Clinical trial NCT00361140
Conditions: Myelodysplastic Syndromes Myeloproliferative Disorders Leukemia, Lymphocytic Myeloma Lymphoma
Keywords: Busulfan Fludarabine Chimerism Allogeneic stem cell transplantation (HCT) Myelodysplastic Syndromes Leukemia Myeloproliferative disorders (MPD) Leukemia, Lymphocytic Myeloma Lymphoma AUC Hematologic malignancies
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Start date: 2005-08-01; Completion date: 2012-02-01
Enrollment: 72 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Pre-transplant conditioning will include Fludarabine and dose-escalated Busulfan on days -6, -5, -4, and -3. Daily treatment doses will be adjusted to achieve target area under the plasma concentration time curve (AUC). Day 0 is the day of hematopoietic progenitor cell reinfusion. Supportive care will be based on institutional guidelines. Blood samples will be collected for dose modification based on the AUC levels. Dose escalation will proceed to determine the maximally tolerated level or AUC to evaluate the potential therapeutic benefit of higher doses of busulfan.

Detailed description:
Patients will receive anti-seizure prophylaxis beginning on day -7. Pre-transplant conditioning will include Fludarabine and dose-escalated Busulfan on days -6, -5, -4, and -3. Daily treatment doses will be adjusted to achieve target AUCs (area under the plasma concentration time curve). Day 0 is the day of hematopoietic progenitor cell reinfusion.

Supportive care will be based on institutional guidelines. In an effort to prevent hepatotoxicity, ursodiol will be given to patients. During chemotherapy patients will not receive concurrent metronidazole, itraconazole, or be given acetaminophen.

Blood samples will be collected at specific times after Dose 1 and Dose 4 and dose modification will be determined or based on the desired AUC levels. Doses 3 and/or 4 will be adjusted to achieve an average daily Busulfan AUC over the 4 treatment days.

Dose escalation will proceed through 3 dose levels to determine the maximally tolerated level or AUC to evaluate the potential therapeutic benefit of higher doses of busulfan.

Graft assessment, processing, and characterization will be done as per institutional guidelines. Donor-recipient chimerism (two genetically distinct types of blood cells) will be characterized by samples obtained pre-transplant and on days 30+/- 7, 90+/-7 and 360+/-30 post-transplant.

Arms: arm 1: Busulfan AUC Level 1: 6000 +/- 600 uM-min

Fludarabine 40mg/m2 IV over 1 hour arm 2: Busulfan AUC Level 2: 7500 +/- 750 uM-min

Fludarabine 40mg/m2 IV over 1 hour arm 3: AUC Level 3: 9000 +/- 900 uM-min

Fludarabine 40mg/m2 IV over 1 hour
Interventions: intervention 1: Busulfan intervention 2: Fludarabine
Intervention descriptions: intervention 1: Bu IV (BusulfexR) over 3 hours on days -6, -5, -4, and -3. Day -6 and -5 doses for patients on Level 1 will be 170mg/m2. This dose is based on the dose used by DeLima (2004) adjusted proportionately to achieve an AUC of 6000uM-min. Subsequent daily doses for patients on Level 1 will be adjusted to achieve an average AUC of 6000uM-min.

Day -6 and -5 doses for patients on Level 2 will be based on the mean dose required on Level 1 to achieve target AUC then adjusted proportionally for new target AUC.

Subsequent daily doses will be adjusted to achieve target AUCs. intervention 2: Fludarabine 40mg/m2 IV over 1 hour on days -6, -5, -4, and -3

Protocol documents: