Conditioning Treatment With Umbilical Cord Blood Transplant for Hematologic Malignancies

Study Overview
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Brief Summary
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This is a phase II study to assess the day 180 event free and overall survival after administration of a specified combination of fludarabine, busulfan, Total Body Irradiation (TBI), and thymoglobulin reduced intensity conditioning and 2 unit UCB stem cell transplant in a single institution setting in patients with hematologic malignancies for whom allogeneic transplantation is indicated.

Official Title
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Phase II Trial of Reduced Intensity Conditioning (RIC) and Allogeneic Transplantation of Umbilical Cord Blood (UCB) From Unrelated Donors in Patients With Hematologic Malignancies

Conditions
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Hematologic Malignancies

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Busulfan
* Drug: Thymoglobulin
* Radiation: Total Body Irradiation
* Biological: Umbilical Cord Blood


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects 18-70 years old. ECOG 0-2 Patients must have a diagnosis of one of the following: Chronic Myeloid Leukemia Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Hodgkin's Disease Non-Hodgkins Lymphoma Myelodysplastic Syndromes Myeloproliferative Disorder Patients must have adequate visceral organ function Patients must furnish written informed consent and HIPAA authorization for release of personal health information. Patients must be able to understand the requirements of the study, abide by the study restrictions, and agree to return for the required assessments. Exclusion Criteria: Patients who have a histocompatible sibling-matched donor age 18 to 65 years in good health who is willing to donate stem cells are ineligible. Patients who are pregnant are ineligible. Patients are ineligible if they have received cumulative chemotherapy doses in excess of: carmustine (BCNU) 400 mg/m2, and/or a cumulative anthracycline exposure in excess of 550 mg/m2 doxorubicin (Adriamycin®) unless gated-pool radionuclide cardiac scan shows greater than/equal to 45% ejection fraction. Patients who are HIV or HTLV-I, -II antibody sero-positive are ineligible.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced Intensity Conditioning with UCB Transplant<br> | Drug: Fludarabine<br>* 35 mg/m2 IV/day x 5 days<br>Drug: Busulfan<br>* .8 mg/kg IV Q6h x 8 doses<br>Drug: Thymoglobulin<br>* 1.5 mg/kg/day x 3 days<br>Radiation: Total Body Irradiation<br>* 150 cGy for 2 days<br>Biological: Umbilical Cord Blood<br>* Two partially HLA-matched UCB units. Each unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event Free Survival | Number of subjects surviving with no events at 180 days post transplantation (Day 0). | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant Engraftment | Number of patients with successful UCB engraftment. | Day 42 | 
| Incidence of Graft-versus-host disease (GVHD) | Number of patients that experience acute or chronic GVHD. | 1 year | 
| Time course for peripheral blood chimerism. | Percent of patients with >95% donor chimerism. | 56 days | 
| Incidence of secondary lymphoproliferative diseases | Number of patients with secondary lymphoproliferative diseases. | 6 months | 
| Incidence of disease recurrence | Number of patients experience disease recurrence. | Up to two years | 
| Incidence of serious infectious complications | Number of patients experiencing serious infectious complications. | 1 year | 
| Overall Survivals | Number of patient with overall event free survival and overall survival distributions. | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Myeloid Leukemia, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Non-Hodgkins Lymphoma, Hodgkin's Disease, Myelodysplastic Syndromes, Myeloproliferative Disorder