Phase 2 Haplotype Mismatched HSCT in Patients With Hematological Malignancies

Study Overview
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Brief Summary
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The purpose of this study is to determine if haplotype-mismatched HSCT is associated with an improvement in treatment-related mortality (TRM) rate at 6 months.

Official Title
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A Phase II Trial of Haplotype Mismatched Hematopoietic Stem Cell Transplantation Using Highly Purified CD34 Cells in Patients With Hematological Malignancies

Conditions
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Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplasia, Chronic Myeloid Leukemia

Intervention / Treatment
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* Radiation: Total Body Irradiation
* Drug: Thiotepa
* Drug: Fludarabine
* Biological: Rabbit ATG
* Drug: Palifermin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically documented AML, ALL, MDS, CML, Acute myeloid leukemia (AML) with one or more of the following criteria CR 1 with poor risk features CR 2, or higher order CR Acute lymphoblastic leukemia (ALL) with one of the following criteria CR 1 with poor risk features CR 2, or higher order CR Myelodysplasia, RAEB I Donor has been identified Age ≤ 65 years. Performance Status 0-1. Exclusion Criteria: Patients relapsing <6 months after autologous SCT are not eligible. Patients with active infections requiring oral or intravenous antibiotics are not eligible for enrollment until resolution of infection. Non-pregnant and non-nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Total body Irradiation; Thiotepa; Fludarabine; Rabbit ATG; | Radiation: Total Body Irradiation<br>* 8 Gy on Day -9<br>Drug: Thiotepa<br>* 5 mg/kg/d on Day -8 to -7<br>Drug: Fludarabine<br>* 40 mg/m2/d on Day -6 to -3<br>Biological: Rabbit ATG<br>* 2.5 mg/kg/d on Day -5 to -2<br>* Other names: Thymoglobulin;|
| Experimental: 2<br>Palifermin; Total Body Irradiation; Thiotepa; Fludarabine; Rabbit ATG | Radiation: Total Body Irradiation<br>* 8 Gy on Day -9<br>Drug: Thiotepa<br>* 5 mg/kg/d on Day -8 to -7<br>Drug: Fludarabine<br>* 40 mg/m2/d on Day -6 to -3<br>Biological: Rabbit ATG<br>* 2.5 mg/kg/d on Day -5 to -2<br>* Other names: Thymoglobulin;Drug: Palifermin<br>* 60 ug/kg (actual body weight) on Day -9 to -7 and Day 0 to +2<br>* Other names: Kepivance;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related Mortality (TRM) Rate at 6 Months After Transplantation | To determine if haplotype-mismatched HSCT is associated with a ≤40% treatment-related mortality (TRM) rate at 6 months after transplantation; a TRM ≥60% being considered unacceptable. The percent of patients with the exact 95% confidence interval who had treatment-related mortality within 6 months of their transplant is presented. | thru 6 months after transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regimen-related Toxicity | The number of unique patients who had adverse events that were possibly/probably/definitely related to treatment/regimen. | Up to 1 year | 
| Time to Neutrophil Engraftment | Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophil is defined as the time from transplant until absolute neutrophil count (ANC) > 500 uL for 3 consecutive days. The median and 95% confidence intervals will be provided. | Transplant (Day 0) up to 1 year | 
| Time to Platelet Engraftment | Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of seven consecutive days after transplantation during which the platelet count is at least 20 x109/l without transfusion support. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided. | Transplant (Day 0) up to 1 year | 
| Acute Graft vs. Host Disease (GvHD) | Number of unique patients who had acute Graft vs. Host Disease (GvHD) diagnosed while on the study. | Up to 1 year | 
| Chronic Graft vs. Host Disease (GvHD) | Number of unique patients who had chronic Graft vs. Host Disease (GvHD) diagnosed while on the study. | Up to 1 year | 
| Frequency of Infection | Number of unique patients with bacterial and/or viral infections reported. | Day 0 through 1 year post transplantation |