Study Testing Two Conditioning Regimen With a Single Prophylaxis of GVHD by Cyclophosphamide and Methotrexate Post-transplant in Patients Eligible for Matched-donor Allograft Transplantation
Randomized Phase 2 Study Testing Two Conditioning Regimen With a Single Prophylaxis of Graft-versus-host Disease by Cyclophosphamide and Methotrexate Post-transplant in Patients Eligible for Matched-donor Allograft Transplantation
Nantes University Hospital
82 participants
Jul 18, 2024
INTERVENTIONAL
Summary
Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-CSH). Recently, in the context of semi-identical (=haploidentical) HLA donors, but also of compatible HLA donors, the use of cyclophosphamide (CY) administered in high doses at early post-transplant (PT) (=PTCY) (Days +3 and +4 or +5) has shown excellent control of acute and chronic GVH, even enabling the discontinuation of other immunosuppressive drugs administered after allo-CSH (ciclosporin, mycophenolate mofetyl (MMF) or Cellcept). This step has already been taken in the context of allo-CSH with myeloablative conditioning (MAC), which is a minoritary conditioning in adults. However, in the context of allo-CSH with reduced-intensity conditioning (RIC), which predominates in adults, this strategy seems insufficient to prevent the risk of GVHD. The idea of reducing the use of immunosuppressants in the context of RIC/HLA-compatible transplants seems, however, still relevant, in order to reduce their adverse effects, improve patients' quality of life and enhance the reconstitution of the post-transplant immune system.
Eligibility
Inclusion Criteria11
- Age: ≥ 18 and ≤ 70 years old
- Patient with hematologic malignancy
- Indication for HSC allograft with attenuated conditioning
- Pluripotent stem cell (PSC) engraftment
- Availability of a 10/10 familial or non-familial HLA compatible donor
- Consent to the protocol
- ECOG <=2
- Woman of childbearing age with negative pregnancy test and on highly effective contraception during treatment and for a period of 12 months after stopping MTX and CY
- Man of childbearing age with highly effective contraception during treatment and for a period of 6 months after stopping MTX and CY and a period of 12 months after stopping MTX and CY if TBF conditioning regimen arm
- Negative Hepatitis B, C, HIV serologies
- Social security affiliation
Exclusion Criteria18
- History of allograft
- Patient eligible for myeloablative conditioning (MAC)
- Bone marrow transplant
- Other progressive cancerous disease, or antecedent of cancer in the last five years, with the exception of a carcinoma of the skin or a carcinoma in situ of the uterine cole treated and in remission.
- Progressive psychiatric condition
- Pregnant or breastfeeding woman,
- Woman or man of childbearing age with lack of effective contraception
- Serious and uncontrolled concomitant infection
- Cardiac: systolic ejection fraction < 50% by transthoracic ultrasound or by isotopic method (isotope gamma angiography), NYHA II, III or IV heart failure, active rhythmic, valvular or ischemic heart disease or anteriority
- Respiratory with EFR: DLCOc <40% of theoretical
- Renal: creatinine clearance < 50 ml/min (assessment with MDRD method)
- Urological: active urinary tract infection, history of acute urothelial toxicity due to cytotoxic chemotherapy or radiotherapy, known obstruction of urinary flow, pre-existing hemorrhagic cystitis
- Hepatic: transaminases greater than 5 times normal or bilirubin greater than 2 times normal
- Person protected by law (major under guardianship, curatorship or legal protection)
- Vaccination against yellow fever in the last year
- Known or suspected hypersensitivity to rabbit proteins as well as to the active substance and excipients of all investigational and ancillary drugs administered during the study,
- Contraindication to any of the investigational or adjuvant drugs administered during the study
- Patient not speaking French
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Interventions
15 mg/m² on Day+1 after graft (=Day0) 10 mg/m² 3 days on Day+4/Day+6/Day+11 after graft (=Day0)
50 mg/kg intravenous 2 days on Day+3/Day+5 after graft (=Day0)
Conditioning regimen: 30 mg/m² Intravenous 5 days from Day-6 to Day-2 (Day-6/Day-5-/Day-4/Day-3/Day-2 before graft (=Day0)
Conditioning regimen: 14.5 mg/kg intravenous 2 days on Day-6/Day-5 before graft (=Day0)
Conditioning regimen: 2.5 mg/kg intravenous on Day-2 before graft (=Day0)
2 grays on Day-1 before graft (=Day0)
High dose of hematopoietic stem cells derived from peripheral blood on transplantation day (=Day0 graft)
Graft nuclear cells CD3+ cells if needed after transplantation
DLI with CD3+ if relapse after transplantation or in prevention of relapse
Conditioning regimen: 30 mg/m² Intravenous 5 days from Day-6 to Day-2 (Day-6/Day-5-/Day-4/Day-3/Day-2 before graft (=Day0)
Conditioning regimen: 5 mg/kg Intravenous at Day-6 before graft (=Day0)
Conditioning regimen: 3.2 mg/kg Intravenous 2 days at Day-2 and Day-1 before graft (=Day0)
Conditioning regimen: 40 mg/m² intravenous 4 days on Day-5/Day-4/Day-3/Day-2 before graft (=Day0)
Locations(3)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06252870