Busulfan Monotherapy as Conditioning for Autologous Hematopoietic Progenitor Cell Transplantation
- Conditions
- Acute Myeloid Leukemia (AML)
- Interventions
- Registration Number
- NCT00363467
- Brief Summary
During the pre-transplantation phase (following completion of consolidation chemotherapy), patients will begin to receive G-CSF at 10 mcg/kg twice daily; leukapheresis will also be given until a target goal for recipient body weight is obtained, or up to a maximum of 5 days. Conditioning/Preparative therapy will follow PBSC collection for up to 30 days with Busulfan IV daily x 4 days; subsequent doses will be adjusted based on pharmacokinetic (plasma level)monitoring. Following 1 day of rest, stem cell reinfusion will begin with supportive care. During follow-up, patients will be monitored out to 730 days.
- Detailed Description
1. Pre- Transplantation Phase -
1. Twenty-four to 48 hours following completion of consolidation chemotherapy, patients will begin to receive G-CSF at 10 mcg/kg twice daily subcutaneously. Alternatively, patients may receive G-CSF alone (same dose) as mobilization therapy.
2. Leukapheresis will begin day 4 of G-CSF administration and proceed according to institutional guidelines. Leukapheresis will continue until a target goal for recipient body weight is obtained, or up to a maximum of 5 days. A minimum recipient body weight is required to proceed to transplantation.
2. Transplantation Phase
a. Conditioning/Preparative therapy - up to 30 days following PBSC collection, patients will begin conditioning therapy with Busulfan IV daily x 4 days (transplantation days -5,-4,-3,-2). The day -5 and -4 dose will be 130mg/m2; subsequent doses will be adjusted based on pharmacokinetic monitoring.
* Busulfan plasma level monitoring, collected around the first dose of busulfan b. Stem cell reinfusion - following 1 day of rest, previously collected autologous peripheral blood stem cells will be infused.
* The administration of supportive measures (e.g. intravenous fluids, antihistamines) during stem cell reinfusion will be performed according to institutional guidelines.
3. Supportive care
1. Antibiotic prophylaxis- according to hospital/institutional guidelines, and at the discretion of the treating physician.
2. Growth factor support
3. Transfusion support
4. Prophylaxis for busulfan-induced seizures
4. During follow-up, patients will be seen at least weekly for the first month and there after periodically out to 730 days posttransplant. The following medical procedures will be done:
* Medical history and physical exam (including concurrent meds, vital signs, performance status and weight)
* Standard labs
* Bone marrow aspirate and biopsy
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
-
Patients must have had histologically confirmed diagnosis of AML, in 1st complete remission, by a pathologic review at the H. Lee Moffitt Cancer Center and Research Institute. Any induction/consolidation regimen is permitted.
-
General Inclusion Criteria:
- Age 56-74
- Able to give informed consent
- Hepatic and renal function: normal bilirubin, AST and ALT less than or equal to 2x normal limits, serum creatinine less than or equal to 1.5x normal
- Left ventricular ejection fraction (LVEF) must be in normal range
- FEV1 AND DLCO greater than or equal to 50% predicted (at planned time of transplantation)
- ECOG PS less than or equal to 2 (at planned time of transplantation)
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Disease Specific Inclusion Criteria:
- Adverse-risk karyotype (del 5/5q, 7/7q, 3q, greater than or equal to 3 abnormalities):
- Intermediate-risk karyotype [46 XY, +8, -Y, +6, or any other isolated (<3 total) non-random abnormality not included in the adverse-risk category or favorable-risk category below]
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AML arising from antecedent hematologic disorder (e.g. MDS)
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Secondary AML (t-AML)
- Acute Promyelocytic Leukemia(FAB M3) subtype
- Presence of (8;21) translocation or inversion 16/t(16;16) cytogenetic phenotype (i.e. favorable-risk AML)
- Eligible for and willing to undergo matched-sibling allogeneic transplantation
- Greater than 2 induction regimens required to achieve complete remission
- Duration of > 8 weeks between completion of induction chemotherapy and initiation of consolidation chemotherapy
- No prior malignancy is allowed, except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least 5 years.
- Prior extensive radiation therapy (>25% of bone marrow reserve)
- Concomitant radiation therapy, chemotherapy, or immunotherapy
- Intrinsic impaired organ function (as stated above)
- Active infection
- Positive serum pregnancy test in women who have not yet reached menopause (no menstrual periods for >12 months or who have not undergone tubal ligation or complete hysterectomy.
- Women who are breast-feeding
- Positive HIV testing
- Presence of CNS leukemia
- Uncontrolled insulin-dependent diabetes mellitus or uncompensated major thyroid or adrenal gland dysfunction
- Physical or psychiatric conditions that in the estimation of the PI or his designee place the patient at high-risk of toxicity or non-compliance
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Autologous Hematopoietic Progenitor Cell Transplantation Leukapheresis G-CSF Mobilization Leukepheresis Busulfan Stem Cell Reinfusion Autologous Hematopoietic Progenitor Cell Transplantation Stem cell reinfusion G-CSF Mobilization Leukepheresis Busulfan Stem Cell Reinfusion Autologous Hematopoietic Progenitor Cell Transplantation G-CSF G-CSF Mobilization Leukepheresis Busulfan Stem Cell Reinfusion Autologous Hematopoietic Progenitor Cell Transplantation Busulfan G-CSF Mobilization Leukepheresis Busulfan Stem Cell Reinfusion
- Primary Outcome Measures
Name Time Method 100-day Non-relapse Mortality 100 days post transplant 100-day non-relapse mortality is the number of participants who died before day 100 posttransplant from causes other than relapsed disease
- Secondary Outcome Measures
Name Time Method 1 Year Event-free Survival 1 year post transplant Number of participants alive and without disease relapse at 1 year posttransplant
Severe Regimen-related Toxicity up to 100 days post translant Number of participants with severe regimen-related toxicity within 2 years posttransplant. Severe regimen-related toxicity was defined as CTC (version 3)grade 4.
Successful Autologous Stem Cell Collection At time of stem cell collection Number of subjects who were able to collect at least 2 million CD34+ cells/kg
1 Year Overall Survival 1 year post transplant Number of participants alive at 1 year posttransplant
Trial Locations
- Locations (1)
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States