In-Vivo Activated T-Cell Depletion to Prevent GVHD

Study Overview
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Brief Summary
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The purpose of this study is to compare the effects (good and bad) of the medication basiliximab in combination with cyclosporine with cyclosporine alone for the prevention of graft-versus-host disease. This research is being done because there is no completely safe and effective prevention for graft-versus-host disease. It is known that cyclosporine helps with GVHD but we would like to know if the addition of basiliximab will decrease the incidence and/or severity of GVHD after a transplant known as nonmyeloablative (mini transplant).

Official Title
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In-Vivo Activated T-Cell Depletion to Prevent GVHD

Conditions
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Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Chronic Lymphocytic Leukemia, Myelodysplasia, Lymphoma, Non-Hodgkin's, Mantle-Cell Lymphoma, Hodgkin's Disease, Multiple Myeloma, Myelofibrosis

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: Cyclosporine
* Drug: Mycophenolate mofetil
* Drug: Basiliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute myelogenous leukemia, Acute lymphocytic leukemia, Chronic myelogenous leukemia, Chronic lymphocytic leukemia, Myelodysplasia, Non-Hodgkin's Lymphoma, Mantle cell, Hodgkin's Disease, Multiple Myeloma, Myelofibrosis with disease-specific eligibility requirements as outlined in the protocol Donor Requirement: Must have a fully HLA-matched (10 of 10) related or unrelated donor, eighteen years of age or older, who is capable of undergoing GCSF mobilization and apheresis. Exclusion Criteria: Active CNS disease (the presence of leukemic blasts in the CSF) Pregnancy or breast-feeding SGOT >3x upper limit of normal Creatinine >2 or creatinine clearance <50cc/hr. Fractional shortening by echocardiogram not within normal limits per institution Pulmonary function: DLCO less that 50% of normal predicted, corrected for anemia Prior allogeneic transplant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cyclophosphamide|60mg/kg/day for two consecutive days (-7,-6).|
|Drug: Fludarabine|25mg/m2/day for 5 consecutive days|
|Drug: Cyclosporine|3mg/kg/day will be given by continuous intravenous infusion beginning on Day -1.|
|Drug: Mycophenolate mofetil|1000 mg will be administered through day +60 and then discontinued if there is no GVHD.|
|Drug: Basiliximab|20mg , will be given by intravenous infusion (without an in-line filter) over at least 15 minutes beginning 3 days after engraftment.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Acute Grade II-IV GVHD | Number of patients with Grade II-IV GVHD according to NMDP/CIBMTR GVHD severity scale. This scale measures the degree of GVHD involvement in the patient's skin (inflammatory skin disease), liver (bilirubin levels) and intestinal tract (amount of diarrhea) as well as the level of decline in a patient's activity and physical abilities. | until 30 days after stem cell transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Engrafting at Day +30 by Short Tandem Repeat (STR) on Peripheral Blood Mononuclear Cells (PBMC's). |  | until 30 days after stem cell transplant | 
| Number of Days for Absolute Neutrophil Count to Recover | Average number of day per patient for absolute neutrophil count to recover(> 500/mm3 for 3 consecutive days). | From Day -1 (day before stem cell infusion) to Day+20 (20 days after stem cell infusion) | 
| Time to Resolution of Cytopenias: Platelet Transfusion Independence | Average number of days per patient for resolution of cytopenias. | From Day -1 (day before stem cell infusion) to Day +20 (20 days after stem cell infusion) | 
| Patients Who Experience Serious Transplant Related Toxicities as Evaluated by Bone Marrow Transplant-adjusted NCI Common Toxicity Criteria. | Number of patients who died due to transplant related toxicities | up to 2 years after stem cell transplant |