Post Transplant Cyclophosphamide (PTCY) as Sole Graft Versus Host Disease (GVHD) Prophylaxis for Matched Allotransplant: CYRIC

Nantes University Hospital (NUH)

Status and phase: Terminated; Phase 2

Conditions: Graft Versus Host Disease

Treatments: Drug: Thymoglobulin Injectable Product; Drug: Clofarabine; Radiation: Full body irradiation; Other: stem cell transplantation; Drug: Fludarabine; Drug: Cyclophosphamide; Other: nuclear cells

Study type: Interventional

Funder types: Other

Identifiers

NCT03263767

RC16_0435

Details and patient eligibility

About

Acute or chronic graft versus host disease is still the major complication of stem cells transplantation regarding morbidity and mortality.

Recently, high dose cyclophosphamide utilization early after post-transplantation (day+ 3 and +4) not only for patients with HLA- haploidentical donor but also for patients with Human Leukocyte Antigen (HLA)-compatible donor, showed a great control of graft versus host disease after transplantation, allowing to consider stopping immunosuppressive treatment after the transplantation (Neoral=cyclosporine, cell-cept=mycophenolate mofetil). Indeed, this step has already been completed in myeloablative transplantation in adult patients.

This approach could enable to avoid in the end several complications related to long term immunosuppressive drugs administration, while promoting quicker immunity recovery.

Full description

The BALTIMORE conditioning regiment will be used in this study with peripheral stem cell transplantation and fludarabine will be replaced by clofarabine for myeloid diseases (Acute Myeloide Leukemia, Myelodysplasia , myelofibrosis, Chronic Myeoloid Leukemia..) because of better antitumoral activity in this setting.

Enrollment: 47 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• adults ≤ 70 years old
• indication to stem cells transplantation with reduced-intensity conditioning regimen
• with a HLA-compatible familial 10/10 or non-familial donor
• Written signed informed consent form
• woman with childbearing potential under efficient control birth method during the trial and up to 12 months after cyclophosphamide stop
• men under efficient control birth method during the trial and up to 6 months after cyclophosphamide stop
• Negative serology to B and C hepatitis and to HIV
• Affiliated to social security

Exclusion criteria

• • Eligible to myeloablative contioning regimen

• Other progressive malignancy disease or history of prior other malignancy in the last two years, with the exception of: curatively treated basal cell carcinoma or carcinoma in situ of the cervix

• Progressive mental illness disease

• Pregnant or Breastfeeding woman

• woman with childbearing potential without any efficient control birth

• Serious concomitant infection and not controlled

• Contra-indications to allogenic transplantation, especially:

  • Cardiac: left ventricular ejection fraction <45% assessed by transthoracic echography or isotopic method (isotopic gamma-angiography)
  • Respiratory: DLCO limiting fludarabine and busulfan use (DLCO< 40% of theorical value)
  • Renal: creatinine clearance < 60ml/min (MDRD method)
  • Hepatic: transaminases >5 Uper Per Normal (UPN) or bilirubin> 2 UPN

• Contra-indications to cyclophosphamide:

  • Urinary tract infections
  • Acute urothelial toxicity due to cytotoxic chemotherapy or to radiotherapy
  • Obstruction of urines flow
  • Pre-existing hemorrhagic cystitis
  • Yellow fever vaccination

• Cardiac condition preventing high dose cyclophosphamide utilization :

  • New York Heart Association (NYHA) functional class II, III or IV
  • Rhythmic, valvular or ischemic cardiomyopathy

• Minor

• Patient under guardianship or curatorship

• Patient under judicial protection

• Known or suspected hypersensitivity to cyclophosphamide

• Known or suspected hypersensitivity to rabbit proteins

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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47 participants in 4 patient groups

LYMPHOID HEMOPATHY without ATG

Experimental group

Description:

patients with lymphoid hemopathy

Treatment:

Other: nuclear cells

Drug: Fludarabine

Drug: Cyclophosphamide

Radiation: Full body irradiation

Other: stem cell transplantation

Drug: Cyclophosphamide

MYELOID HEMOPATHY without ATG

Experimental group

Description:

patients with myeloid hemopathy

Treatment:

Other: nuclear cells

Drug: Clofarabine

Drug: Cyclophosphamide

Radiation: Full body irradiation

Other: stem cell transplantation

Drug: Cyclophosphamide

LYMPHOID HEMOPATHY witH ATG

Experimental group

Description:

patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence

Treatment:

Other: nuclear cells

Drug: Fludarabine

Drug: Cyclophosphamide

Radiation: Full body irradiation

Other: stem cell transplantation

Drug: Thymoglobulin Injectable Product

Drug: Cyclophosphamide

MYELOID HEMOPATHY with ATG

Experimental group

Description:

patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence

Treatment:

Other: nuclear cells

Drug: Clofarabine

Drug: Cyclophosphamide

Radiation: Full body irradiation

Other: stem cell transplantation

Drug: Thymoglobulin Injectable Product

Drug: Cyclophosphamide