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

NCT05126186 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: APHP200129
• Study Type: interventional
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief 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

Hematologic Diseases; Graft Failure; Allogeneic Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  at one year

Secondary Outcomes (54)

• Graft failure incidence

  at 3 months

• Neutrophils engraftment

  at day 100

• Platelets engraftment

  at day 100

• Absolute numbers of neutrophils

  at 1 month

• Absolute numbers of neutrophils

  at 2 months

Study Arms (1)

haplo-SCT with PTCy

EXPERIMENTAL

haploidentical (haplo) related donor Stem Cell Transplantation (haplo-SCT) 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)

Other: haplo-SCT with PTCy

Interventions

haplo-SCT with PTCy OTHER

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.

haplo-SCT with PTCy

Eligibility Criteria

• Age: 3 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged from 3 to 70 years
• All hematological diseases
• Suffering from primary or secondary (within the 60 days post-transplantation) graft failure after a 1st allo-SCT
• With usual criteria for allo-SCT:
• ECOG ≤ 2
• No severe and uncontrolled infection
• Cardiac function compatible with high dose of cyclophosphamide
• Adequate organ function: ASAT and ALAT ≤ 2.5N, total bilirubin ≤ 2N, creatinine clearance ≥30ml / min
• With identification of a haploidentical donor (brother, sister, parents, adult children or cousin)
• Absence of donor specific antibody (DSA) detected in the patient with a MFI ≥ 1500 (antibodies directed towards the distinct haplotype between donor and recipient)
• With health insurance coverage (bénéficiaire ou ayant droit).
• Understand informed consent or optimal treatment and follow-up.
• Contraception methods must be prescribed during all the duration of the research. Women and men of childbearing age must use contraceptive methods within 12 months and 6 months after the last dose of cyclophosphamide, respectively.
• Having signed a written informed consent (2 parents for patients aged less than 18)

You may not qualify if:

• Aged\< 3 years old and \>70 years old
• With uncontrolled infection
• With Seropositivity for HIV or HTLV-1 or active hepatitis B or C defined by a positive PCR HBV or HCV and associated hepatic cytolysis
• Yellow fever vaccine within 2 months before transplantation
• Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix)
• Uncontrolled coronary insufficiency, recent myocardial infarction \<6 month, current manifestations of heart failure, uncontrolled cardiac rhythm disorders, ventricular ejection fraction \<50%
• Heart failure according to NYHA (II or more)
• Preexisting acute hemorrhagic cystitis
• Renal failure with creatinine clearance \< 30ml / min
• Urinary tract obstruction
• Pregnant (β-HCG positive) or breast-feeding
• Who have any debilitating medical or psychiatric illness, which preclude understanding the inform consent as well as optimal treatment and follow-up
• COVID vaccination or recent COVID disease \<3 months
• Tutorship or curatorship
• Contraindications to treatments used during the research

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Hematologic Diseases

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Central Study Contacts

Régis Peffault de Latour

CONTACT

+33142385073; regis.peffaultdelatour@aphp.fr

Matthieu Resche-Rigon

CONTACT

+33142499742; matthieu.resche-rigon@u-paris.fr

Study Design

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

Study Record Dates

• First Submitted: November 8, 2021
• First Posted: November 18, 2021
• Study Start: December 1, 2021
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 18, 2021

Record last verified: 2021-11