Reduced Post-transplant Cyclophosphamide Dose in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation for Hematological Malignancies

Reduced Post-transplant Cyclophosphamide Dose in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation for Hematological Malignancies: a Phase III Randomized Study

Phase III comparative, open-label, randomized (1:1) trial designed to evaluate the efficacy of reducing the total dose of PTCy to 70 mg/kg on GREFS compared to the standard dose of 100 mg/kg, in patients undergoing haploidentical HSCT for the treatment of a hematological malignancy, two years after HSCT.

The primary endpoint is the assessment of the GREFS at 2 years after HSCT, a composite endpoint defined as the probability of survival without severe GVHD, relapse/progression of the hematological malignancy, or PTCy-associated adverse event, whichever comes first from transplantation.

Inclusion Criteria:

• Age ≥ 18 years
• Confirmed hematological malignancy with an indication for allogeneic HSCT
• Presence of a haploidentical donor willing to donate PBSC
• Patient planned to receive a thiotepa-based conditioning regimen
• Provision of written informed consent Affiliation to a social security system (excluding "Aide Médicale d'État")

Exclusion Criteria:

• Karnofsky performance status < 70%

• Life expectancy < 1 month, as determined by the attending physician

• Acute or chronic heart failure, defined as left ventricular ejection fraction < 40%

• Pulmonary dysfunction with diffusion capacity < 50% of predicted values

• Renal impairment with estimated glomerular filtration rate (eGFR) < 45 mL/min (calculated using the CKD-EPI formula)

• Decompensated hemolytic anemia

• Fanconi anemia and other DNA breakage repair disorders

• Acute urothelial toxicity due to cytotoxic chemotherapy or radiotherapy

• Obstruction of urinary outflow

• Concomitant use with yellow fever vaccine and with live virus and bacterial vaccines

• Combination with products containing Hypericum perforatum

• Combination with medicines that are substrates for the multidrug efflux transporter P-glycoprotein (P-gp) or the organic anion transporter proteins (OATP) and for which elevated plasma concentrations are associated with serious and/or life-threatening events, e.g., bosentan, dabigatran etexilate and aliskiren

• Active non-controlled infectious disease

• Positive HIV status

• Pregnancy, breast-feeding, or refusal to use effective contraception for the duration of the study and 6 months after the last treatment dose

• Individuals under legal protection measures or unable to provide consent (e.g., severe neurological or psychiatric disorders, or deprivation of liberty by judicial or administrative decision)

• Hypersensitivity to the active substance or any of the excipients

• Concurrent participation in another investigational therapeutic study

• Inability to comply with study procedures as assessed by the investigator based on objective criteria, including but not limited to:

  • Significant language barrier in the absence of adequate translation support
  • Social or geographic situation preventing follow-up and adherence to visit schedule
  • Ongoing substance abuse likely to interfere with protocol compliance
  • Documented cognitive or functional impairment not otherwise covered under legal protection