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

NCT ID: NCT03263767

Last Updated: 2022-07-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-15

Study Completion Date

2022-06-21

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Graft Versus Host Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LYMPHOID HEMOPATHY without ATG

patients with lymphoid hemopathy

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

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

Full body irradiation

Intervention Type RADIATION

2 grays at Day-1

Cyclophosphamide

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

50 mg/kg intravenous 2 days at day +3 and day +4

stem cell transplantation

Intervention Type OTHER

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

nuclear cells

Intervention Type OTHER

CD3+ cells if needed after transplantation

MYELOID HEMOPATHY without ATG

patients with myeloid hemopathy

Group Type EXPERIMENTAL

Clofarabine

Intervention Type DRUG

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

Full body irradiation

Intervention Type RADIATION

2 grays at Day-1

Cyclophosphamide

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

50 mg/kg intravenous 2 days at day +3 and day +4

stem cell transplantation

Intervention Type OTHER

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

nuclear cells

Intervention Type OTHER

CD3+ cells if needed after transplantation

LYMPHOID HEMOPATHY witH ATG

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

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

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

Full body irradiation

Intervention Type RADIATION

2 grays at Day-1

Cyclophosphamide

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

50 mg/kg intravenous 2 days at day +3 and day +4

stem cell transplantation

Intervention Type OTHER

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

nuclear cells

Intervention Type OTHER

CD3+ cells if needed after transplantation

Thymoglobulin Injectable Product

Intervention Type DRUG

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

MYELOID HEMOPATHY with ATG

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

Group Type EXPERIMENTAL

Clofarabine

Intervention Type DRUG

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

Full body irradiation

Intervention Type RADIATION

2 grays at Day-1

Cyclophosphamide

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

50 mg/kg intravenous 2 days at day +3 and day +4

stem cell transplantation

Intervention Type OTHER

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

nuclear cells

Intervention Type OTHER

CD3+ cells if needed after transplantation

Thymoglobulin Injectable Product

Intervention Type DRUG

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

Interventions

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Fludarabine

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

Intervention Type DRUG

Clofarabine

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

Intervention Type DRUG

Full body irradiation

2 grays at Day-1

Intervention Type RADIATION

Cyclophosphamide

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

Intervention Type DRUG

Cyclophosphamide

50 mg/kg intravenous 2 days at day +3 and day +4

Intervention Type DRUG

stem cell transplantation

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

Intervention Type OTHER

nuclear cells

CD3+ cells if needed after transplantation

Intervention Type OTHER

Thymoglobulin Injectable Product

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

Intervention Type DRUG

Other Intervention Names

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hight dose graft Donor Lymphocytes Injection (DLI) ATG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nantes University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Nantes Uh

Nantes, , France

Site Status

Countries

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France

Other Identifiers

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RC16_0435

Identifier Type: -

Identifier Source: org_study_id

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