Graft Versus Host DiseasePhase 2CYRICNCT03263767
Post Transplant Cyclophosphamide (PTCY) as Sole Graft Versus Host Disease (GVHD) Prophylaxis for Matched Allotransplant: CYRIC
A Phase 2 study testing Fludarabine, Clofarabine and Full body irradiation in people with Graft Versus Host Disease, run by Nantes University Hospital at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- Fludarabine, Clofarabine and Full body irradiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteFrance
- Study dates
- 15 Jan 2018to 21 Jun 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- - 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
Show all 25Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study Testing Prophylaxis Feasibility of Graft Versus Host Disease With Only High Dose Cyclophosphamide Post-transplantation for Patients Eligible to a Reduced-intensity Conditioning Regiment Prior to Allogenic Transplantation With a Compatible Familial or Non-familial Donor.
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.
Read the detailed 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.
- Conditions
- Graft Versus Host Disease
- Being tested
- Fludarabine, Clofarabine, Full body irradiation, Cyclophosphamide, stem cell transplantation
- Keywords
- Peripheral haemopoietic stem cell transplant, High dose cyclophosphamide, acute GVHD, allogenic transplantation, RIC (reduced-intensity conditioning)
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
30 mg/m² Intravenous 5 days from Day-6 to Day-2
ClofarabineDrug
30 mg/m² Intravenous 5 days from Day-6 to Day-2
Full body irradiationRadiation
2 grays at Day-1
CyclophosphamideDrug
14 mg/kg intravenous 2 days at Day - 6 and day -5
CyclophosphamideDrug
Also called hight dose
50 mg/kg intravenous 2 days at day +3 and day +4
stem cell transplantationOther
Also called graft
at D0 intraveinous Depending on donor : the stem cells will be extracted from blood (CD34+) or from bone marrow (CD34+ and nuclear cells)
nuclear cellsOther
Also called Donor Lymphocytes Injection (DLI)
CD3+ cells if needed after transplantation
Thymoglobulin Injectable ProductDrug
Also called ATG
At day -2 2.5 mg/kg for patients inclued after 14 dec 2020
| Study group | Role | What they receive |
|---|---|---|
| LYMPHOID HEMOPATHY without ATG | Experimental | patients with lymphoid hemopathy Receives: Drug: Fludarabine; Radiation: Full body irradiation; Drug: Cyclophosphamide; Other: stem cell transplantation; Other: nuclear cells |
| MYELOID HEMOPATHY without ATG | Experimental | patients with myeloid hemopathy Receives: 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 Receives: 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 Receives: Drug: Clofarabine; Radiation: Full body irradiation; Drug: Cyclophosphamide; Other: stem cell transplantation; Other: nuclear cells; Drug: Thymoglobulin Injectable Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of grade 3 and 4 acute GVHD cortico-resistant
acute GVHD will be evaluated from International Mount Sinai criteria
Measured: 100 days after transplantation
Secondary outcomes (19)
Engraftment
number of days in aplasia (neutrophils< 0.5 Giga/L and platelets<20 G/l, number of transfusions (red blood and platelets)
Measured: one year
Engraftment
chimerism
Measured: one year
disease free survival (DFS)
blood and bone marrow analysis
Measured: one year, the last follow-up visit
Overall survival (OS)
clinical follow-up
Measured: one year, the last follow-up visit
graft and relapse free survival
time between Day O and relapse
Measured: one year
chronic GVHD
chronic GVHD will be assessed with NCI criteria for evaluation of chronic GVHD
Measured: one year
non relapse mortality (NRM)
number of death unrelated to relapse or disease progression
Measured: last follow-up visit
Chimerism
proportion of full and mixed donor chimerism
Measured: 1, 2, 3, 6 and 12 months after transplantation
Immune reconstitution
lymphocytes, monocytes, T4, T8, Natural Killer (NK), B cells rates
Measured: 3, 6 and 12 months after transplantation
Identification of ghost factors associated with GVHD
Statistical Models to Identify Subjects with Ghost Prognosis Factors Nguyen JM. 2015
Measured: one year
Adverse events of grade 3 and 4 after transplantation
time of occurring and frequency of grade 3 and grade 4 adverse events (CTCAE criteria)
Measured: one year
Infections frequency
time of occurring and frequency of viral (CytoMegalo Virus, Epstein Barr virus , BKV, adenovirus), bacterial, parasite and yeast infections, evaluated by Polymerase Chain Reaction (PCR), blood and urines cultures, biopsy if applicable
Measured: one year
compare OS between patients with ATG and patients without ATG
OS
Measured: one year, last follow-up visit
compare grade 2-4 and 3-4 acute GVHD between patients with ATG and patients without ATG
acute GVHD will be evaluated from International Mount Sinai criteria
Measured: one year
compare chronic GVHD between patients with ATG and patients without ATG
chronic GVHD will be assessed with NCI criteria for evaluation of chronic GVHD
Measured: one year
compare DFS between patients with ATG and patients without ATG
DFS
Measured: one year, last follow-up visit
compare Relapse between patients with ATG and patients without ATG
Relapse
Measured: one year, last follow-up visit
compare NRM between patients with ATG and patients without ATG
NRM
Measured: one year, last follow-up visit
compare Infections frequency between patients with ATG and patients without ATG
time of occurring and frequency of viral (CytoMegalo Virus, Epstein Barr virus , BKV, adenovirus), bacterial, parasite and yeast infections, evaluated by Polymerase Chain Reaction (PCR), blood and urines cultures, biopsy if applicable
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2017
- Study start15 Jan 2018
- Primary completion21 Oct 2021
- Study completion21 Jun 2022
Why it stopped: Security criteria (MTD)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03263767
- Sponsor's protocol ID
- RC16_0435
- Acronym
- CYRIC
- Status last verified
- Jul 2022
- First submitted
- 21 Aug 2017
- Last updated
- 15 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study Testing Prophylaxis Feasibility of Graft Versus Host Disease With Only High Dose Cyclophosphamide Post-transplantation for Patients Eligible to a Reduced-intensity Conditioning Regiment Prior to Allogenic Transplantation With a Compatible Familial or Non-familial Donor.
- ClinicalTrials.gov ID
- NCT03263767
- Acronym / sponsor ID
- CYRIC / RC16_0435
- Conditions
- Graft Versus Host Disease
- Keywords
- Peripheral haemopoietic stem cell transplant, High dose cyclophosphamide, acute GVHD, allogenic transplantation, RIC (reduced-intensity conditioning)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Security criteria (MTD)
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- 15 Jan 2018 (actual)
- Primary completion
- 21 Oct 2021 (actual)
- Study completion
- 21 Jun 2022 (actual)
- First posted
- 28 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| LYMPHOID HEMOPATHY without ATG | Experimental | Drug: Fludarabine, Radiation: Full body irradiation, Drug: Cyclophosphamide, Other: stem cell transplantation, Other: nuclear cellspatients with lymphoid hemopathy |
| MYELOID HEMOPATHY without ATG | Experimental | Drug: Clofarabine, Radiation: Full body irradiation, Drug: Cyclophosphamide, Other: stem cell transplantation, Other: nuclear cellspatients with myeloid hemopathy |
| LYMPHOID HEMOPATHY witH ATG | Experimental | Drug: Fludarabine, Radiation: Full body irradiation, Drug: Cyclophosphamide, Other: stem cell transplantation, Other: nuclear cells, Drug: Thymoglobulin Injectable Productpatients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence |
| MYELOID HEMOPATHY with ATG | Experimental | Drug: Clofarabine, Radiation: Full body irradiation, Drug: Cyclophosphamide, Other: stem cell transplantation, Other: nuclear cells, Drug: Thymoglobulin Injectable Productpatients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (25 listed)
- - 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fludarabine30 mg/m² Intravenous 5 days from Day-6 to Day-2 | Drug | LYMPHOID HEMOPATHY witH ATG, LYMPHOID HEMOPATHY without ATG |
| Clofarabine30 mg/m² Intravenous 5 days from Day-6 to Day-2 | Drug | MYELOID HEMOPATHY with ATG, MYELOID HEMOPATHY without ATG |
| Full body irradiation2 grays at Day-1 | Radiation | LYMPHOID HEMOPATHY witH ATG, LYMPHOID HEMOPATHY without ATG, MYELOID HEMOPATHY with ATG, MYELOID HEMOPATHY without ATG |
| Cyclophosphamide14 mg/kg intravenous 2 days at Day - 6 and day -5 | Drug | LYMPHOID HEMOPATHY witH ATG, LYMPHOID HEMOPATHY without ATG, MYELOID HEMOPATHY with ATG, MYELOID HEMOPATHY without ATG |
| CyclophosphamideAlso: hight dose50 mg/kg intravenous 2 days at day +3 and day +4 | Drug | LYMPHOID HEMOPATHY witH ATG, LYMPHOID HEMOPATHY without ATG, MYELOID HEMOPATHY with ATG, MYELOID HEMOPATHY without ATG |
| stem cell transplantationAlso: graftat D0 intraveinous Depending on donor : the stem cells will be extracted from blood (CD34+) or from bone marrow (CD34+ and nuclear cells) | Other | LYMPHOID HEMOPATHY witH ATG, LYMPHOID HEMOPATHY without ATG, MYELOID HEMOPATHY with ATG, MYELOID HEMOPATHY without ATG |
| nuclear cellsAlso: Donor Lymphocytes Injection (DLI)CD3+ cells if needed after transplantation | Other | LYMPHOID HEMOPATHY witH ATG, LYMPHOID HEMOPATHY without ATG, MYELOID HEMOPATHY with ATG, MYELOID HEMOPATHY without ATG |
| Thymoglobulin Injectable ProductAlso: ATGAt day -2 2.5 mg/kg for patients inclued after 14 dec 2020 | Drug | LYMPHOID HEMOPATHY witH ATG, MYELOID HEMOPATHY with ATG |
Primary outcome
Incidence of grade 3 and 4 acute GVHD cortico-resistant
Time frame: 100 days after transplantation
acute GVHD will be evaluated from International Mount Sinai criteria
19 secondary outcomes
Engraftment
Time frame: one year
Engraftment
Time frame: one year
disease free survival (DFS)
Time frame: one year, the last follow-up visit
Overall survival (OS)
Time frame: one year, the last follow-up visit
graft and relapse free survival
Time frame: one year
chronic GVHD
Time frame: one year
non relapse mortality (NRM)
Time frame: last follow-up visit
Chimerism
Time frame: 1, 2, 3, 6 and 12 months after transplantation
Immune reconstitution
Time frame: 3, 6 and 12 months after transplantation
Identification of ghost factors associated with GVHD
Time frame: one year
Adverse events of grade 3 and 4 after transplantation
Time frame: one year
Infections frequency
Time frame: one year
compare OS between patients with ATG and patients without ATG
Time frame: one year, last follow-up visit
compare grade 2-4 and 3-4 acute GVHD between patients with ATG and patients without ATG
Time frame: one year
compare chronic GVHD between patients with ATG and patients without ATG
Time frame: one year
compare DFS between patients with ATG and patients without ATG
Time frame: one year, last follow-up visit
compare Relapse between patients with ATG and patients without ATG
Time frame: one year, last follow-up visit
compare NRM between patients with ATG and patients without ATG
Time frame: one year, last follow-up visit
compare Infections frequency between patients with ATG and patients without ATG
Time frame: one year
Results and safety
The study was stopped early (reason given: Security criteria (MTD)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fludarabine, Clofarabine and Full body irradiation in people with Graft Versus Host Disease, run by Nantes University Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Security criteria (MTD)). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of grade 3 and 4 acute GVHD cortico-resistant (time frame: 100 days after transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2022.