Donor Stem Cell Transplant Followed by Cyclophosphamide in Treating Patients With Hematological Diseases

Study Overview
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Brief Summary
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This pilot clinical trial studies donor stem cell transplant followed by cyclophosphamide in treating patients with hematological diseases. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving cyclophosphamide after the transplant may stop this from happening.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine if haploidentical stem cell transplant using post-transplant cyclophosphamide results in 60% or better disease free survival (DFS) at 12 months at our institution. SECONDARY OBJECTIVES: I. To determine the rate of acute and chronic graft-versus-host disease (GvHD), non-relapse mortality, and relapse. OUTLINE: PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) once daily (QD) on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2 TRANSPLANT: Patients undergo stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35. After completion of study treatment, patients are followed up periodically for 2 years.

Official Title
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Haploidentical Stem Cell Transplant Using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot Study

Conditions
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Graft Versus Host Disease, Hematopoietic/Lymphoid Cancer

Intervention / Treatment
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* Drug: fludarabine phosphate
* Drug: busulfan
* Drug: cyclophosphamide
* Procedure: allogeneic hematopoietic stem cell transplantation
* Drug: tacrolimus
* Drug: mycophenolate mofetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of a hematological malignancy requiring an allogeneic stem cell transplant consistent with the standard of care Remission of any acute hematologic malignancy or adequate disease control for chronic malignancies. Ages 18-69 years old. Available familial haploidentical (4 to 6 out of 8 HLA loci-matched) donor Exclusion Criteria: Significant organ dysfunction defined as: LV EF < 50% (evaluated by echocardiogram or MRI), DLCO or FEV1 < 65% predicted, AST/ALT > 2.5 x ULN, Bilirubin > 1.5 x ULN, Serum creatinine > 2mg/dL, dialysis, or prior renal transplant HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation) Positive pregnancy test for women of childbearing age. Major anticipated illness or organ failure incompatible with survival form transplant. Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 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: Treatment (stem cell transplant with GVHD prophylaxis)<br>PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV QD on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2 TRANSPLANT: Patients undergo stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35. Allogeneic hematopoietic stem cell transplantation | Drug: fludarabine phosphate<br>* Given IV<br>* Other names: Fludara;Drug: busulfan<br>* Given IV<br>* Other names: Myeloleukon;Drug: cyclophosphamide<br>* Given IV<br>* Other names: Endoxana;Procedure: allogeneic hematopoietic stem cell transplantation<br>* Undergo myeloablative or reduced intensity allogeneic stem cell transplant<br>Drug: tacrolimus<br> <br> * Other names: Prograf;Drug: mycophenolate mofetil<br> <br> * Other names: MMF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12 Month Disease Free Survival Probability | The percentage of patients who experience death or disease relapse by one year will be calculated and a corresponding 95% confidence interval will be constructed using the normal approximation for binomial proportions. The survival function will be estimated and plotted using the method of Kaplan and Meier. | At 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Acute GvHD | Kaplan-Meier estimation of the rate of acute GvHD in the study population at one year with a 95% confidence interval. | 12 months | 
| Overall Survival | The survival function will be estimated and plotted using the method of Kaplan and Meier. | At 12 months | 
| Progression Free Survival | Kaplan-Meier estimation of the percentage of patients who are alive without progressive disease at one year. | At 12 months | 
| Relapse-free Mortality | Non-relapse mortality will be defined as time from registration to death due to anything other than relapse of hematological malignancy. Patients who relapse will be treated as a competing risk. | At 12 months |