Trial Title:
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
NCT ID:
NCT06252870
Condition:
Graft Versus Host Disease
Hematologic Malignancy
Conditions: Official terms:
Hematologic Neoplasms
Graft vs Host Disease
Vidarabine
Cyclophosphamide
Busulfan
Thiotepa
Methotrexate
Fludarabine
Fludarabine phosphate
Clofarabine
Thymoglobulin
Antilymphocyte Serum
Conditions: Keywords:
Hematopoietic stem cell allograft (Allo-CSH)
Methotrexate (MTX)
Post-transplant cyclophosphamide (PTCY)
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Multicenter, phase 2, non-comparative, randomized, open-label, prospective drug trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Methotrexate
Description:
15 mg/m² on Day+1 after graft (=Day0) 10 mg/m² 3 days on Day+4/Day+6/Day+11 after graft
(=Day0)
Arm group label:
(CLO)-BALTIMORE
Arm group label:
TBF
Other name:
MTX
Intervention type:
Drug
Intervention name:
Post-Transplant Cyclophosphamide
Description:
50 mg/kg intravenous 2 days on Day+3/Day+5 after graft (=Day0)
Arm group label:
(CLO)-BALTIMORE
Arm group label:
TBF
Other name:
CY
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
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)
Arm group label:
(CLO)-BALTIMORE
Other name:
Fludarabine Baltimore
Intervention type:
Drug
Intervention name:
Cycophosphamide
Description:
Conditioning regimen: 14.5 mg/kg intravenous 2 days on Day-6/Day-5 before graft (=Day0)
Arm group label:
(CLO)-BALTIMORE
Intervention type:
Drug
Intervention name:
Anti-Thymoglobulin
Description:
Conditioning regimen: 2.5 mg/kg intravenous on Day-2 before graft (=Day0)
Arm group label:
(CLO)-BALTIMORE
Arm group label:
TBF
Other name:
ATG
Intervention type:
Radiation
Intervention name:
total body irradiation
Description:
2 grays on Day-1 before graft (=Day0)
Arm group label:
(CLO)-BALTIMORE
Other name:
TBI
Intervention type:
Other
Intervention name:
hematopoietic stem cells
Description:
High dose of hematopoietic stem cells derived from peripheral blood on transplantation
day (=Day0 graft)
Arm group label:
(CLO)-BALTIMORE
Arm group label:
TBF
Other name:
HSC
Intervention type:
Other
Intervention name:
Graft nuclear cells
Description:
Graft nuclear cells CD3+ cells if needed after transplantation
Arm group label:
(CLO)-BALTIMORE
Arm group label:
TBF
Intervention type:
Other
Intervention name:
Donor Lymphocytes Injection
Description:
DLI with CD3+ if relapse after transplantation or in prevention of relapse
Arm group label:
(CLO)-BALTIMORE
Arm group label:
TBF
Other name:
DLI
Intervention type:
Drug
Intervention name:
Clofarabine
Description:
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)
Arm group label:
(CLO)-BALTIMORE
Intervention type:
Drug
Intervention name:
Thiotepa
Description:
Conditioning regimen: 5 mg/kg Intravenous at Day-6 before graft (=Day0)
Arm group label:
TBF
Intervention type:
Drug
Intervention name:
Busulfan
Description:
Conditioning regimen: 3.2 mg/kg Intravenous 2 days at Day-2 and Day-1 before graft
(=Day0)
Arm group label:
TBF
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Conditioning regimen: 40 mg/m² intravenous 4 days on Day-5/Day-4/Day-3/Day-2 before graft
(=Day0)
Arm group label:
TBF
Other name:
Fludarabine TBF
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.
Detailed description:
For this reason, the investigators now wish to test the administration of a combination
of a high dose of early post-transplant CY (PTCY) and methotrexate (MTX) on days (D) D+1,
D+4, D+6, D+11 (doses already performed in MAC transplant prophylaxis), with
anti-lymphocyte serum (ALS) with RIC conditioning, without ciclosporin or MMF.
The investigators hypothesize that administration of this PTCY+MTX combination will
enable immunosuppressive drugs to be discontinued as early as D+11 post-transplant,
compared with the usual average of 3 to 4 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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 Criteria:
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
CHU Angers
Address:
City:
Angers
Country:
France
Status:
Recruiting
Contact:
Last name:
Sylvain THEPOT, MD
Phone:
0241354482
Phone ext:
+33
Email:
sylvain.thepot@chu-angers.fr
Facility:
Name:
CHU Brest
Address:
City:
Brest
Country:
France
Status:
Recruiting
Contact:
Last name:
Marie-Anne COUTURIER, MD
Phone:
0298223765
Phone ext:
+33
Email:
marie-anne.couturier@chu-brest.fr
Facility:
Name:
CHU Nantes
Address:
City:
Nantes
Country:
France
Status:
Recruiting
Contact:
Last name:
Amandine LE BOURGEOIS, MD
Phone:
0240083271
Phone ext:
+33
Email:
amandine.lebourgeois@chu-nantes.fr
Start date:
July 18, 2024
Completion date:
July 18, 2028
Lead sponsor:
Agency:
Nantes University Hospital
Agency class:
Other
Source:
Nantes University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06252870
