Safety and Efficacy of ProHema Modulated Umbilical Cord Blood Units in Subjects With Hematologic Malignancies.

Study Overview
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Brief Summary
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The purpose of this research study is to determine the safety and efficacy of a reduced intensity conditioning regimen during a double umbilical cord blood unit transplant with one of the cord blood units modulated with ProHema.

Detailed Description
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The purpose of this research study is to determine the safety and efficacy of a reduced intensity conditioning regimen during a double umbilical cord blood unit transplant with one of the cord blood units modulated with ProHema. -As part of this research study cord units will be modulated in the laboratory with ProHema before it is given to the participant. Two different treatment groups will be tested. Group 1: will have the second cord blood unit modulated with ProHema; Group 2: will have the first cord blood unit modulated with ProHema.

Official Title
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A Phase I Study of Reduced Intensity, Sequential Double Umbilical Cord Blood Transplantation Using ProHema Modulated Umbilical Cord Blood Units in Subjects With Hematological Malignancies.

Conditions
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Hematologic Malignancies, Allogeneic Stem Cell Transplantation

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Melphalan
* Drug: Antithymocyte Globulin
* Drug: Sirolimus
* Drug: Tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with hematologic malignancies for whom allogeneic stem cell transplantation is deemed clinically appropriate Patient must be ineligible for traditional myeloablative transplantation according to treating physician Lack of 6/6 or 5/6 HLA-matched related, 8/8 HLA-matched unrelated donor, or unrelated donor not available within a time frame necessary to perform a potentially curative stem cell transplant 18-65 years of age ECOG Performance Status 0-2 Exclusion Criteria: The following hematologic malignancies are excluded: Myelofibrosis unless there has been exposure to cytotoxic chemotherapy for the treatment of progression to acute myeloid leukemia Chronic Myelogenous Leukemia, unless there has been exposure to cytotoxic chemotherapy for the treatment of blast phase, 3) Aplastic anemia, in the absence of transformation to Myelodysplastic disorder Cardiac disease: symptomatic congestive heart failure or evidence of left ventricular dysfunction as measured by gated radionucleotide ventriculogram or echocardiogram; active angina pectoris, or uncontrolled hypertension Pulmonary disease: symptomatic chronic obstructive lung disease, symptomatic restrictive lung disease, or corrected DLCO of < 50% of predicted, corrected hemoglobin Renal disease: serum creatinine > 2.0mg/dl Hepatic disease: serum bilirubin > 2.0mg/dl (expect in the case of Gilbert's syndrome or ongoing hemolytic anemia), SGOT or SGPT > 3 x upper limit of normal Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation HIV antibody Uncontrolled infection Pregnancy or breast feeding mother Inability to comply with the requirements for care after allogeneic stem cell transplantation

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: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>2 umbilical cord units: Second cord blood unit modulated with ProHema | Drug: Fludarabine<br>* 30mg/m2/day IV x 6 days<br>Drug: Melphalan<br>* 100 mg/m2/day IV x 1 day<br>Drug: Antithymocyte Globulin<br>* 1mg/kg/day x 4 days<br>Drug: Sirolimus<br>* GVHD Prophylaxis: Target range 3-12 ng/ml<br>Drug: Tacrolimus<br>* GVHD Prophylaxis: Target range 5-10 ng/ml<br>|
| Active Comparator: Group 2<br>2 umbilical cord units: First cord blood unit modulated with ProHema | Drug: Fludarabine<br>* 30mg/m2/day IV x 6 days<br>Drug: Melphalan<br>* 100 mg/m2/day IV x 1 day<br>Drug: Antithymocyte Globulin<br>* 1mg/kg/day x 4 days<br>Drug: Sirolimus<br>* GVHD Prophylaxis: Target range 3-12 ng/ml<br>Drug: Tacrolimus<br>* GVHD Prophylaxis: Target range 5-10 ng/ml<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the safety of ProHema modulated umbilical cord blood units when used for transplantation in a reduced intensity, sequential umbilical cord blood transplantation model. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to engraftment of umbilical cord blood units |  | 2 years | 
| Fractional chimerism of transplanted cord blood units |  | 2 years | 
| Rates of acute and chronic GVHD |  | 2 years | 
| 30- and 100-day treatment related mortality |  | 2 years | 
| Measures of immune reconstitution and relapse-free and overall survival at 1 and 2 years after transplantation |  | 2 years |