NCT00506857 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2012-02-28

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Maximum Tolerated Dose (MTD)

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outcome · POSTED

Number of Participants With Graft Versus Host Disease (GVHD)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
maximum Age: 75 Years
sex: ALL
std Ages: CHILD
ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: Busulfan
Drug: Fludarabine
label
Busulfan + Fludarabine
type
EXPERIMENTAL

interventions

arm Group Labels
Busulfan + Fludarabine
description
Starting Dose 0.8 mg/kg by vein every 6 hours x 12 doses.
name
Busulfan
other Names
Busulfex
Myleran
type
DRUG
arm Group Labels
Busulfan + Fludarabine
description
30 mg/m\^2 by vein daily x 4 days.
name
Fludarabine
other Names
Fludarabine phosphate
Fludara
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 82
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Maximum Tolerated Dose (MTD)
time Frame
1 month

secondary Outcomes

description
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.
measure
Number of Participants With Graft Versus Host Disease (GVHD)
time Frame
5 years

Full study description

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.

Source references