RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem 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. Giving high-dose cyclophosphamide together with tacrolimus and mycophenolate mofetil after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well combination chemotherapy works when given together with a donor stem cell transplant, followed by tacrolimus, mycophenolate mofetil, and high-dose cyclophosphamide, in treating patients with high-risk hematologic cancer.
OBJECTIVES: Primary * To estimate the incidence of graft rejection and severe graft-versus-host disease after myeloablative HLA-mismatched peripheral blood stem cell transplantation (PBSCT) from first-degree relatives in patients with high-risk hematologic malignancies. Secondary * To estimate overall survival, relapse, non-relapse mortality, and event-free survival in these patients. * To characterize additional hematologic and non-hematologic toxicities of myeloablative haploidentical PBSCT. * To characterize donor hematopoietic chimerism in peripheral blood stem cells after PBSCT. OUTLINE: * Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -2, busulfan IV over 3 hours on days -7 to -4, and cyclophosphamide IV over 1-2 hours on days -3 and -2. * Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo infusion of unmanipulated peripheral blood stem cells on day 0. * Post-transplant regimen: Patients receive high-dose cyclophosphamide IV over 1-2 hours on days 3 and 4, tacrolimus IV over 24 hours or orally twice daily on days 5-180, and oral mycophenolate mofetil 3 times daily on days 5-34 followed by a taper to day 90. Treatment continues in the absence of disease progression or clinically significant graft-vs-host disease. After completion of PBSCT, patients are followed periodically for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
110 mg/m2 infused over 3 hours once daily on 4 consecutive days (Days -7, -6, -5, -4)
14.5 mg/kg infused over 1-2 hours once daily on 2 consecutive days (days -3,-2).
30mg/m2 infused over 30 minutes once daily on three consecutive days (days -5, -4, -3)
15 mg/kg po three times a daily with a maximum dose of 3gm/day starting D+5. To be discontinued on Day +35 in the absence of clinically significant GVHD.
0.03 mg/kg/day infuse over 24 hours starting on day +5 (adjusted to maintain trough level of 5-15 ng/ml). Switch to oral (twice daily divided dose) on day +21 or when able to tolerate PO. Discontinue on day +180 in the absence of clinically significant GVHD.
Patients to received unmanipulated PBSCs on Day 0
patients to receive unmanipulated PBSCs on day 0
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States
Incidence of Graft Rejection for Patients at Day 100
Number of patients who experienced graft rejection by Day 100
Time frame: Day 100
Number of Patients Who Experienced Severe Graft-versus-host Disease (GVHD)(Grade 3 or 4)
Number of patients who experienced post-transplant complication (GVHD) as seen by clinical evidence
Time frame: Day 100
Overall Survival at Day 100
Overall survival is assessed, without regard to disease status, post-transplant, at Day 100.
Time frame: Day 100
Non-relapse Mortality at 1 Year After Peripheral Blood Stem Cell Transplantation (PBSCT)
Non-relapse mortality refers to whether a patient dies of causes related to something other than the primary disease.
Time frame: 1 year
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 30 Post-transplantation
Chimerism analysis of peripheral blood mononuclear cells using PCR (polymerase chain reaction) for STR/VNTR (short tandme repeat/variable number tandem repeat) will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Time frame: Day 30
Non-relapse Mortality at Day 100 After Peripheral Blood Stem Cell Transplantation (PBSCT)
Time frame: Day 100
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 60 Post-transplantation
Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Time frame: Day 60
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 90 Post-transplantation
Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Time frame: Day 90
Overall Survival at 12 Months
Overall survival, defined as a patient being alive after transplant, is without regard to disease status.
Time frame: 12 months
Disease Free Survival at 12 Months
Disease free survival refers to patients with no evidence of disease after transplant, at the 12 month time point.
Time frame: 12 months
Disease Free Survival at Day 100
Disease free survival refers to patients with no evidence of disease after transplant, at the Day 100 time point.
Time frame: Day 100
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