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Not yet recruitingNCT05126186HaploRescueUpdated Nov 18, 2021

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

A Phase 2 interventional study of haplo-SCT with PTCy in Hematologic Diseases, Graft Failure and Allogeneic Hematopoietic Stem Cell Transplantation, sponsored by Assistance Publique - Hôpitaux de Paris. Not yet recruiting. Open to participants aged 3 Years to 70 Years. Per ClinicalTrials.gov, last updated 2021-11-18.

Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 2, Interventional, and Other

From the registry’s dates

  • Primary completion was expected by Dec 2025, 10 months ago, but the record still lists the study as not yet recruiting.
Phase
Phase 2
Study type
Interventional
Enrollment
35
Allocation
Not applicable
Ages
3 Years to 70 Years
Sex
All
01

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.

02

Conditions studied

  • Hematologic Diseases
  • Graft Failure
  • Allogeneic Hematopoietic Stem Cell Transplantation

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03

In context

Hematologic Diseases

460 studies on the registry are indexed under Hematologic Diseases; 105 are open to participants now.

This study's planned enrollment of 35 is below the median of 50 across 274 interventional studies indexed under Hematologic Diseases.

Browse Hematologic Diseases studies →

Lead sponsor

Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
3 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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)

Exclusion criteria

Exclusion Criteria:

  • 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
05

Study design

Phase
Phase 2
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
35 participants (estimated)

Study arms

  • Experimental
    haplo-SCT with PTCy

    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

  • Otherhaplo-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.

06

What researchers measure

Primary outcomes

  1. Overall Survival

    Time frame: at one year

Secondary outcomes

  1. Graft failure incidence

    Time frame: at 3 months

  2. Neutrophils engraftment

    3 consecutive days with neutrophiles \>0.5 G/L

    Time frame: at day 100

  3. Platelets engraftment

    7 consecutive days with platelets \>20 G/L

    Time frame: at day 100

  4. Absolute numbers of neutrophils

    Time frame: at 1 month

  5. Absolute numbers of neutrophils

    Time frame: at 2 months

  6. Absolute numbers of neutrophils

    Time frame: at 3 months

  7. Absolute numbers of neutrophils

    Time frame: at 6 months

  8. Absolute numbers of neutrophils

    Time frame: at 12 months

  9. Absolute numbers of neutrophils

    Time frame: through study completion, an average of 6 months

  10. Absolute number of platelets

    Time frame: at one month

  11. Absolute number of platelets

    Time frame: at 2 months

  12. Absolute number of platelets

    Time frame: at 3 months

  13. Absolute number of platelets

    Time frame: at 6 months

  14. Absolute number of platelets

    Time frame: at 12 months

  15. Absolute number of platelets

    Time frame: through study completion, an average of 6 months

  16. Incidence of use of growth factors for poor hematopoietic reconstitution

    Time frame: at 3 months

  17. Acute GvHD incidence

    Time frame: at 3 months

  18. Chronic GvHD incidence

    Time frame: at 24 months

  19. Relapse incidence

    Time frame: at 12 months

  20. Relapse incidence

    Time frame: at 24 months

  21. Progression free survival

    Time frame: at 12 months

  22. Progression free survival

    Time frame: at 24 months

  23. Incidence of CMV infection

    Time frame: at 12 months

  24. Incidence of EBV infection

    Time frame: at 12 months

  25. Incidence of severe infections

    Severe infections are defined as CTAE grade of 3 or 4

    Time frame: at 3 months

  26. Incidence of severe infections

    Severe infections are defined as CTAE grade of 3 or 4

    Time frame: at 6 months

  27. Incidence of severe infections

    Severe infections are defined as CTAE grade of 3 or 4

    Time frame: at 12 months

  28. Incidence of severe infections

    Severe infections are defined as CTAE grade of 3 or 4

    Time frame: at 24 months

  29. Incidence of veino-occlusive disease (VOD)

    Time frame: at 3 months

  30. Severity of veino-occlusive disease (VOD)

    Time frame: at 3 months

  31. Non-relapse mortality

    Time frame: at 24 months

  32. Incidence of cardiac toxicities

    Time frame: at 12 months

  33. Overall survival

    Time frame: at 24 months

  34. Interval between first allo-SCT and rescue haplo-SCT

    Time frame: at 60 days

  35. Quality of life for adults

    Quality of life will be assessed for adults using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Time frame: at 3 months

  36. Quality of life for adults

    Quality of life will be assessed for adults using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Time frame: at 6 months

  37. Quality of life for adults

    Quality of life will be assessed for adults using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Time frame: at 12 months

  38. Quality of life for adults

    Quality of life will be assessed for adults using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Time frame: at 24 months

  39. Quality of life for minors

    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning

    Time frame: at 3 months

  40. Quality of life for minors

    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning

    Time frame: at 6 months

  41. Quality of life for minors

    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning

    Time frame: at 12 months

  42. Quality of life for minors

    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning

    Time frame: at 24 months

  43. Proportion of patients with a donor chimerism of 90% or more

    Time frame: at 1 month

  44. Proportion of patients with a donor chimerism of 90% or more

    Time frame: at 3 months

  45. Proportion of patients with a donor chimerism of 90% or more

    Time frame: at 6 months

  46. Proportion of patients with a donor chimerism of 90% or more

    Time frame: at 12 months

  47. Immune reconstitution

    Immune reconstitution will be defined by analyzing T, B, NK, regulatory T cell levels in the peripheral blood

    Time frame: at 3 months post-transplantation

  48. Immune reconstitution

    Immune reconstitution will be defined by analyzing T, B, NK, regulatory T cell levels in the peripheral blood

    Time frame: at 6 months post-transplantation

  49. Immune reconstitution

    Immune reconstitution will be defined by analyzing T, B, NK, regulatory T cell levels in the peripheral blood

    Time frame: at 12 months post-transplantation

  50. Immune reconstitution

    Immune reconstitution will be defined by analyzing T, B, NK, regulatory T cell levels in the peripheral blood

    Time frame: at 24 months post-transplantation

  51. Iron overload estimation

    Time frame: at 3 months

  52. Iron overload estimation

    Time frame: at 6 months

  53. Iron overload estimation

    Time frame: at 12 months

  54. Iron overload estimation

    Time frame: at 24 months

07

Study locations

No study locations are listed for this record.

08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 18, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05126186
Lead sponsor
Assistance Publique - Hôpitaux de Paris
Responsible party
Sponsor
First posted
Nov 18, 2021
Start date
Dec 1, 2021 (estimated)
Primary completion
Dec 1, 2025 (estimated)
Completion
Dec 1, 2026 (estimated)
Last update
Nov 18, 2021

Study contacts

Régis Peffault de Latour
Contact
regis.peffaultdelatour@aphp.fr
+33142385073
Matthieu Resche-Rigon
Contact
matthieu.resche-rigon@u-paris.fr
+33142499742

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Nov 2021. You cannot join it, but the record below documents what was studied.

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