Cord Blood Transplantation for Patients With Cancer

Study Overview
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Brief Summary
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The primary objective of this study is to assess the rate of engraftment with combined haploidentical-cord blood transplantation in patients with pre-existing donor specific antibodies and in those with active disease.

Detailed Description
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Primary Objective - To assess the rate of engraftment with combined haploidentical-cord blood transplantation in patients with pre-existing donor specific anti-HLA antibodies and in those with active disease Secondary Objectives To determine the long term fate of the haplo transplant and the cord blood transplant in this setting. To describe the incidence and severity of acute and chronic GVHD.

Official Title
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Combined Transplantation of Unmanipulated Haploidentical and a SingleCord Blood Unit for Patients With Hematologic Malignancies

Conditions
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Hematological Disease

Intervention / Treatment
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* Drug: Melphalan
* Drug: Fludarabine
* Drug: Antithymocyte Globulin (ATG)
* Drug: Busulfan
* Drug: Total Body Irradiation (TBI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory acute leukemia (myeloid or lymphoid) Acute leukemia in first remission at high-risk for recurrence Chronic myelogenous leukemia in accelerated phase or blast-crisis Chronic myelogenous leukemia in chronic phase Recurrent or refractory malignant lymphoma or Hodgkin lymphoma Chronic lymphocytic leukemia, relapsed or with poor prognostic features Multiple myeloma Myelodysplastic syndrome Chronic myeloproliferative disease Hemoglobinopathies Aplastic anemia Exclusion Criteria: Zubrod performance status > 2 Life expectancy is severely limited by concomitant illness Patients with severely decreased LVEF or impaired pulmonary function tests Estimated Creatinine Clearance <50 ml/min Serum bilirubin> 2.0 mg/dl or SGPT >3 x upper limit of normal Evidence of chronic active hepatitis or cirrhosis HIV-positive Patient is pregnant Patient or guardian not able to sign informed consent

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conditioning Regimen I<br>Arm I contains fludarabine, melphalan, and antithymocyte globulin (ATG) | Drug: Melphalan<br>* Melphalan is given daily for 2 days, overlapping with the completion of fludarabine.<br>* Other names: Sarcolysin;Drug: Fludarabine<br>* Fludarabine is given through the vein daily for 5 days.<br>* Other names: Fludara;Drug: Antithymocyte Globulin (ATG)<br>* ATG is given every other day for 4 days.<br>|
| Experimental: Conditioning Regimen II<br>Arm II contains fludarabine, busulfan, antithymocyte globulin (ATG), and total body irradiation (TBI). | Drug: Fludarabine<br>* Fludarabine is given through the vein daily for 5 days.<br>* Other names: Fludara;Drug: Antithymocyte Globulin (ATG)<br>* ATG is given every other day for 4 days.<br>Drug: Busulfan<br>* Busulfan is given daily for 4 days.<br>* Other names: Busulfex IV;Drug: Total Body Irradiation (TBI)<br>* TBI is given twice on the last day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cord Blood Engraftment by Day 100 | Percent of subjects with cord blood engraftment on or before day 100. Detectable cord blood engraftment should be present by day 100 in at least 50% of patients. As of 44 days post-transplant, only haploidentical donor chimerism achieved in the one patient enrolled in the Fludarabine, melphalan, and ATG arm. There were no cord cells detected for this patient. | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at Day 100 | Percent of subjects who are alive 100 days after the stem cell infusion | 100 days |