Phase I/II Trial of Fludarabine Plus Busulfan and Allogeneic Progenitor Cell Support

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00506857
Recruitment Status : Completed
First Posted : July 25, 2007
Results First Posted : February 28, 2012
Last Update Posted : February 28, 2012
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:


  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.

Condition or disease Intervention/treatment Phase
Hematologic Malignancies Drug: Busulfan Drug: Fludarabine Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Fludarabine in Combination With Intravenous Busulfan and Allogeneic Progenitor Cell Support for Patients With Hematologic Malignancies
Study Start Date : November 2003
Actual Primary Completion Date : August 2011
Actual Study Completion Date : August 2011

Arm Intervention/treatment
Experimental: Busulfan + Fludarabine
Busulfan starting 0.8 mg/kg by vein (IV) every 6 hours for 12 doses; Fludarabine 30 mg/m^2 IV daily for 4 days.
Drug: Busulfan
Starting Dose 0.8 mg/kg by vein every 6 hours x 12 doses.
Other Names:
  • Busulfex
  • Myleran
Drug: Fludarabine
30 mg/m^2 by vein daily x 4 days.
Other Names:
  • Fludarabine phosphate
  • Fludara

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 1 month ]
    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.

Secondary Outcome Measures :
  1. Number of Participants With Graft Versus Host Disease (GVHD) [ Time Frame: 5 years ]
    Tacrolimus and Methotrexate used for acute graft versus host disease (aGVHD) prophylaxis, clinical grading AGVHD criteria (Days 1-100): Grade 1: + to ++ skin rash; no gut involvement; no decrease in clinical performance status; Grade 2: + to +++ skin rash; + gut involvement and/or + liver involvement; mild decrease in performance status; Grade 3: ++ to +++ skin rash; ++ to +++ gut involvement and/or ++ to ++++ liver involvement; marked decrease in performance status; Grade 4: Similar to Grade 3 with ++ to ++++ organ involvement and extreme decrease in performance status.

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Ages Eligible for Study:   up to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00506857

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Richard E. Champlin, MD, BS UT MD Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00506857     History of Changes
Other Study ID Numbers: DM99-251
First Posted: July 25, 2007    Key Record Dates
Results First Posted: February 28, 2012
Last Update Posted: February 28, 2012
Last Verified: January 2012

Keywords provided by M.D. Anderson Cancer Center:
Hematologic Malignancies
Blood And Marrow Transplantation
Fludarabine Phosphate
Progenitor Cell Transplantation
Granulocyte colony stimulating factor
Blood cell infusion

Additional relevant MeSH terms:
Fludarabine phosphate
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists