- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00363467
Busulfan Monotherapy as Conditioning for Autologous Hematopoietic Progenitor Cell Transplantation
A Pilot Study of Intravenous, Targeted-Dose Busulfan Monotherapy as Conditioning for Autologous Hematopoietic Progenitor Cell Transplantation in High-Risk AML
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Pre- Transplantation Phase -
- 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.
- 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.
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.
Supportive care
- Antibiotic prophylaxis- according to hospital/institutional guidelines, and at the discretion of the treating physician.
- Growth factor support
- Transfusion support
- Prophylaxis for busulfan-induced seizures
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
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Florida
-
Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center & Research Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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)
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]
- AML arising from antecedent hematologic disorder (e.g. MDS)
- Secondary AML (t-AML)
Exclusion Criteria:
- 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 Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Autologous Hematopoietic Progenitor Cell Transplantation
G-CSF Mobilization Leukepheresis Busulfan Stem Cell Reinfusion
|
Mobilization Option 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. Mobilization Option 2: If patients have recovered hematologically from consolidation chemotherapy, they may receive G-CSF at 10 mcg/kg twice daily subcutaneously.
Other Names:
leukapheresis
Busulfan IV daily x 4 days (transplantation days -5,-4,-3,-2).
The day -5 and -4 dose will be 130mg/m2
Other Names:
autologous stem cell transplant
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
100-day Non-relapse Mortality
Time Frame: 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
|
100 days post transplant
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Successful Autologous Stem Cell Collection
Time Frame: At time of stem cell collection
|
Number of subjects who were able to collect at least 2 million CD34+ cells/kg
|
At time of stem cell collection
|
Severe Regimen-related Toxicity
Time Frame: 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.
|
up to 100 days post translant
|
1 Year Event-free Survival
Time Frame: 1 year post transplant
|
Number of participants alive and without disease relapse at 1 year posttransplant
|
1 year post transplant
|
1 Year Overall Survival
Time Frame: 1 year post transplant
|
Number of participants alive at 1 year posttransplant
|
1 year post transplant
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Jeffrey E Lancet, MD, H. Lee Moffitt Cancer Center and Research Institute
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Busulfan
Other Study ID Numbers
- MCC-14604
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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