Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2024-519986-23-00 | EU Trial (CTIS) Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Reduced dose | Experimental | cyclophosphamide administered at 35mg/kg/day (Adjusted body weight) on days +3 and +4 |
|
| Standard dose | Active Comparator | cyclophosphamide administered at 50mg/kg/day (Adjusted Body Weight) on days +3 and +4 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival (OS) | Overall survival (OS) at 2 years is defined as survival irrespective of disease status | From transplantation until death from any cause or up to 24 months, whichever occurs first |
| Quality of life FACT-BMT |
Not provided
Inclusion Criteria:
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:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mohamad MOHTY, PU-PH | Contact | 00 33 1.49.28.26.20 | mohamad.mohty@inserm.fr | |
| Remy DULERY | Contact | remy.dulery@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Mohamad MOHTY, PU-PH | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Saint Antoine Hospital - Hematology Department | Paris | 75012 | France |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
Not provided
Not provided
Not provided
Not provided
| 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). |
|
Quality of life compared to baseline using questionnaire: FACT-BMT (Functional Assessment of Cancer Therapy - Bone Marrow Transplant, version 4)
| 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). | 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 | 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 | 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 | 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 | 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 | 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 | 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. | 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 | 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 | Inclusion, Day 0, Day 15-35, Day 90 |
| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
Not provided
Not provided