bone marrow or peripheral blood
  • Recipients of non-myeloblative or myeloablative intensity conditioning
  • Left Ventricle Ejection fraction > 40%
  • Estimated creatinine clearance > 40 mL/min
  • Adjusted DLCO ≥ 40% and FEV1 ≥ 40%
  • Total bilirubin < 2x ULN e ALT/AST < 2.5x ULN

Exclusion

Exclusion Criteria:

  • Prior allogeneic transplant
  • Ex-vivo graft manipulation (T-cell-depleted or CD34-selected grafts)
  • Use of alemtuzumab or anti-thymocyte globulin
  • KPS < 70%
  • Patients with uncontrolled bacterial, viral or fungal infections (currently takingmedication and with progression or no clinical improvement) at time of enrollment
  • Pregnant or lactating women
  • Patients seropositive for human immunodeficiency virus (HIV) or active hepatitis B orC infection by PCR
  • Presence of fluid collection (ascites, pleural or pericardial effusion) that mayinterfere with methotrexate clearance or make methotrexate use contraindicated
  • Patients with a serious medical or psychiatric illness likely to interfere withparticipation in this study

Study Design

Total Participants: 47
Study Start date:
October 07, 2020
Estimated Completion Date:
December 31, 2025

Connect with a study center

  • Instituto Nacional de Câncer José Alencar Gomes Da Silva - Inca

    Rio De Janeiro, RJ
    Brazil

    Active - Recruiting

  • Centro de Hematologia e Hemoterapia - HEMOCENTRO

    Campinas, São Paulo
    Brazil

    Active - Recruiting

  • Hospital Amaral Carvalho / Fundação Dr. Amaral Carvalho

    Jaú, São Paulo
    Brazil

    Active - Recruiting

  • Hospital das Clinicas da Universidade de Sao Paulo

    Sao Paulo, 05403-000
    Brazil

    Active - Recruiting

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