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Sponsors and Collaborators: |
University of North Carolina ESP Pharma |
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Information provided by: | The University of North Carolina, Chapel Hill |
ClinicalTrials.gov Identifier: | NCT00618306 |
The primary purpose of this study is to identify the maximum tolerated dose of continuous infusion IV busulfan in conjunction with fludarabine and alemtuzamab plus tacrolimus for GVHD prophylaxis. We will also identify the dose limiting toxicities of this regimen and assess the capacity of test dosing of busulfan and targeted busulfan dosing to result in the desired AUC exposure of patients receiving full-dose busulfan. We will also estimate the overall and disease-free survival of patients enrolled on this study.
Condition | Intervention | Phase |
---|---|---|
Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndromes Agnogenic Myeloid Metaplasia |
Drug: Busulfan |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
Official Title: | Allogeneic Hematopoietic Cell Transplantation for Patients With Hematologic Disorders Who Are Undergoing Dose-Adjusted Treatment With a Maximally Intensive Busulfex-Based Therapeutic Regimen |
Estimated Enrollment: | 30 |
Study Start Date: | October 2005 |
Estimated Study Completion Date: | September 2009 |
Estimated Primary Completion Date: | September 2008 (Final data collection date for primary outcome measure) |
Allogeneic hematopoietic cell transplantation (allo-HCT) from a matched related (MRD) or matched unrelated (MUD) donor can effect a cure or prolongation of overall and disease-free survival in a significant proportion of patients with hematologic malignancies. Unlike autologous stem cell transplantation, this approach ensures a graft that is free of tumor-cell contamination, and enables the provision of adoptive immunotherapy mediated by donor-derived T-lymphocytes and possibly natural killer cells (graft-versus-malignancy effect, GVM).
The majority of allogeneic transplants over the years have utilized either oral busulfan or total body irradiation (TBI) as the ablative component of the conditioning regimen in conjunction usually with cyclophosphamide or etoposide for immunosuppression or additional anti-tumor efficacy. While these approaches have been curative in anywhere from 20% to 70% of patients, depending on the disease status and diagnosis, such approaches have also been associated with treatment related mortality rates (TRM) of 20% to 50%, again varying with patient age, quality of donor match, cytomegalovirus (CMV) infection risk, etc. In trials where regimens using TBI have been compared to busulfan based regimens, the overall outcomes have generally been similar, although there is a suggestion that TBI may be slightly more effective in reducing relapse risk for acute leukemia patients but has greater cumulative toxicities. Toxicities between the two approaches are different, with busulfan resulting in more hepatic toxicity and TBI generating more acute pulmonary, GI, lung, ocular toxicity, and second malignancies as well as inducing growth retardation in children.
In this study we will escalate the dose of continuous infusion busulfan based on AUC data obtained from pharmacokinetics following a single dose of this drug prior to initiating the ablative regimen. It is hypothesized that this approach will allow for identification of a new maximum tolerated dose (MTD) with different dose-limiting toxicities than observed with intermittent infusion schedules. These higher doses may allow for greater efficacy and less toxicity than conventional administration schedules.
Ages Eligible for Study: | 18 Years to 55 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Julia S Whitley, BS | 919-966-7313 | whitleyj@med.unc.edu |
Contact: Thomas C Shea, MD | 919-966-7746 | sheat@med.unc.edu |
United States, North Carolina | |
University of North Carolina Hospitals | Recruiting |
Chapel Hill, North Carolina, United States, 27599 | |
Sub-Investigator: Don A Gabriel, MD, PhD | |
Principal Investigator: Celeste Lindley, PharmD | |
Sub-Investigator: Jonathan Serody, MD, PhD | |
Sub-Investigator: Terrance Comeau, MD | |
Sub-Investigator: Robert Irons, PA-C | |
Sub-Investigator: Christine Walko, PharmD |
Principal Investigator: | Thomas C Shea, MD | UNC Chapel Hill |
Responsible Party: | UNC Lineberger Comprehensive Cancer Center ( Thomas Shea, MD/Principal Investigator ) |
Study ID Numbers: | LCCC 0510 |
Study First Received: | February 7, 2008 |
Last Updated: | February 19, 2008 |
ClinicalTrials.gov Identifier: | NCT00618306 History of Changes |
Health Authority: | United States: Institutional Review Board |
Allogeneic transplant Busulfan |
Precancerous Conditions Immunologic Factors Blood Protein Disorders Paraproteinemias Hemostatic Disorders Leukemia Preleukemia Hemorrhagic Disorders Metaplasia Alkylating Agents Lymphoma Myelofibrosis Immunoproliferative Disorders Hematologic Diseases |
Blood Coagulation Disorders Myelodysplastic Syndromes Myeloproliferative Disorders Vascular Diseases Immunosuppressive Agents Multiple Myeloma Myeloid Metaplasia Lymphatic Diseases Busulfan Antineoplastic Agents, Alkylating Bone Marrow Diseases Lymphoproliferative Disorders Neoplasms, Plasma Cell |
Molecular Mechanisms of Pharmacological Action Immunologic Factors Precancerous Conditions Antineoplastic Agents Blood Protein Disorders Physiological Effects of Drugs Paraproteinemias Hemostatic Disorders Leukemia Preleukemia Hemorrhagic Disorders Pathologic Processes Therapeutic Uses Syndrome Metaplasia |
Cardiovascular Diseases Alkylating Agents Lymphoma Myelofibrosis Disease Neoplasms by Histologic Type Immunoproliferative Disorders Immune System Diseases Hematologic Diseases Myelodysplastic Syndromes Myeloproliferative Disorders Vascular Diseases Immunosuppressive Agents Pharmacologic Actions Multiple Myeloma |