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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00506857
First received: July 23, 2007
Last updated: January 24, 2012
Last verified: January 2012
  Purpose

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.

Condition Intervention Phase
Hematologic Malignancies
Drug: Busulfan
Drug: Fludarabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    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:
  • Number of Participants With Graft Versus Host Disease (GVHD) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 82
Study Start Date: November 2003
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00506857

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

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00506857     History of Changes
Other Study ID Numbers: DM99-251
Study First Received: July 23, 2007
Results First Received: January 24, 2012
Last Updated: January 24, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Busulfan
Fludarabine phosphate
Fludarabine
Lenograstim
Vidarabine
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on August 01, 2014