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

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.

cyclophosphamide administered at 35mg/kg/day (Adjusted body weight) on days +3 and +4

Drug: Cyclophosphamide 35mg/kg/day

cyclophosphamide administered at 50mg/kg/day (Adjusted Body Weight) on days +3 and +4

Drug: Cyclophosphamide 50mg/kg/day

Cyclophosphamide will be administered intravenously (IV) post-HSCT at the experimental dose (70 mg/kg, divided into two doses of 35 mg/kg/day (Adjusted Body Weight) on days +3 and +4).

Cyclophosphamide will be administered intravenously (IV) post-HSCT at the standard dose (100 mg/kg, divided into two doses of 50 mg/kg/day (Adjusted Body Weight) on days +3 and +4).

Plazo: Day 0 to first occurrence of acute grade III-IV GVHD, severe chronic GVHD, relapse, death, grade 3-4 cardiac event, or grade 3-4 BK virus-associated HC (up to 24 months post-transplant); platelet recovery (>50 × 10^9/L) assessed until Day +60

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

Plazo: From transplantation until death from any cause or up to 24 months, whichever occurs first

Overall survival (OS) at 2 years is defined as survival irrespective of disease status

Plazo: At 1, 3, 6, 12, and 24 months after HSCT

Quality of life compared to baseline using questionnaire: FACT-BMT (Functional Assessment of Cancer Therapy - Bone Marrow Transplant, version 4)

Plazo: At 1, 3, 6, 12, and 24 months after HSCT

Quality of life compared to baseline using questionnaire: EQ-5D-5L (EuroQol 5-Dimension, 5-Level questionnaire).

Plazo: From transplantation until the occurrence of the event, day +60 for hematological recovery, or up to 24 months for organ damage toxicities and infections, whichever occurs first

Organ damage toxicities assessed by the common terminology criteria for adverse events (CTCAE) v5.0, cumulative incidences of bacterial, viral, and fungal infections, and failure to achieve neutrophil recovery (absolute neutrophil count \> 0.5 x 10\^9/L) or platelet recovery (platelet count \> 50 x 10\^9/L) after HSCT

Plazo: From transplantation until the occurrence of GVHD or death from any cause, or up to 180 days after transplantation for acute GVHD, or up to 24 months for chronic GVHD, whichever occurs first

Acute GVHD grading should be performed by the MAGIC criteria, for chronic GVHD; the time of onset of chronic GVHD will be recorded, as well as the requirement for a systemic immunosuppressive therapy and the maximum grade achieved according to the NIH Consensus Criteria

Plazo: From transplantation until death without evidence of relapse or up to 24 months, whichever occurs first Description: NRM refers to death without evidence of disease relapse.

No informado en este registro.

Plazo: From transplantation until the occurrence of relapse or up to 24 months, whichever occurs first

Cumulative incidence functions (CIFs) will estimate outcomes such as relapse

Plazo: At two years

DFS is defined as survival without relapse or progression, the endpoints will be censored at two years to address differences in follow-up between groups

Plazo: From transplantation until the occurrence of acute grade III-IV GVHD, severe chronic GVHD, relapse, death, or up to 24 months, whichever occurs first

GRFS encompasses survival free from acute grade III-IV GVHD, chronic GVHD requiring systemic immunosuppression, or relapse

Plazo: From transplantation until 2 years

The endpoint of the medico-economic analysis is the incremental cost-utility ratio (ICUR) at 24 months of reducing the total dose of PTCy to 70 mg/kg on GREFS compared to the standard dose of 100 mg/kg. The incremental cost-utility ratio will be calculated in cost per QALY gained.

The secondary endpoint is the incremental cost-effectiveness ratio (ICER) at 24 months. The incremental cost-effectiveness ratio will be calculated in cost per life-years gained.

Plazo: Inclusion, Day 0, Day 15-35, Day 90, Day 365

This ancillary study will evaluate cytokine profiles in relation to PTCy doses using a multiplex test based on fluorescence-coded beads

Plazo: Inclusion, Day 0, Day 15-35, Day 90

This ancillary study will evaluate gut microbiota: richness based on α-diversity indexes

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