Clinical trial NCT00506857: Phase I/II Trial of Fludarabine Plus Busulfan and Allogeneic Progenitor Cell Support
Official title: Phase I/II Trial of Fludarabine in Combination With Intravenous Busulfan and Allogeneic Progenitor Cell Support for Patients With Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hematologic Malignancies
Keywords: Hematologic Malignancies
Blood And Marrow Transplantation
Leukemia
MDS
Lymphoma
Myeloma
Fludarabine
Fludara
Fludarabine Phosphate
Busulfan
Busulfex
Myleran
Progenitor Cell Transplantation
Granulocyte colony stimulating factor
G-CSF
Apheresis
Blood cell infusion
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2007-07-25
Enrollment: 82
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Objectives:

1. To determine the relative toxicities, engraftment potential, kinetics of engraftment, degree of chimerism and disease control achieved with the combination of fludarabine and busulfan at different dose levels and different dose schedules in patients undergoing allogeneic stem cell transplant (SCT).
2. Determine pharmacokinetics, and toxicity of intravenous busulfan given at equal total dose levels given four times daily, or once daily.
3. In vivo determination of fludarabine inhibitory effects on DNA repair.

Detailed description: 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 Cancer Center.

Eligibility criteria: Inclusion Criteria:

1. Less than physiologic 75 years of age.
2. Interferon resistant late chronic phase CML not eligible for a protocol of higher priority.
3. Accelerated/Blastic Phase CML.
4. Acute leukemia or Intermediate to High Risk MDS according to the IPPS.
5. Any Lymphoma or Myeloma beyond CR1 ineligible for a protocol of higher priority.
6. Patients must have an HLA compatible donor willing to donate either peripheral blood or bone marrow progenitor cells.
7. Both patients and donor must sign written informed consents.

Exclusion Criteria:

1. Uncontrolled infection
2. Bilirubin \>3.0
3. Creatinine \>2.5
4. Performance Status \>Zubrod 2

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 1 month
Secondary outcomes:
measure: Number of Participants With Graft Versus Host Disease (GVHD)
timeFrame: 5 years
Other outcomes:
Locations:
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: UT MD Anderson Cancer Center
name: Richard E. Champlin, MD, BS
role: PRINCIPAL_INVESTIGATOR
References: