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Busulfan (IV) and Fludarabine Followed by Post-allogeneic Transplantation Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies.


Phase 2
6 Months
75 Years
Open (Enrolling)
Both
Hematologic Diseases, Leukemia, Lymphoma, Myeloma

Thank you

Trial Information

Busulfan (IV) and Fludarabine Followed by Post-allogeneic Transplantation Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies.


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.


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
5. Calculated creatinine clearance of >50mL/min using the Cockroft-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 years of age who are unable to perform PFT, pulse oximetry >/= 92% on room air.

7. LVEF >/= 35%.

Exclusion Criteria:

1. HIV seropositivity

2. Uncontrolled infections.

3. Positive Beta 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence of Grade III to IV Acute GVHD and Non-relapse Mortality

Outcome Description:

Evaluations between first 25-35 days post transplant, and every 3 months up to a year, then followed up to 2 years.

Outcome Time Frame:

30 days post transplant

Safety Issue:

Yes

Principal Investigator

Amin Alousi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2008-0261

NCT ID:

NCT00800839

Start Date:

October 2008

Completion Date:

Related Keywords:

  • Hematologic Diseases
  • Leukemia
  • Lymphoma
  • Myeloma
  • Post-allogeneic transplantation
  • Graft-versus-Host Disease Prophylaxis
  • Graft-versus-Host Disease
  • GVHD
  • Hematologic malignancies
  • Leukemia
  • Lymphoma
  • Myeloma
  • Human Leukocyte Antigen
  • HLA
  • Busulfan
  • Cyclophosphamide
  • Fludarabine
  • Mesna
  • Cytoxan®
  • Neosar®
  • Busulfex
  • Myleran®
  • Fludarabine Phosphate
  • Graft vs Host Disease
  • Hematologic Diseases
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Hematologic Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030