Allogeneic Transplantation Using Timed Sequential Busulfan and Fludarabine Conditioning
Leukemia, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia
About this trial
This is an interventional treatment trial for Leukemia focused on measuring Leukemia, Acute myeloid leukemia, Acute lymphocytic leukemia, Chronic myeloid leukemia, Chronic lymphocytic leukemia, Myeloproliferative Diseases, Non-Hodgkins Lymphoma, Hodgkins lymphoma, Multiple myeloma, Myelodysplastic syndrome, MDS, Fludarabine monophosphate, Fludarabine phosphate, Fludara, Busulfan, Busulfex, Myleran, Tacrolimus, Prograf, Methotrexate, G-CSF, Filgrastim, Neupogen, Stem cell transplant, Allogeneic Transplantation
Eligibility Criteria
Inclusion Criteria:
- Patients with high-risk hematologic malignancies with anticipated poor prognosis with non transplant therapy, including those in remission or with induction failure and after treated or untreated relapse. Diagnoses to be included a) Acute myeloid leukemia; b) Acute lymphocytic leukemia; c) Chronic myeloid leukemia; d) Chronic lymphocytic leukemia; e) Myelodysplastic syndrome; f) Myeloproliferative syndromes; g) Non-Hodgkins lymphoma; h) Hodgkins Lymphoma; i) Multiple myeloma.
- Patients must have a histocompatible stem cell donor. An HLA-identical related donor or a 8/8 matched unrelated donor.
- Age 5 to 75 years old.
- Performance score of >/= 70 by Karnofsky/Lansky or PS 0 to 1 (ECOG </=1).
- Left ventricular ejection fraction at least 40%.
- Adequate pulmonary function with FEV1, FVC and DLCO >/=50% of expected corrected for hemoglobin and/or volume. Children unable to perform pulmonary function tests (e.g., less than 7 years old) pulse oximetry of >/= 92% on room air
- Creatinine clearance (calculated creatinine clearance is permitted) should be >40 ml/min.
- Bilirubin </= 2 x the upper limit of normal (except Gilbert's Syndrome). SGPT (ALT) < 200.
- Negative Beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use an effective contraceptive measure while on study.
- Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.
Exclusion Criteria:
- HIV seropositivity.
- Uncontrolled infections.
Sites / Locations
- University of Texas MD Anderson Cancer Center
Arms of the Study
Arm 1
Experimental
Fludarabine + Busulfan
Fludarabine administered by vein at dose of 40 mg/m2 in 100 ml of normal saline (NS) on Days -6 through -3. First two doses of Busulfan, 80 mg/m2 administered as an outpatient or as an inpatient to facilitate for this pharmacokinetically directed therapy. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic studies.