Treatment of Graft Failure After Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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This is a guideline for the treatment of graft failure after hematopoietic stem cell transplant (HSCT). This regimen, consisting of cyclophosphamide and fludarabine with low dose total body irradiation (TBI) is designed to promote donor engraftment by day 42 after initial graft failure. The graft will consist of bone marrow or G-CSF mobilized peripheral blood from a haploidentical related donor. The source of stem cells will be determined by the transplant team based on factors such as patient's age, medical history, donor availability and will be according to the current University of Minnesota Blood and Marrow Transplantation Program selection guidelines.

Official Title
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Treatment of Graft Failure After Hematopoietic Stem Cell Transplantation

Conditions
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Primary Graft Failure, Secondary Graft Failure

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Cyclophosphamide
* Radiation: Total Body Irradiation
* Biological: Hematopoietic stem cell infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with primary or secondary graft failure, as defined below, may receive a second transplant: Primary graft failure is defined as not achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42 following the first transplant. Secondary graft failure is defined as achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42, but subsequently drops below 0.5x10^9/L without recovery. Loss of chimerism is defined as achieving an ANC ≥0.5x10^9/L for three consecutive, but with less than 10% CD15+ donor cells in the marrow or peripheral blood. Recipients should have acceptable organ function defined as: Renal: creatinine < 2.0 (adults) and creatinine clearance > 30. For creatinine clearance < 70, consultation with a BMT pharmacist is necessary for chemotherapy dose adjustments. Hepatic: bilirubin, AST/ALT, ALP < 10 x upper limit of normal Cardiac: left ventricular ejection fraction > 40% Exclusion Criteria: Uncontrolled infection at the time of transplant. Patients with Fanconi Anemia or other DNA breakage syndromes.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Treatment<br>This regimen consists of cyclophosphamide and fludarabine with low dose total body irradiation (TBI), followed by hematopoietic stem cell infusion. | Drug: Fludarabine<br>* Fludarabine 30 mg/m2 IV over 1 hour given on days -6 through -2 of transplant.<br>* Other names: Fludara;Drug: Cyclophosphamide<br>* Cyclophosphamide 14.5 mg/kg IV over 1-2 hours given on days -6 and -5 from transplant. And Cyclophosphamide 50 mg/kg IV over 2 hours given on days +3 and +4 from transplant.<br>Radiation: Total Body Irradiation<br>* TBI 200cGy in a single fraction on day -1 from transplant.<br>* Other names: TBI;Biological: Hematopoietic stem cell infusion<br>* Hematopoietic stem cell infusion given on day 0.<br>* Other names: HSCT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of donor engraftment | Rate of sustained donor engraftment at day 42 post this transplant. | day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of treatment related mortality | Rate of treatment related mortality (TRM) at day 100 | day 100 | 
| Rate of survival | Rate of survival by day 100. | Day 100 | 
| Rate of survival | Rate of survival at 1 year | 1 year | 
| Incidence of acute graft-versus-host disease | Incidence of acute graft-versus-host disease by day 100 | Day 100 | 
| Incidence of chronic graft-versus-host disease | Incidence of chronic graft-versus-host disease at 1 year. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic stem cell transplant