Haploidentical Hematopoietic Stem Cell Transplantation for Acute Leukemias

Study Overview
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Brief Summary
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This is a prospective observational cohort study of haploidentical transplantation with post-transplant cyclophosphamide for acute leukemias using reduced intensity conditioning for acute myeloid leukemia (AML) and myeloablative conditioning for acute lymphoblastic leukemia (ALL).

Detailed Description
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Hematopoietic stem cell transplantation (HSCT) is the most effective treatment for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), with the lowest rates of relapse. Fertility rate in Brazil is falling, and only 25% of people born today will have a matched sibling donor. On the other hand, currently donor non-related to about 50% of patients enrolled in Brazilian Receptor Registry (REREME). Consequently, at least 35% of patients won't have a matched donor. The haploidentical transplantation is defined as a partially matched hematopoietic cell transplantation, using a partially matched family donor (parent, sibling or child). Haploidentical transplantation activity is growing worldwide, with results comparable matched unrelated donors. The objective of this study is to test the feasibility of haploidentical transplantation with post transplant cyclophosphamide for acute leukemias in a Brazil.

Official Title
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Haploidentical Hematopoietic Stem Cell Transplantation for Acute Leukemias

Conditions
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Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention / Treatment
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* Procedure: Haploidentical Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute lymphoblastic leukemia or acute myeloid leukemia Exclusion Criteria: Severe comorbidities Second transplant

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 60 Years

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 |
| --- | --- |
| Group A: Acute Lymphoblastic Leukemia<br>Haploidentical Stem Cell Transplantation with Post Transplant Cyclophosphamide (PTCy) Preferred conditioning: Total Body Irradiation 1200 cGy (TBI1200) + Fludarabine 120 mg/m2 (Flu120) Alternative conditionings: Melphalan 100-140 mg/m2 (Mel100-140) + Fludarabine 160 mg/m2 (Flu160) + Total Body Irradiation 200 cGy (TBI200) Busulfan 9.6 mg/kg (Bu9.6) + Fludarabine 150 mg/m2 (Flu150) + TBI200 Graft versus host disease Prophylaxis: Post-Transplant Cyclophosphamide (PTCy) + Tacrolimus (FK) or Cyclosporin (CSA) + Mycophenolate Mofetil (MMF) | Procedure: Haploidentical Stem Cell Transplantation<br>* Haploidentical Stem Cell Transplantation from a related donor (partially matched sibling, father, mother, son or daughter).<br>|
| Group B: Acute Myeloid Leukemia<br>Haploidentical Stem Cell Transplantation with Post Transplant Cyclophosphamide (PTCy) Preferred Conditioning: Mel100-140 + Flu160 + TBI200 Alternative conditionings: Bu9,6 + Flu150 + TBI200 Cyclophosphamide 29 mg/kg + Flu150 + TBI200 Graft versus host disease Prophylaxis: PTCy + FK or CSA + MMF | Procedure: Haploidentical Stem Cell Transplantation<br>* Haploidentical Stem Cell Transplantation from a related donor (partially matched sibling, father, mother, son or daughter).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | 1-year overall survival. Survival curves will be estimated by Kaplan-Meier methodology. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of leukemia relapse | Relapse will be defined by reappearance of Leukemic Cells in bone marrow (>5%) or peripheral blood (>1%). Risk factors for leukemia relapse will be estimated by extended Cox Model for competing risks (Fine & Gray model). Competing event will be defined as death in remission. | 5 years | 
| Transplant Related Mortality | Transplant-related mortality (TRM) will be defined as death in remission. Risk factors for TRM will be estimated by extended Cox Model for competing risks (Fine & Gray model). Competing event will be defined as leukemia relapse. | 6 months | 
| Cumulative Incidence of acute Graft Versus Host Disease | Acute graft versus host disease will be diagnosed and graded by modified Glucksberg criteria. Risk factor for acute graft versus host disease will be estimated by extended Cox Model for competing risks (Fine & Gray model). Cumulative incidence curves will be estimated by Gray methodology. | 5 years | 
| Cumulative Incidence of chronic Graft Versus Host Disease | Chronic graft versus host disease will be diagnosed and graded by National Institute of Health Consensus (NIH Consensus). Risk factor for chronic graft versus host disease will be estimated by extended Cox Model for competing risks (Fine & Gray model). Cumulative incidence curves will be estimated by Gray methodology. | 5 years | 
| Cumulative Incidence of Infectious Complications | Cumulative incidence of viral, fungal and bacterial infections. Subgroups will be compared by Cox Model for competing risks (Fine & Gray model). Cytomegalovirus reactivation will be analyzed by multiple events Cox Model. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Haploidentical Hematopoietic Stem Cell Transplantation, Partially Matched Hematopoietic Stem Cell Transplantation, Post-transplant Cyclophosphamide, Hematopoietic Stem Cell Transplantation