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A Randomized Study of Once Daily IV Busulfan With Fludarabine With Hemopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Phase 3
65 Years
Open (Enrolling)
Myelodysplastic Syndrome, Leukemia, Acute Myeloid Leukemia

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Trial Information

A Randomized Study of Once Daily IV Busulfan With Fludarabine With Hemopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS)

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.

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 MD Anderson.

Inclusion Criteria:

1. Acute myeloid leukemia past first remission, in first or subsequent relapse, in first
remission (cytogenetics other than t(8;21, inv 16, t(15;17)) or induction failures.
Only myeloid leukemia but not biphenotypic leukemia is allowed on this study.

2. Myelodysplastic syndromes with intermediate or high risk International Prognostic
Scoring System score

3. Patient has not been administered any other systemic chemotherapeutic drug (including
Mylotarg) within 21 days prior to trial enrollment (BMT Day -7 or day -9 for the
test-dose arm of the study). Hydroxyurea is permitted if indicated to control
induction refractory disease, and IT chemotherapy is allowed if indicated as
maintenance treatment for previously diagnosed leptomeningeal disease, that has been
in remission for at least 3 months prior to enrollment on this study).

4. No active infection. Protocol PI will be final arbiter if there is uncertainty
regarding whether a previous infection is resolved.

5. age <=65

6. Patients must have a matched related or unrelated donor willing to donate. A donor
who is HLA identical or mismatched in 1 locus on Class I [HLA, A or B], or
molecularly mismatched in 1 locus on Class II [HLA, DR or DQ] is also acceptable.

7. ZUBROD performance status <2

8. Life expectancy is not severely limited by concomitant illness and expected to be >12

9. Left ventricular ejection fraction >45% No uncontrolled arrhythmias or symptomatic
cardiac disease.

10. No symptomatic pulmonary disease. FEV1, FVC and DLCO >/= 50% of expected corrected
for hemoglobin. In patients pediatric BMT routine

11. Serum creatinine
12. SGPT laboratory standard normal limits or considered not clinically significant. No
evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology,
discuss with Study Chairman and consider liver biopsy.

13. No effusion or ascites >1L prior to drainage.

14. HIV-negative.

15. Female patient is not pregnant (negative B-HCG pregnancy test in all women of
child-bearing-potential in accordance with departmental routine).

16. Patient or patient's legal representative, parent(s) or guardian able to sign
informed consent.

17. No prior autologous stem cell transplants.

Exclusion Criteria: None

Type of Study:


Study Design:

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

Outcome Measure:

Time to failure (TTF)

Outcome Time Frame:

From transplant at Day 0 to Day 100 following transplant then quarterly thereafer (3, 6, 12 months)

Safety Issue:


Principal Investigator

Richard E. Champlin, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

June 2005

Completion Date:

Related Keywords:

  • Myelodysplastic Syndrome
  • Leukemia
  • Acute Myeloid Leukemia
  • Stem Cell Transplantation
  • Leukemia
  • Busulfan
  • Fludarabine
  • MDS
  • AML
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



UT MD Anderson Cancer Center Houston, Texas  77030