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

Browse trials for

• Graft vs Host Disease 806

Keywords

• Cyclophosphamide toxicities
• Cyclophosphamide dose reduction
• Graft-Versus-Host Disease: GVHD
• Hematopoietic stem cell transplantation

Graft vs Host Disease

806 studies on the registry are indexed under Graft vs Host Disease; 138 are open to participants now.

This study's planned enrollment of 180 is above the median of 35 across 637 interventional studies indexed under Graft vs Host Disease.

Lead sponsor

Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.

Study arms

• Experimental
  Reduced dose

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

  Drug: Cyclophosphamide 35mg/kg/day

• Active comparator
  Standard dose

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

  Drug: Cyclophosphamide 50mg/kg/day

Interventions

• DrugCyclophosphamide 35mg/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).

• DrugCyclophosphamide 50mg/kg/day

  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).

Primary outcomes

1. GVHD-free, relapse-free, event-free survival (GREFS)

   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

   Time frame: 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

Secondary outcomes

1. Overall survival (OS)

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

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

2. Quality of life FACT-BMT

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

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

3. Quality of life EQ-5D-5L

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

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

4. Toxicities, infection and hematogical recovery

   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

   Time frame: 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

5. Cumulative incidence and severity of acute and chronic GVHD assessed according to the 2014 NIH criteria

   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

   Time frame: 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

6. Non-relapse mortality

   Time frame: 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.

7. Cumulative incidence of relapse

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

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

8. Disease-free survival (DFS)

   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

   Time frame: At two years

9. GVHD-free, relapse-free survival (GRFS)

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

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

10. Cost-effectiveness

    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.

    Time frame: From transplantation until 2 years

11. Cytokine profiles

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

    Time frame: Inclusion, Day 0, Day 15-35, Day 90, Day 365

12. Gut microbiota

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

    Time frame: Inclusion, Day 0, Day 15-35, Day 90

Individual participant data

Plan to share: No