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Sponsored by: |
M.D. Anderson Cancer Center |
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Information provided by: | M.D. Anderson Cancer Center |
ClinicalTrials.gov Identifier: | NCT00469144 |
Primary Objectives:
To determine if busulfan (Bu) given in pharmacokinetically adjusted dose to yield a blood daily AUC of 6,000 microMol-min is superior to a fixed dose of 130 mg/m2 to prevent treatment failure (relapse or death from any cause) in patients with acute myelogenous leukemia and myelodysplastic syndrome.
This dose will be given intravenously over three hours once daily for four (4) days, each dose preceded by Fludarabine at a dose of 40 mg/m2, as preparation for bone marrow or peripheral blood progenitor cell transplantation.
Condition | Intervention | Phase |
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Myelodysplastic Syndrome Leukemia Acute Myeloid Leukemia |
Drug: Busulfan Drug: Fludarabine |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety/Efficacy Study |
Official Title: | A Randomized Study of Once Daily IV Busulfan With Fludarabine With Hemopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS) |
Estimated Enrollment: | 230 |
Study Start Date: | June 2005 |
Estimated Primary Completion Date: | June 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Fixed-Dose Busulfan + Fludarabine
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Drug: Busulfan
Arm 1 = 130 mg/m^2 IV Daily Over Three Hours x 4 Days; Arm 2 = 32 mg/m^2 IV Over 2 Hours Test Dose x 1 Day. Proceeding dosage level determined by pharmacokinetic studies to achieve a daily AUC of 6,000 microMol-min ± 10%.
Drug: Fludarabine
40 mg/m^2 IV Daily Over 1 Hour x 4 Days
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2: Experimental
Adjusted Dose Busulfan + Fludarabine
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Drug: Busulfan
Arm 1 = 130 mg/m^2 IV Daily Over Three Hours x 4 Days; Arm 2 = 32 mg/m^2 IV Over 2 Hours Test Dose x 1 Day. Proceeding dosage level determined by pharmacokinetic studies to achieve a daily AUC of 6,000 microMol-min ± 10%.
Drug: Fludarabine
40 mg/m^2 IV Daily Over 1 Hour x 4 Days
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Busulfan is a chemotherapy drug that kills cancer cells by binding to DNA, and is commonly used in stem cell transplantation. Fludarabine is an antimetabolite drug which has anti-leukemia and immunosuppressive effects.
Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have blood (about 3 tablespoons) drawn for routine tests. You will have a bone marrow biopsy, chest X-ray, sinus CT scan, and tests of heart and lung function. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. You will also have an electrocardiogram (ECG--a test to measure the electrical activity of the heart). Women who are able to have children must have a negative blood or urine pregnancy test before beginning treatment.
If you are eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 study groups. One group will receive a fixed dose of busulfan, while the other group will receive an adjusted dose of busulfan based on blood levels of the drug. Both groups will receive fludarabine treatment as well as a stem cell transplant.
Patients in the adjusted-dose group will first receive a low-level "test" dose of busulfan to check how their blood levels change over time; this information will be used to decide the next dose needed to reach the target blood level that matches your body size. Patients in the fixed-dose group will receive a fixed dose of busulfan without the test dose. If you are assigned to the fixed-dose group, this measurement will only affect your dose level if you have an unusually high or low drug level in your blood. Patients in both groups will have a total of about 20 teaspoons (less than 7 tablespoons) of blood drawn over time to check their busulfan blood levels following one or more of the busulfan treatments.
About 11 samples of blood will be drawn to check your blood levels of busulfan over time following the test dose and the first high-dose busulfan treatment; each sample is about 1 teaspoon of blood. A heparin lock will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for these blood level tests to be performed for technical or scheduling reasons, you will receive the standard fixed dose.
Both groups of patients receive fludarabine through a central venous catheter (CVC--a small tube inserted into one of your major veins, usually in the chest or shoulder blade) over 1 hour, once a day, for 4 days. After each dose of fludarabine, the high-dose Busulfan will be infused through the CVC over 3 hours. These drugs are given to try to kill malignant cells and suppress your immune system in order to reduce the risk of stem cell transplant rejection. If you are going to be receiving a transplant from an HLA-type-nonidentical or unrelated donor, you will also receive Thymoglobulin (ATG) over 4 hours on the 3 days prior to the transplant to further suppress your immune system.
After 2 days of rest, the allogeneic stem cells (bone marrow or peripheral blood stem cells) will then be given intravenously (IV--through a needle in your vein). You will receive the drug G-CSF (Neupogen) as an injection under the skin daily starting 1 week after the transplant until your blood cell levels return to normal.
Patients usually remain in the hospital for about 4 weeks after stem cell transplantation. After you are released from the hospital, you will continue as an outpatient in the hospital area to be monitored for infections and transplant-related complications for a minimum of 100 days after the transplant.
Patients who previously had leukemia involvement in the nervous system may need to receive spinal taps, with injection of cytosine arabinoside and hydrocortisone, several times over the year after transplantation to try to keep the leukemia from coming back.
You will undergo blood tests and bone marrow biopsies at 3, 6, and 12 months after the transplant, to check if the disease is in remission. Your health status will be followed along with their local physician to find out if the leukemia or myelodysplastic syndrome comes back, as well as to check the length of your survival.
This is an investigational study. All of the drugs used in this study are approved by the FDA for treatment of cancer. Up to 230 patients will take part in this study. All will be enrolled at M. D. Anderson.
Ages Eligible for Study: | up to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria: None
Contact: Richard E. Champlin, MD | 713-792-8750 |
United States, Texas | |
U.T.M.D. Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Principal Investigator: Richard E. Champlin, MD |
Principal Investigator: | Richard E. Champlin, MD | U.T.M.D. Anderson Cancer Center |
Responsible Party: | U.T.M.D. Anderson Cancer Center ( Richard E. Champlin, MD/Chair ) |
Study ID Numbers: | 2005-0366 |
Study First Received: | May 3, 2007 |
Last Updated: | January 5, 2009 |
ClinicalTrials.gov Identifier: | NCT00469144 History of Changes |
Health Authority: | United States: Institutional Review Board |
Stem Cell Transplantation Leukemia Busulfan |
Fludarabine MDS AML |
Antimetabolites Immunologic Factors Precancerous Conditions Hematologic Diseases Myelodysplastic Syndromes Leukemia, Myeloid Fludarabine monophosphate Leukemia, Myeloid, Acute Immunosuppressive Agents |
Leukemia Preleukemia Acute Myelocytic Leukemia Acute Myeloid Leukemia, Adult Busulfan Antineoplastic Agents, Alkylating Fludarabine Bone Marrow Diseases Alkylating Agents |
Antimetabolites Antimetabolites, Antineoplastic Precancerous Conditions Immunologic Factors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Physiological Effects of Drugs Leukemia, Myeloid, Acute Leukemia Preleukemia Pathologic Processes Syndrome Therapeutic Uses Alkylating Agents |
Disease Neoplasms by Histologic Type Hematologic Diseases Myelodysplastic Syndromes Leukemia, Myeloid Fludarabine monophosphate Immunosuppressive Agents Pharmacologic Actions Neoplasms Busulfan Myeloablative Agonists Fludarabine Antineoplastic Agents, Alkylating Bone Marrow Diseases |