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Sponsored by: |
University of California, San Francisco |
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Information provided by: | University of California, San Francisco |
ClinicalTrials.gov Identifier: | NCT00824525 |
The study hypothesis is that higher dose intravenous busulfan can be delivered safely to AML patients undergoing autologous transplantation. If this hypothesis is true the investigators plan to examine in a future study whether higher-dose busulfan can improve overall survival following autologous transplantation for AML.
Condition | Intervention | Phase |
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Acute Myelogenous Leukemia |
Drug: Etoposide, Cytarabine, Busulfan |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
Official Title: | A Phase I Study of Targeted, Dose-Escalated Intravenous Busulfan and Bolus Etoposide as Preparative Therapy for Patients With Acute Myeloid Leukemia Undergoing Autologous Stem Cell Transplantation |
Estimated Enrollment: | 48 |
Study Start Date: | April 2009 |
Estimated Study Completion Date: | April 2016 |
Estimated Primary Completion Date: | April 2015 (Final data collection date for primary outcome measure) |
Busulfan and etoposide have been used as preparative therapy for autoSCT (stem cell transplant) in adults with AML at UCSF for the past 10 years. Over this period and together with collaborative transplant centers, over 200 patients have received this treatment. By intent-to-treat analysis, and with median follow-up of 7.0 years, the 5-year DFS is 55%. The current protocol will utilize the combination of IV Busulfan (BU) and etoposide. The busulfan dose will be escalated amongst 3 targeted dose levels. All targeted dose levels represent higher busulfan dosing than standard myeloablative dosing, with the lowest dose being approximately 14% higher than standard. Busulfan levels will be monitored after the first, fourth and twelfth doses. Dose adjustments will be made "in real time" based on AUC levels determined from the first and fourth doses. This strategy of busulfan monitoring and dose adjustment has improved the therapeutic widow of BU in previous clinical trials.
The current protocol will utilize the combination of intravenous busulfan and etoposide. The busulfan dose will be escalated amongst 3 targeted dose levels (area under the curve (AUC) levels at time 6 hours of 1250 uMol*min, 1400 uMol*min and 1550 uMol*min). All targeted dose levels represent higher busulfan dosing than standard myeloablative dosing with the lowest dose (1250 uMol*min) being approximately 14% higher than standard. In the absence of dose-limiting toxicity, cohorts of 4-6 patients will be treated at each dose level and 10 additional patients will be treated at the maximum tolerated dose (MTD) to confirm safety. The busulfan dosing will begin at 1 mg/kg based on historical plasma levels obtained from patients receiving BU at a starting dose of 0.8 mg/kg at UCSF Medical Center.
The highest dose level proposed for this study will exceed the reported toxic level for busulfan in the alloSCT setting. Patients will be followed closely for toxicity and strict stopping rules have been included. Eligibility criteria will exclude patients with prior history of hepatotoxicity or viral hepatitis. Potential hepatotoxic agents will not be allowed just prior to and during the busulfan dosing period. In addition, patients who experience hepatotoxicity during pre-transplant mobilization therapy may be excluded from receiving dose-escalated busulfan therapy. Every attempt will be made to prevent or avoid hepatotoxicity.
Ages Eligible for Study: | 18 Years to 69 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Natalie Jeha, M.A. | 415.476.4126 | njeha@medicine.ucsf.edu |
United States, California | |
University of California San Francisco | |
San Francisco, California, United States, 94143 |
Responsible Party: | University of California, San Francisco ( Thomas Martin, M.D. ) |
Study ID Numbers: | 082516 |
Study First Received: | January 14, 2009 |
Last Updated: | January 15, 2009 |
ClinicalTrials.gov Identifier: | NCT00824525 History of Changes |
Health Authority: | United States: Institutional Review Board |
AML busulfan etoposide Preparative therapy for Autologous Stem Cell Transplantation |
Antimetabolites Immunologic Factors Leukemia, Myeloid Leukemia, Myeloid, Acute Antiviral Agents Etoposide phosphate Immunosuppressive Agents Leukemia |
Acute Myelocytic Leukemia Acute Myeloid Leukemia, Adult Busulfan Antineoplastic Agents, Alkylating Antineoplastic Agents, Phytogenic Etoposide Alkylating Agents Cytarabine |
Antimetabolites Anti-Infective Agents Antimetabolites, Antineoplastic Neoplasms by Histologic Type Molecular Mechanisms of Pharmacological Action Immunologic Factors Antineoplastic Agents Physiological Effects of Drugs Leukemia, Myeloid Leukemia, Myeloid, Acute Antiviral Agents Etoposide phosphate |
Immunosuppressive Agents Pharmacologic Actions Leukemia Neoplasms Therapeutic Uses Busulfan Myeloablative Agonists Antineoplastic Agents, Alkylating Antineoplastic Agents, Phytogenic Alkylating Agents Etoposide Cytarabine |