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

NCT03263767 | Terminated Phase 2

• 1 other identifier: RC16_0435
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Graft Versus Host Disease

Keywords

Peripheral haemopoietic stem cell transplant; High dose cyclophosphamide; acute GVHD; allogenic transplantation; RIC (reduced-intensity conditioning)

Outcome Measures

Primary Outcomes (1)

• Incidence of grade 3 and 4 acute GVHD cortico-resistant

  acute GVHD will be evaluated from International Mount Sinai criteria

  100 days after transplantation

Secondary Outcomes (19)

• Engraftment

  one year

• Engraftment

  one year

• disease free survival (DFS)

  one year, the last follow-up visit

• Overall survival (OS)

  one year, the last follow-up visit

• graft and relapse free survival

  one year

Study Arms (4)

LYMPHOID HEMOPATHY without ATG

EXPERIMENTAL

patients with lymphoid hemopathy

Drug: Fludarabine; Radiation: Full body irradiation; Drug: Cyclophosphamide; Other: stem cell transplantation; Other: nuclear cells

MYELOID HEMOPATHY without ATG

EXPERIMENTAL

patients with myeloid hemopathy

Drug: Clofarabine; Radiation: Full body irradiation; Drug: Cyclophosphamide; Other: stem cell transplantation; Other: nuclear cells

LYMPHOID HEMOPATHY witH ATG

EXPERIMENTAL

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

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

MYELOID HEMOPATHY with ATG

EXPERIMENTAL

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

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

Interventions

Fludarabine DRUG

30 mg/m² Intravenous 5 days from Day-6 to Day-2

LYMPHOID HEMOPATHY witH ATG; LYMPHOID HEMOPATHY without ATG

Clofarabine DRUG

30 mg/m² Intravenous 5 days from Day-6 to Day-2

MYELOID HEMOPATHY with ATG; MYELOID HEMOPATHY without ATG

Full body irradiation RADIATION

2 grays at Day-1

LYMPHOID HEMOPATHY witH ATG; LYMPHOID HEMOPATHY without ATG; MYELOID HEMOPATHY with ATG; MYELOID HEMOPATHY without ATG

Cyclophosphamide DRUG

14 mg/kg intravenous 2 days at Day - 6 and day -5

LYMPHOID HEMOPATHY witH ATG; LYMPHOID HEMOPATHY without ATG; MYELOID HEMOPATHY with ATG; MYELOID HEMOPATHY without ATG

stem cell transplantation OTHER

at D0 intraveinous Depending on donor : the stem cells will be extracted from blood (CD34+) or from bone marrow (CD34+ and nuclear cells)

Also known as: graft

LYMPHOID HEMOPATHY witH ATG; LYMPHOID HEMOPATHY without ATG; MYELOID HEMOPATHY with ATG; MYELOID HEMOPATHY without ATG

nuclear cells OTHER

CD3+ cells if needed after transplantation

Also known as: Donor Lymphocytes Injection (DLI)

LYMPHOID HEMOPATHY witH ATG; LYMPHOID HEMOPATHY without ATG; MYELOID HEMOPATHY with ATG; MYELOID HEMOPATHY without ATG

Thymoglobulin Injectable Product DRUG

At day -2 2.5 mg/kg for patients inclued after 14 dec 2020

Also known as: ATG

LYMPHOID HEMOPATHY witH ATG; MYELOID HEMOPATHY with ATG

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \- 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

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

Nantes Uh

Nantes, France

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

fludarabine; Clofarabine; Cyclophosphamide; Stem Cell Transplantation; Transplantation

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: August 28, 2017
• Study Start: January 15, 2018
• Primary Completion: October 21, 2021
• Study Completion: June 21, 2022
• Last Updated: July 15, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)