GVHD - Graft-Versus-Host DiseasePhase 3REDUCyNCT07193420
Reduced Post-transplant Cyclophosphamide Dose in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation for Hematological Malignancies
A Phase 3 study testing Cyclophosphamide 35mg/kg/day and Cyclophosphamide 50mg/kg/day in people with GVHD - Graft-Versus-Host Disease and HSCT, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GVHD - Graft-Versus-Host Disease, HSCT, Haploidentical Stem Cell Transplantation
- What is being tested?
- Cyclophosphamide 35mg/kg/day and Cyclophosphamide 50mg/kg/day
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2026to Jun 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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")
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Remy DULERY contact
France1 site
Saint Antoine Hospital - Hematology Department
Paris, 75012
Florent MALARD, PU-PH, 00 33 1.49.28.26.20, malardf@yahoo.fr
Remy DULERY, remy.dulery@aphp.fr
About this study
Official title: 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.
Read the detailed description
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.
- Being tested
- Cyclophosphamide 35mg/kg/day, Cyclophosphamide 50mg/kg/day
- Keywords
- Cyclophosphamide toxicities, Cyclophosphamide dose reduction, Graft-Versus-Host Disease: GVHD, Hematopoietic stem cell transplantation
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide 35mg/kg/dayDrug
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/dayDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Reduced dose | Experimental | cyclophosphamide administered at 35mg/kg/day (Adjusted body weight) on days +3 and +4 Receives: Drug: Cyclophosphamide 35mg/kg/day |
| Standard dose | Active comparator | cyclophosphamide administered at 50mg/kg/day (Adjusted Body Weight) on days +3 and +4 Receives: Drug: Cyclophosphamide 50mg/kg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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 (12)
Overall survival (OS)
Overall survival (OS) at 2 years is defined as survival irrespective of disease status
Measured: From transplantation until death from any cause or up to 24 months, whichever occurs first
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)
Measured: At 1, 3, 6, 12, and 24 months after HSCT
Quality of life EQ-5D-5L
Quality of life compared to baseline using questionnaire: EQ-5D-5L (EuroQol 5-Dimension, 5-Level questionnaire).
Measured: At 1, 3, 6, 12, and 24 months after HSCT
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
Measured: 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
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
Measured: 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
Non-relapse mortality
Measured: 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.
Cumulative incidence of relapse
Cumulative incidence functions (CIFs) will estimate outcomes such as relapse
Measured: From transplantation until the occurrence of relapse or up to 24 months, whichever occurs first
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
Measured: At two years
GVHD-free, relapse-free survival (GRFS)
GRFS encompasses survival free from acute grade III-IV GVHD, chronic GVHD requiring systemic immunosuppression, or relapse
Measured: From transplantation until the occurrence of acute grade III-IV GVHD, severe chronic GVHD, relapse, death, or up to 24 months, whichever occurs first
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.
Measured: From transplantation until 2 years
Cytokine profiles
This ancillary study will evaluate cytokine profiles in relation to PTCy doses using a multiplex test based on fluorescence-coded beads
Measured: Inclusion, Day 0, Day 15-35, Day 90, Day 365
Gut microbiota
This ancillary study will evaluate gut microbiota: richness based on α-diversity indexes
Measured: Inclusion, Day 0, Day 15-35, Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2025
- Study startJun 2026 (estimated)
- Primary completionJun 2030 (estimated)
- Study completionJun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GVHD - Graft-Versus-Host DiseaseStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The randomization will be stratified by age (\< 60 years versus ≥ 60 years), disease risk index (low and intermediate versus high and very-high), and antithymocyte globulin use (yes versus no).
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mohamad MOHTY, PU-PH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07193420
- Sponsor's protocol ID
- APHP241012
- Other IDs
- 2024-519986-23-00
- Acronym
- REDUCy
- Status last verified
- May 2026
- First submitted
- 11 Jul 2025
- Last updated
- 12 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced Post-transplant Cyclophosphamide Dose in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation for Hematological Malignancies: a Phase III Randomized Study
- ClinicalTrials.gov ID
- NCT07193420
- Acronym / sponsor ID
- REDUCy / APHP241012
- Keywords
- Cyclophosphamide toxicities, Cyclophosphamide dose reduction, Graft-Versus-Host Disease: GVHD, Hematopoietic stem cell transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jun 2026 (estimated)
- Primary completion
- Jun 2030 (estimated)
- Study completion
- Jun 2030 (estimated)
- First posted
- 25 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The randomization will be stratified by age (< 60 years versus ≥ 60 years), disease risk index (low and intermediate versus high and very-high), and antithymocyte globulin use (yes versus no).
| Arm | Type | Receives |
|---|---|---|
| Reduced dose | Experimental | Drug: Cyclophosphamide 35mg/kg/daycyclophosphamide administered at 35mg/kg/day (Adjusted body weight) on days +3 and +4 |
| Standard dose | Active comparator | Drug: Cyclophosphamide 50mg/kg/daycyclophosphamide administered at 50mg/kg/day (Adjusted Body Weight) on days +3 and +4 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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")
Key exclusion criteria (23 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cyclophosphamide 35mg/kg/dayCyclophosphamide 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). | Drug | Reduced dose |
| Cyclophosphamide 50mg/kg/dayCyclophosphamide 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). | Drug | Standard dose |
Primary outcome
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
12 secondary outcomes
Overall survival (OS)
Time frame: From transplantation until death from any cause or up to 24 months, whichever occurs first
Quality of life FACT-BMT
Time frame: At 1, 3, 6, 12, and 24 months after HSCT
Quality of life EQ-5D-5L
Time frame: At 1, 3, 6, 12, and 24 months after HSCT
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
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
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.
Cumulative incidence of relapse
Time frame: From transplantation until the occurrence of relapse or up to 24 months, whichever occurs first
Disease-free survival (DFS)
Time frame: At two years
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
Cost-effectiveness
Time frame: From transplantation until 2 years
Cytokine profiles
Time frame: Inclusion, Day 0, Day 15-35, Day 90, Day 365
Gut microbiota
Time frame: Inclusion, Day 0, Day 15-35, Day 90
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Remy DULERY contact
Mohamad MOHTY, PU-PH principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cyclophosphamide 35mg/kg/day and Cyclophosphamide 50mg/kg/day in people with GVHD - Graft-Versus-Host Disease and HSCT, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohamad MOHTY, PU-PH (00 33 1.49.28.26.20, mohamad.mohty@inserm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026.