RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer and abnormal 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 cyclophosphamide, mycophenolate mofetil, or tacrolimus after transplant may stop this from happening. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with tacrolimus and mycophenolate mofetil works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.
OBJECTIVES: Primary * Determine the optimal dose of post-transplant immunosuppression comprising high-dose cyclophosphamide, tacrolimus, and mycophenolate mofetil administered after myeloablative conditioning chemotherapy comprising busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation in patients with high-risk hematologic malignancies. * Determine the incidence and severity of acute graft-versus-host disease in patients treated with this regimen. * Determine other toxic effects of this regimen in these patients. Secondary * Determine immune reconstitution in patients treated with this regimen. * Determine disease control in patients treated with this regimen. OUTLINE: This is a pilot study. Patients are stratified according to age (≤ 19 years old vs \> 19 years old). * Myeloablative conditioning chemotherapy: Patients receive busulfan IV or orally 4 times daily on days -7 to -4 OR days -6 to -3 and cyclophosphamide IV over 1 hour once daily on days -3 to -1 OR days -2 and -1. * Allogeneic bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0. * Immunosuppression therapy: Patients receive high-dose cyclophosphamide IV over 1 hour on days 3 and 4. After completion of study transplantation, patients are followed at 30 and 60 days, 6 months, 1 year, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
142
Days -7 to -4: 4 mg/kg PO daily OR 3.2 mg/kg IV daily OR 160 mg/m\^2 daily (for pediatric recipients)
Days -3, -2, +3, +4: 50 mg/kg IV daily
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Percentage of Participants Who Develop Acute Graft-versus-host Disease (GVHD)
Percentage of participants who developed grades II-IV and grades III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).
Time frame: Day 100
Days to Engraftment
Median number of days to neutrophil and platelet engraftment.
Time frame: Up to one year
Chimerism
Number of patients who achieved 100% donor chimerism.
Time frame: Day 30, Day 60
Non-relapse Mortality
Percentage of participants who died for BMT-related reasons.
Time frame: Day 100, 2 years
Relapse
Percentage of participants who developed relapse or progressive disease.
Time frame: 2 years
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