Phase I/II Trial of Fludarabine in Combination With Intravenous Busulfan and Allogeneic Progenitor Cell Support for Patients With Hematologic Malignancies
Treatment: Participants will have blood tests and bone marrow tests as well as tests to
check lung, heart, kidney, and liver functions. Participants will receive busulfan by vein
for 2 to 4 days depending on their age and medical condition. All participants will receive
fludarabine which will be given over 4 days. Participants undergoing unmatched or matched
unrelated donors will receive ATG over 4 days to help with the engraftment of the donor
progenitor cells. All drugs are given through the vein daily.
The donor blood cells will be taken from the donor through a process known as apheresis.
This will occur after the donor has received 2 days of granulocyte colony stimulating factor
(G-CSF) to increase her/his white cell count. The G-CSF will also increase the number of
very immature (stem cells) that are to be collected. Apheresis is similar to a platelet
donation, but white cells and stem cells are collected instead. About 3 to 5 apheresis
procedures will be needed to get enough cells for infusion. If apheresis is not used, donor
bone marrow will be taken under general anesthesia.
After the participants receives the donor stem cells, the stem cells divide and reconstitute
bone marrow function, blood function, and immunity. The donor stem cells are given after
the chemotherapy to shorten the period of low blood counts. They are also given at this
time to achieve an antileukemic effect whereby the donor immune cells will recognize the
participant's leukemia as "foreign" and prevent its recurrence. A small amount of donor
cells will be kept for infusion on a future date (usually 3 and 6 months post transplant) to
try to prevent the disease from coming back.
During the 4 to 8 weeks following blood cell infusion, participants will need frequent blood
tests to monitor their counts and blood chemistries. Participants will need frequent blood
transfusion and may have to be admitted to the hospital to receive antibiotics if they
develop fever. Bone marrow will be examined frequently beginning four weeks after treatment
to check response. Participants that achieve normal bone marrow and blood counts will be
evaluated to determine the most appropriate form of future therapy. Participants who fail
to respond to treatment will be offered other therapies.
This is an investigational study. All through all drugs are commercially available. Up to
140 participants will take part in this study. All will be enrolled at UT MD Anderson
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
Continual reassessment method (four times a day) used to determine an MTD, with a target toxicity probability of 20%, where "toxicity" is defined as grade 3 or 4 conventional toxicity [National Cancer Institute Common Toxicity Criteria (NCI-CTC)]. Participant evaluation in a cohort with each modality is 30 days.
Richard E. Champlin, MD, BS
UT MD Anderson Cancer Center
United States: Institutional Review Board
|UT MD Anderson Cancer Center||Houston, Texas 77030|