NCT02876679

Brief Summary

The study is designed as a two arm randomized Phase II, multicenter trial comparing cyclophosphamide to anti-thymocyte globulin for Graft-versus-Host Disease (GVHD) prophylaxis in patients with hematologic malignancies undergoing reduced intensity conditioning hematopoietic stem cell transplantation.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
94

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Apr 2017

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 12, 2016

Completed
12 days until next milestone

First Posted

Study publicly available on registry

August 24, 2016

Completed
8 months until next milestone

Study Start

First participant enrolled

April 6, 2017

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 12, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 12, 2020

Completed
Last Updated

November 20, 2020

Status Verified

November 1, 2020

Enrollment Period

3.5 years

First QC Date

August 12, 2016

Last Update Submit

November 19, 2020

Conditions

Keywords

Hematopoietic Stem CellTransplantationGraft vs Host DiseaseCyclophosphamideAnti-Thymocyte GlobulinGVHD prophylaxis

Outcome Measures

Primary Outcomes (1)

  • Composite endpoint of GVHD-free, relapse-free survival (GRFS)

    Absence of grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death

    12 Months

Secondary Outcomes (7)

  • Cumulative incidence of grade 2-4 and grade 3-4 severe acute GVHD

    6 Months

  • Cumulative incidence of non-relapse mortality within the first 12 months after transplantation.

    12 Months

  • Disease-free survival

    12 months

  • Overall survival.

    12 months

  • Quality of Life (QoL) with EORTC QLQ-C30

    12 Months

  • +2 more secondary outcomes

Study Arms (2)

Cyclophosphamide

EXPERIMENTAL

50mg/Kg/day cyclophosphamide (day +3 and +4)

Drug: CyclophosphamideDrug: Conditioning regimen

Anti-Thymocyte Globulin

ACTIVE COMPARATOR

2.5 mg/Kg/day ATG (Thymoglobuline®) for 2 consecutive days (day -2 and -1)

Drug: Anti-Thymocyte GlobulinDrug: Conditioning regimen

Interventions

GVHD prophylaxis: All patients will receive post-transplant 50mg/Kg/day cyclophosphamide (day +3 and +4) AND cyclosporine-A alone in case of an HLA-sibling donor, or cyclosporine-A and mycophenolate-mofetil in case of an HLA-matched unrelated donor

Also known as: Cyclophosphamide + cyclosporine-A +/-mycophenolate-mofetil
Cyclophosphamide

GVHD prophylaxis: 2.5 mg/Kg/day ATG (Thymoglobuline®) for 2 consecutive days (day -2 and -1) All patients will receive cyclosporine-A alone in case of an HLA-sibling donor, or cyclosporine-A and mycophenolate-mofetil (MMF) in case of an HLA-matched unrelated donor.

Also known as: Anti-Thymocyte Globulin + cyclosporine-A +/-mycophenolate-mofetil
Anti-Thymocyte Globulin

30 mg/m2/day fludarabine for 5 days (day-6 to day-2) 130 mg/m2/day IV busulfan once daily for 2 days (day -4 and -3)

Anti-Thymocyte GlobulinCyclophosphamide

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients aged between 18 and 65 years
  • Presence of a hematologic malignancy for which a reduced-intensity conditioning allo-SCT is indicated (eligibility criteria for RIC allo-SCT include at least one of the following parameters: (i) patient age older than 50 years; (ii) heavily pre-treated patients who received an autologous hematopoietic SCT (auto-SCT) or with more than 2 lines of chemotherapy before allo-SCT; and (iii) patients with poor performance status because of significant medical comorbidities as described by Sorror et al.
  • Karnofsky index ≥ 70%
  • Availability of a sibling or unrelated stem-cell donor (10/10-HLA matched unrelated donor)
  • Efficient contraceptive method within 1 month for women and 3 months for men after the last dose of treatment
  • Written informed consent.

You may not qualify if:

  • Creatinine clearance less than 30 mL/min
  • Bilirubin or amino-transferases above 3X upper normal limit
  • Cardiac ejection fraction less than 40%
  • Pulmonary impairment with \<50% lung carbon monoxide diffusing capacity (DLCO)
  • Known hypersensitivity or contraindication to the use of post-transplant Cy and ATG
  • Any circumstance that precludes the use of the drugs involved in the protocol
  • Pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Saint Antoine Hospital - Hematology Department

Paris, 75012, France

Location

Related Publications (2)

  • Brissot E, Labopin M, Labussiere H, Fossard G, Chevallier P, Guillaume T, Yakoub-Agha I, Srour M, Bulabois CE, Huynh A, Chantepie S, Menard AL, Rubio MT, Ceballos P, Dulery R, Furst S, Malard F, Blaise D, Mohty M. Post-transplant cyclophosphamide versus anti-thymocyte globulin after reduced intensity peripheral blood allogeneic cell transplantation in recipients of matched sibling or 10/10 HLA matched unrelated donors: final analysis of a randomized, open-label, multicenter, phase 2 trial. Blood Cancer J. 2024 Feb 19;14(1):31. doi: 10.1038/s41408-024-00990-3.

  • Del Pozo Martin Y. 47th Annual Meeting of the EBMT. Lancet Haematol. 2021 May;8(5):e317-e318. doi: 10.1016/S2352-3026(21)00104-6. Epub 2021 Mar 31. No abstract available.

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

CyclophosphamideAntilymphocyte SerumTransplantation Conditioning

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsImmune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex MixturesImmunosuppression TherapyImmunotherapyImmunomodulationBiological TherapyTherapeuticsImmunologic TechniquesInvestigative Techniques

Study Officials

  • Mohamad MOHTY, PU-PH

    Assistance Publique - Hôpitaux de Paris

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 12, 2016

First Posted

August 24, 2016

Study Start

April 6, 2017

Primary Completion

October 12, 2020

Study Completion

October 12, 2020

Last Updated

November 20, 2020

Record last verified: 2020-11

Data Sharing

IPD Sharing
Will not share

Locations