Busulfan and Fludarabine Followed by Post-transplant Cyclophosphamide

NCT ID: NCT00800839

Last Updated: 2016-09-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-09-30

Brief Summary

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The goal of this clinical research study is to learn if cyclophosphamide given after busulfan and fludarabine can help to prevent graft versus host disease (GVHD - a condition in which transplanted tissue attacks the body into which it is transplanted) in patients receiving a stem cell transplant. The safety of this drug combination will also be studied.

Detailed Description

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The Study Drugs:

Busulfan is designed to bind to DNA (the genetic material of cells), which may cause cancer cells to die.

Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying.

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die. It is also designed to suppress the immune system and help prevent GVHD.

Study Drug Administration and Transplant:

If you are an inpatient, on Day -8 (8 days before the date of transplant), you will receive a low-level test dose of busulfan through a needle in your vein over 1 hour.

If you are an outpatient, on Day -30 through Day -8, you will receive a low-level test dose of busulfan through a needle in your vein over 1 hour each day.

You will be given an anti-seizure drug to help prevent seizures each time you receive busulfan. Your doctor will explain how the drug will be given and the drug's risks. Seizures are a rare but serious side effect of busulfan.

On Days -8, -6, and -4, blood (about 1 teaspoon each time) will then be drawn a total of 11 times for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the body at different time points. This PK testing will be done to find the dose of busulfan needed for your body size on the other days that you receive busulfan.

On Day -6 through Day -3, you will receive your body-specific dose of busulfan by vein over 3 hours each day. If you cannot have the blood level tests performed for any reason, you will receive the standard busulfan dose. You will receive fludarabine through a needle in your vein over 1 hour on each of these days before you receive busulfan.

On Day 0, you will receive the donor bone marrow or blood stem cells by vein over about 1 hour.

On Day +3 and Day +4, you will receive cyclophosphamide by vein over 3 hours.

On Days +3 thru +5 just before the first dose of cyclophosphamide and then every 4 hours, you will receive mesna by vein over 30 minutes for a total of 10 doses. Mesna is a drug that protects bladder cells from damage by chemotherapy drugs. It is used to decrease the risk of bleeding in the bladder.

Once a day starting on Day +7, you will receive filgrastim (G-CSF -- a drug that helps with the growth of white blood cells) through a needle under your skin until your blood cell levels reach "recovered" levels for 3 days in a row.

Study Visits:

Every day you are in the hospital and at each outpatient visit, you will have a physical exam to check for symptoms of GVHD.

Blood (about 3 teaspoons) will be drawn at least 2 times a week for the first 100 days after the transplant for routine tests.

About 1 month after your transplant, then once every 3 months up to a year, the following tests and procedures will be performed:

* Blood (about 5 tablespoons) will be drawn for routine tests and to check for CMV. Blood draws may be repeated more often, if you doctor thinks it is needed.
* Urine will be collected for routine tests.
* You will have a bone marrow aspirate and biopsy to check the status of the disease.

At Months 1, 2, 3, 6, and 12 after your transplant, blood (about 4 tablespoons) will be drawn to check the status of your immune system.

Tests and procedures may be repeated more often during the study, if your doctor thinks it is needed.

Length of Study:

You will be on study in the hospital for about 4 weeks. You will be taken off study if the disease gets worse or if the study doctor thinks it is in your best interest.

Long-Term Follow-Up:

After the first 24 months, you will receive either a phone call or a letter from the study doctor or your regular doctor 1 time each year to check the status of the disease. If you are contacted by mail, you will be given a self-addressed stamped envelope with which you can return your responses to the doctor.

This is an investigational study. Busulfan is FDA approved and commercially available for the treatment of chronic myelogenous leukemia (CML). Fludarabine is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). Cyclophosphamide is FDA approved and commercially available for the treatment of lymphoma. The use of these drugs together for the possible prevention of GVHD is investigational.

Up to 40 participants will take part in this study. All will be enrolled at M. D. Anderson.

Conditions

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Hematologic Diseases Leukemia Lymphoma Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Busulfan + Fludarabine + Cyclophosphamide

Busulfan starting dose of 32 mg/m\^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m\^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.

Group Type EXPERIMENTAL

Busulfan

Intervention Type DRUG

Starting dose of 32 mg/m\^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3.

Fludarabine

Intervention Type DRUG

Dose of 40 mg/m\^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan.

Cyclophosphamide

Intervention Type DRUG

Dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.

Interventions

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Busulfan

Starting dose of 32 mg/m\^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3.

Intervention Type DRUG

Fludarabine

Dose of 40 mg/m\^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan.

Intervention Type DRUG

Cyclophosphamide

Dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.

Intervention Type DRUG

Other Intervention Names

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Bulsulfex™ Myleran® Fludarabine Phosphate Fludara Cytoxan® Neosar®

Eligibility Criteria

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Inclusion Criteria

1. Patients with high risk hematological malignancies, including those with induction failure and after treated or untreated relapse.
2. HLA-identical sibling or matched unrelated donor transplants not eligible for protocols of higher priority.
3. Age 6 months to 75 years.
4. Bilirubin \</= 1.5 mg/dl, serum glutamate pyruvate transaminase (SGPT) \</= 200 IU/ml (unless Gilbert's syndrome).
5. Calculated creatinine clearance of \>50mL/min using the Cockcroft-Gault equation for adult patients 18 to 70 years old, and the Schwartz equation for pediatric patients 6 months to 17 years old.
6. Diffusing capacity for carbon monoxide (DLCO) \>45% predicted corrected for hemoglobin (as reported by the Pulmonary Function Laboratory at MDACC). For most children \</= 6 years of age who are unable to perform pulmonary function test (PFT), pulse oximetry \>/= 92% on room air.
7. left ventricular ejection fraction (LVEF) \>/= 35%.

Exclusion Criteria

1. HIV seropositivity
2. Uncontrolled infections.
3. Positive Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
4. Inability to sign consent
Minimum Eligible Age

6 Months

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Amin Alousi, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

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NCI-2012-01660

Identifier Type: REGISTRY

Identifier Source: secondary_id

2008-0261

Identifier Type: -

Identifier Source: org_study_id

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