Reduced post-transplant cyclophosphamide dose in patients undergoing haploidentical hematopoietic stem cell transplantation for hematological malignancies: a phase III randomized study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2025-07-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective is 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.

Secondary objectives 9

1. Efficacy in terms of overall survival (OS) at 2 years.
2. Efficacy and safety in terms of quality of life, assessed by FACT-BMT (Functional Assessment of Cancer Therapy - Bone Marrow Transplant) and EQ-5D-5L (EuroQol group) questionnaires at 1, 3, 6, 12 and 24 months
3. Safety in terms of hematological recovery, organ-specific toxicities, and infections from HSCT to 2 years, assessed by cumulative incidences and grade.
4. Safety in terms of acute GVHD at 180 days and chronic GVHD at 2 years, assessed by cumulative incidence and grade
5. Safety in terms of transplant-related mortality, assessed by non-relapse mortality (NRM) at 2 years
6. Efficacy and safety in terms of the disease-free survival (DFS) at 2 years.
7. Efficacy and safety in terms of the disease-free survival (DFS) at 2 years
8. Efficacy and safety in terms of the GVHD-free, relapse-free survival (GRFS) at 2 years
9. Cost-effectiveness, assessed by incremental cost-effectiveness (cost per life year) and cost-utility (cost per quality-adjusted life-year, QALY) ratios at 2 years.

Conditions and MedDRA coding

The study will involve adult women and men from 16 French centers who have hematological malignancies and are candidates for haploidentical HSCT

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 18 years
2. Confirmed hematological malignancy with an indication for allogeneic HSCT
3. Presence of a haploidentical donor willing to donate PBSC
4. Patient planned to receive a thiotepa-based conditioning regimen
5. Provision of written informed consent
6. Affiliation to a social security system (excluding “Aide Médicale d’État”)

Exclusion criteria 11

1. Karnofsky performance status < 70%
2. Life expectancy < 1 month, as determined by the attending physician
3. Acute or chronic heart failure, defined as left ventricular ejection fraction < 40%
4. Pulmonary dysfunction with diffusion capacity < 50% of predicted values
5. Renal impairment with estimated glomerular filtration rate (eGFR) < 45 mL/min (calculated using the CKD-EPI formula)
6. Positive HIV status
7. Pregnancy, breast-feeding, or refusal to use effective contraception
8. 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)
9. Hypersensitivity to the active substance or any of the excipients
10. Concurrent participation in another investigational therapeutic study
11. Inability to comply with study procedures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 9

1. Overall survival (OS) at 2 years: From transplantation until death from any cause or up to 24 months, whichever occurs first
2. Quality of life at 1, 3, 6, 12, and 24 months after HSCT compared to baseline using two questionnaires: FACT-BMT (Functional Assessment of Cancer Therapy - Bone Marrow Transplant, version 4) and EQ-5D-5L (EuroQol 5-Dimension, 5-Level questionnaire).
3. 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 109/L) or platelet recovery (platelet count > 50 x 109/L) after HSCT 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
4. Cumulative incidence and severity of acute and chronic GVHD: 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
5. Non-relapse mortality (NRM) at 2 years: From transplantation until death without evidence of relapse or up to 24 months, whichever occurs first
6. Cumulative incidence of relapse at 2 years: From transplantation until the occurrence of relapse or up to 24 months, whichever occurs first
7. Disease-free survival (DFS) at 2 years: From transplantation until relapse or progression of the hematological disease, death, or up to 24 months, whichever occurs first
8. GVHD-free, relapse-free survival (GRFS) at 2 years: From transplantation until the occurrence of acute grade III-IV GVHD, severe chronic GVHD, relapse, death, or up to 24 months, whichever occurs first
9. Incremental cost-effectiveness (cost/life year) and cost-utility (cost/quality-adjusted life-year, QALY) ratios at 2 years.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Scientific Director

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Scientific Director

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications