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NCT Number: NCT07193420

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

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.

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Key information

Conditions

GVHD - Graft-Versus-Host Disease Graft vs Host Disease HSCT Haploidentical Stem Cell Transplantation Immune System Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Cyclophosphamide 35mg/kg/day

Drug

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 50mg/kg/day

Drug

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)

    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

    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

Secondary outcomes

  1. Overall survival (OS)

    Time frame: 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

  2. Quality of life FACT-BMT

    Time frame: 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)

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

    Time frame: 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).

  4. Toxicities, infection and hematogical recovery

    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

    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

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

    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

  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

    Time frame: 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

  8. Disease-free survival (DFS)

    Time frame: 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

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

    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

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

  10. Cost-effectiveness

    Time frame: 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.

  11. Cytokine profiles

    Time frame: 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

  12. Gut microbiota

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

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

Study contacts

Contact information is provided by the study sponsor or research team.

Mohamad MOHTY, PU-PH

CONTACT

[email protected]

00 33 1.49.28.26.20

Remy DULERY

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

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

Acronym: REDUCy

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Sep 25, 2025
Registry last updated
May 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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