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Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide for Rescuing Patients With Graft Failure

NCT05126186 · Status: NOT_YET_RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 35

Last updated 2021-11-18

No results posted yet for this study

Summary

Prognosis of patients with graft failure is dismal, and re-transplantation is the sole option for long-term survival. Currently, there is no consensus concerning therapeutic options in patients with primary or secondary (within the 60 days post-transplantation) graft failure and finding a new donor within an acceptable delay is challenging. Literature is poor on the subject while the overall survival of such patients is about 30% at 1 year. This situation thus represents today a very challenging unmet medical need.

Recently, haploidentical (haplo) related donor Stem Cell Transplantation (haplo-SCT) have improved dramatically outcomes using T-cell replete grafts with administration of post-transplantation cyclophosphamide (PTCy, which targets alloreactive T cells generated early after an HLA-mismatched transplant, sparing regulatory T cells and leaving unaffected the non-dividing hematopoietic stem cells) and standard post-transplant immune suppression with a calcineurin inhibitor (CNI) and mycophenolate mofetil. Our group re-transplanted a patient who experienced two consecutive graft failures and was successfully managed through a third haplo-SCT from her son using PTCy. We then retrospectively collected and analyzed data from 26 primary graft failure patients transplanted between 2011 and 2017 in 15 centers on behalf of French Society for Stem Cell Transplantation and Cell Therapy (SFGM-TC). The study population consisted mainly of patients with primary or secondary (within the 60 days post-transplantation) graft failure who underwent haplo-SCT and received PTCy as graft-versus-host-disease prophylaxis. The 1-year overall survival was about 60% suggesting that this approach might be a valid option in this particular poor clinical situation but now need validation through a phase II multicenter, national, prospective cohort study.

Conditions

Interventions

OTHER

haplo-SCT with PTCy

Conditioning regimen Fludarabine (30mg/m2/day from day -6 to day -4), Cyclophosphamide (14.5 mg/kg/day at day -6 and day -5) except for patients who received a total dose of Cyclophosphamide \>100mg/Kg during the first Bone Marrow Transplantation Total Body Irradiation (2 Gray on day -1). Source of stem cell source Peripheral blood stem cell Minimal target dose of 4.106 CD34+ cells/kg of recipient GvHD prophylaxis Cyclophosphamide 50 mg/Kg/day at D+3 and D+4 Ciclosporine from day+5 (residual 200 à 300ng/l) Mycophenolate mofetyl at 15mg/Kg x2/day from day+5 Prevention of EBV reactivation Rituximab : 150mg/m2 intravenously at Day+5 post Haplo-SCT Each infusion of Rituximab will be preceded by administration of anti-pyretic and an antihistaminic.

Sponsors & Collaborators

  • Assistance Publique - Hôpitaux de Paris

    lead OTHER

Study Design

Allocation
NA
Purpose
OTHER
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
3 Years
Max Age
70 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2021-12-01
Primary Completion
2025-12-01
Completion
2026-12-01

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05126186 on ClinicalTrials.gov