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

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

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.

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.

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.