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

NCT07193420 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: APHP2410122024-519986-23-00
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

GVHD - Graft-Versus-Host Disease; HSCT; Haploidentical Stem Cell Transplantation

Keywords

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

Outcome Measures

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

  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)

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

• Quality of life FACT-BMT

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

• Quality of life EQ-5D-5L

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

• Toxicities, infection and hematogical recovery

  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

  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

Study Arms (2)

Reduced dose

EXPERIMENTAL

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

Drug: Cyclophosphamide 35mg/kg/day

Standard dose

ACTIVE COMPARATOR

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

Drug: Cyclophosphamide 50mg/kg/day

Interventions

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).

Reduced dose

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).

Standard dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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")

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Saint Antoine Hospital - Hematology Department

Paris, 75012, France

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Mohamad MOHTY, PU-PH

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohamad MOHTY, PU-PH

CONTACT

00 33 1.49.28.26.20; mohamad.mohty@inserm.fr

Remy DULERY

CONTACT

remy.dulery@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: July 11, 2025
• First Posted: September 25, 2025
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: May 12, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)