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Busulfan, Fludarabine, Clofarabine With Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia

Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute Myeloid Leukemia; Myelodysplastic Syndrome; Chronic Myeloid Leukemia

Intervention: Clofarabine (Drug); Busulfan (Drug); Fludarabine (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Richard E. Champlin, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Summary

The goal of this clinical research study is to find the best dose of clofarabine and fludarabine that can be given with busulfan followed by an allogeneic blood stem cell transplant. Researchers will study whether this combination can help to control the disease, and look at the safety of this combination. Researchers also want to find out if combining busulfan with clofarabine alone or combining busulfan with both fludarabine and clofarabine will improve the treatment, compared with the previous standard method using busulfan and fludarabine alone.

Clinical Details

Official title: Busulfan-Fludarabine-Clofarabine With Allogeneic Stem Cell Transplantation for Advanced Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, and Advanced, Gleevec Refractory Chronic Myeloid Leukemia. A Randomized Phase II Study.

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Optimal Dose Level

Secondary outcome: Treatment Related Mortality

Detailed description: Busulfan is a chemotherapy drug that kills cancer cells by binding to DNA (the genetic material of cells). Clofarabine is designed to interfere with the growth and development of cancer cells. Fludarabine is designed to interfere with DNA repair enzymes so that the leukemic cells cannot repair damaged DNA. This may increase the likelihood of the cell dying. These drugs are being given to try to kill cancerous cells and weaken your immune system in order to lower the risk of stem cell transplant rejection. If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 4 study groups. Three (3) of the groups will receive busulfan, fludarabine, and clofarabine at different dose levels. The 4th group will only receive busulfan and clofarabine. As the study continues, participants will be assigned using a method called adaptive randomization. This method works by increasing the chances of being assigned to the group that has had the best results in the study so far. You will know which group you have been assigned to. Participants will receive busulfan, fludarabine, and/or clofarabine once a day for 4 doses. You will first receive an additional low-level "test" dose of busulfan given by vein to check how your blood levels change over time. This information will be used to decide the next dose needed to reach a target blood level of busulfan. You will have a total of about 6 and 1/2 tablespoons of blood drawn over time to check your busulfan blood levels following one or more of the busulfan treatments. Up to 11 samples of blood will be drawn to check your blood levels of busulfan during the next 11 hours following the test dose and the first high-dose busulfan treatment. Each sample will require about 1 teaspoon of blood. A heparin lock line will be placed in a 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 (unchanging) dose of busulfan. Clofarabine and fludarabine (if applicable) will be given through a central venous catheter (CVC) over 1 hour, once a day, for 4 days. Busulfan will also be given through the CVC over 3 hours. If you are going to be receiving a transplant from an HLA-nonidentical or unrelated donor, you will also receive thymoglobulin (ATG) over 4 hours on the 3 days before the transplant to further weaken your immune system to reduce the risk of rejecting of the transplant. After the transplant, you will receive tacrolimus, methotrexate, or other immunosuppressive (lowering the immune system) drugs in the standard manner to lower the risk of graft-vs-host disease (GVHD), a reaction of the donor's immune cells against the recipient's body. The allogeneic stem cells (bone marrow or peripheral blood stem cells) will also be given through the CVC. You will receive the drug G-CSF (filgrastim) as an injection under the skin once a day, starting 1 week after the transplant, until your blood cell levels return to normal. Patients usually stay in the hospital for about 4 weeks after stem cell transplantation. After you are released from the hospital, you will continue to be monitored as an outpatient for infections and transplant-related complications for at least 100 days after the transplant. You will have blood tests (about 4 tablespoons of blood) and bone marrow aspirations performed at 1, 3, 6, and 12 months after the transplant, to check if the disease is in remission (has not come back). Your health status will be followed with the help of your local doctor to find out if the leukemia or MDS 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. Busulfan has been approved for use in stem cell transplantation. The use of these drugs together with stem cell transplant is experimental. Up to 70 patients will take part in this study. All will be enrolled at the M. D. Anderson Cancer Center.

Eligibility

Minimum age: N/A. Maximum age: 60 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Diagnosis or 1) Acute myeloid leukemia past first remission, in first or subsequent relapse, or induction failures, 2) Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score (IPSS scores) (16), and having failed previous chemotherapy, or 3) Chronic Myeloid Leukemia, Philadelphia-chromosome positive and having failed / being resistant to therapy based on Gleevec or other tyrosine kinase inhibitors. 2. Patient has not been administered intensive systemic chemotherapeutic drugs within 21

days prior to trial enrollment (bone marrow transplant (BMT) Day - 9). Gleevec,

alternative tyrosine kinase inhibitors, other nonmyelosuppressive agents, low dose cytarabine, hydroxyurea is permitted if indicated to control the leukemia. All tyrosine inhibitor- or other non-myelosuppressive agents have to be terminated at least one week prior to admission for this treatment. 3. No uncontrolled infection. Protocol principal investigator (PI) will be final arbiter if there is uncertainty regarding whether a previous infection is resolved on appropriate antibiotics therapy. 4. age /=45% No uncontrolled arrhythmias or symptomatic cardiac disease. 9. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) >/= 50% of expected corrected for hemoglobin. In patients 1L prior to drainage. 2. HIV-positive. 3. Hepatitis C or HBsAg positive 4. Prior stem cell transplant after a myeloablative conditioning program (such as busulfan-based using a total dose of >/= 12 mg/kg given by mouth or >/= 10 mg/kg IV, or a total-body irradiation-based program. 5. Active or prior Central Nervous System (CNS) leukemia 6. Biphenotypic acute leukemia.

Locations and Contacts

UT MD Anderson Cancer Center, Houston, Texas 77030, United States
Additional Information

UT MD Anderson Cancer Website

Starting date: September 2006
Last updated: April 1, 2013

Page last updated: August 23, 2015

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