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Busulfan, Cyclophosphamide, Imatinib Mesylate and Autologous Stem Cell Transplantation in Patients With Chronic Myelogenous Leukemia


Phase 2
N/A
70 Years
Not Enrolling
Both
Chronic Myelogenous Leukemia

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Trial Information

Busulfan, Cyclophosphamide, Imatinib Mesylate and Autologous Stem Cell Transplantation in Patients With Chronic Myelogenous Leukemia


Busulfan and cyclophosphamide are chemotherapy drugs which were designed to kill leukemia
cells. An autologous bone marrow transplant is given after treatment with busulfan and
cyclophosphamide to help in the recovery of blood and immune cells after this treatment.
Imatinib mesylate is a drug which helps to stop the growth of leukemia cells. It is given
after the transplant to help kill any remaining leukemia cells.

Before treatment, you will have a complete physical exam. You will have approximately 4
tablespoons of blood drawn for tests to check on the status of the disease, to check organ
functions, and to check for infectious diseases (hepatitis, HIV, etc.). You will have a
sample of bone marrow collected. To collect a bone marrow sample, an area of the hip or
chest bone is numbed with anaesthetic and a small amount of bone marrow is withdrawn through
a large needle. All of these tests are being done to make sure you are eligible for this
treatment. If you are found to have a "blast crisis," you will not be eligible to continue
on this study.

If you are eligible or if it has not already been done recently, you will be taken to the
operating room and have around 4-6 cups of bone marrow collected. The procedure will be
performed under general anesthesia. The procedure is similar to the bone marrow collection
at the start of the study, however, more bone marrow will be collected. The bone marrow
that is collected will be frozen and stored to be given back to you after high dose
chemotherapy. Before the procedure, you will be asked to donate blood (if possible). This
blood will be given back to you after the procedure to replace the bone marrow that was
collected. You may also need a blood transfusion from another donor.

For patients who cannot undergo the procedure of bone marrow harvesting or if not enough
bone marrow was collected during the bone marrow harvesting procedure, stem cells may be
collected from the blood. Normally, there are very few stem cells in the blood. Most of
them are in the bone marrow. To help move or "mobilize" the cells needed from your bone
marrow to your blood, you will be given injections under the skin once a day of a drug
called G-CSF. The injections may given by a nurse in the hospital, in the outpatient
setting, or you may learn how to give the injection yourself. Blood samples (1 tablespoon)
will be drawn every day to see if there are enough stem cells in your blood. After 4-6 days
of treatment with G-CSF, you will undergo a procedure called leukapheresis. This procedure
is similar to donating blood to a blood bank. Blood is collected and run through a machine
that processes the blood and separates the cells needed for transplantation, giving the rest
back to you. The separated cells are frozen and stored to give back you after high dose
chemotherapy. You may need up to 3 leukapheresis procedures to collect enough cells.

Patients who had adequate amounts of their bone marrow or blood stem cells harvested in the
past will not need additional harvesting of stem cells.

At a future time when the leukemia shows signs of growth, you will have a catheter (small,
flexible tube) inserted under the collar bone into a large vein in the chest. This catheter
will allow the chemotherapy drugs, fluids, and other medications to be given more easily.
You will have approximately 4 tablespoons of blood drawn for tests to check on the status of
the disease, to check organ functions, and to check for infectious diseases (hepatitis, HIV,
etc.). You will have a sample of bone marrow collected. You will also have heart (cardiac
ejection fraction) and lung function tests.

You will be admitted to the hospital to receive high dose chemotherapy. You will be given
busulfan by continuous injection (using the catheter) for 4 days, then you will be given
cyclophosphamide by a continuous injection (using the catheter) for 2 days. The amount of
busulfan you receive may be adjusted to help decrease the risk of developing side effects.
You may also receive antibiotics, fluids, and other medications if your doctor feels it is
necessary.

After high dose chemotherapy, you will be given your stored bone marrow or blood stem cells
back ("transplant"). They will be given back to you through the catheter to help restore
blood production and immunity after high dose chemotherapy. To help speed up the recovery
of white blood cells, you will also be given G-CSF by injection under the skin daily until
the white blood count has recovered (usually 2 to 3 weeks). You may also receive
antibiotics, fluids, and other medications if your doctor feels it is necessary. Blood
tests are repeated several times per week until blood counts are fully recovered and any
side effects of the high dose therapy have resolved.

After your blood counts have recovered, you will begin treatment with imatinib mesylate by
mouth for up to 1 year. You may also receive medications to help prevent infections for
around 6 months after the transplant. These medications are usually pills to help prevent
pneumonia and viral infections. While you are taking imatinib mesylate you will have blood
collected (1- 4 tablespoons) for routine tests . The frequency of these blood collections
will depend on your medical condition.

Around 1, 3, 6, 12, 18, and 24 months after transplant, you will have check-up visits. At
these visits, you will have blood collected (1- 4 tablespoons) for routine blood tests and
have a sample of bone marrow collected for tests. This bone marrow collection will be
repeated 3, 4, and 5 years after the transplant procedure.

This is an investigational study. All of the drugs used in this study are FDA approved and
are commercially available. Up to 50 participants will take part in this study. All will
be enrolled at M. D. Anderson.


Inclusion Criteria:



1. Criteria for hematopoietic stem cell collection and cryopreservation: a- Patients
with Philadelphia chromosome positive CML < age 70 who achieve a cytogenetic
remission (no Ph+ cells on bone marrow cytogenetics, at least twenty metaphases
counted) are eligible for hematopoietic stem cell collection and cryopreservation. b-
Patients must have a Zubrod PS <2. c.Creatinine < 1.8 mg/dl d.Serum bilirubin < 1.5
mg/dl e. SGPT < 3 x normal values f. Patients with an HLA identical sibling are
eligible if they refuse allogeneic transplantation.

2. Patients are eligible for high dose therapy and autologous transplantation if they
meet the following criteria (numbered 2-13): - Cytogenetic relapse characterized by >
10% Ph+ metaphases (by FISH analysis or > 2 of 20 Ph+ metaphases on 2 consecutive
cytogenetic studies at least 1 month apart).

3. Cytogenetic relapse (as above) with hematologic remission or chronic phase disease,
or

4. Accelerated phase or second or subsequent chronic phase.

5. Availability of stored autologous hematopoietic stem cells collected when the patient
was in cytogenetic complete remission (0 of >= 20 metaphases positive for Ph+
cells).A minimum of 0.5 x 10 6 CD34 positive cells/kg or 1 x 10 8 total nucleated
cells/Kg must be available.

6. Age < 70 years.

7. Zubrod PS <=2.

8. Creatinine < 1.8 mg/dL.

9. Cardiac ejection fraction > 40%.

10. DLCO > 50% of the predicted value.

11. Serum bilirubin < 1.5 mg/dL.

12. SGPT < 3 x normal values.

13. Patients with an HLA identical sibling are eligible if they refuse allogeneic
transplantation.

Exclusion Criteria:

1. Uncontrolled life-threatening infections or comorbid condition that could impair
tolerance to the regimen.

2. HIV positivity.

3. Pregnant or lactating women.

4. Blast crisis (>30% blasts in blood or marrow)

5. Hepatitis B or C positivity.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of participants with CML alive in cytogenetic remission at one year following treatment

Outcome Description:

Cytogenetic complete remission confirmed via bone marrow examination for morphology, cytogenetics or Fluorescence in situ hybridization (FISH).

Outcome Time Frame:

Baseline to 1 Year post treatment, up to 18 months

Safety Issue:

No

Principal Investigator

Marcos de Lima, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

ID02-672

NCT ID:

NCT01003054

Start Date:

March 2005

Completion Date:

October 2009

Related Keywords:

  • Chronic Myelogenous Leukemia
  • Leukemia
  • CML
  • Busulfan
  • Busulfex
  • Myleran
  • Cyclophosphamide
  • Cytoxan
  • Neosar
  • Imatinib Mesylate
  • Gleevec
  • Autologous Stem Cell Transplantation
  • Stem Cell Transplant
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030