TALL-104 and Gleevec in Chronic Myelogenous Leukemia Patients

Objectives:

• To determine the response rate and duration of response with combination of TALL-104 cells and imatinib mesylate (IM) therapy in patients with chronic myelogenous leukemia in chronic phase, that have not achieved, or have lost, adequate response to IM.
• To determine the toxicity of the combination of TALL-104 cells and IM therapy in this patient population.

Imatinib mesylate is designed to block the enzyme that is believed to be responsible for starting the type of leukemia you have. TALL-104 cells are cells of the immune system that have been obtained from a patient with leukemia and then processed in the laboratory to try to make them able to kill leukemia cells.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. Your complete medical history will be recorded. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, and temperature). Blood (about 2 tablespoons) will be drawn for routine tests and 1 additional tablespoon will be stored to be analyzed in case unexpected side effects occur after you receive your therapy. You will have a bone marrow aspirate/biopsy to check the status of the leukemia. To collect a bone marrow aspirate/biopsy, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow/bone is withdrawn through a large needle. Women who are able to have children must have a negative blood (about 1 teaspoon) pregnancy test.

If you are found to be eligible to take part in this study, you will continue receiving imatinib mesylate by mouth at the same schedule and dose you have been receiving before entering the study. You will receive TALL-104 cells through a needle in your vein over 1 hour on Days 1-4, and then again on Days 7, 10, 14, 17, and 21 of the cycle. The cycle will last 28 days.

Blood (about 1 tablespoon) will be drawn every week for the first 4 weeks, then every 2-4 weeks for 2 months, then every 4-6 weeks until 6 months, and then every 3-6 months for routine tests and to check for any effect on your organs.

You will have follow-up visits at 1 month, 3 months, 6 months, and at least annually for 2 years, and then at least every 5 years from then on for the rest of your life. Blood (about 1 teaspoon) will be drawn to check the status of the disease. An additional 1 tablespoon will also be collected and stored to be analyzed in case unexpected side effects occur after you receive your therapy. If you experience certain side effects, more blood may need to be drawn and more tests performed based on the side effects you may experience. You should inform the study staff if your address or telephone number changes.

This is an investigational study. TALL-104 is not FDA approved or commercially available. It has been authorized for use in research only. Imatinib mesylate is FDA approved and commercially available. Up to 20 patients will take part in this study. All will be enrolled at M. D. Anderson.

• Drug: Imatinib Mesylate (IM)
  IM Therapy of (100 mg or 400 mg) tablets by mouth, same dose each day.
  Other Name: Gleevec
• Drug: TALL-104 cells
  TALL-104 cells will be given intravenously over 1 hour at the dose of 109 cells daily for 4 days, on days 1 to 4 of the cycle, and then again on days 7, 10, 14, 17 and 21 of the cycle. One cycle is equal to 28 days. Patients will receive only one cycle of therapy with TALL-104 cells

Inclusion Criteria:

1. Patients with CML in chronic phase who have failed to achieve or have lost an adequate response to IM. For the purpose of this trial this will be defined as a lack of any cytogenetic response after 6 months of therapy or lack of major cytogenetic response after 12 months of therapy with IM. Patients that have lost their major or complete cytogenetic response will also be eligible. Patients who show a sustained increase in BCR-ABL/ABL ratio of >/= 1-log confirmed in at least two consecutive PCR analyses (at least one month apart from each other) will also be eligible.
2. *continued from above: Patients with stable molecular response defined as 2 consecutive PCR-positive results (no more than 1/2 log improvement) will also be eligible. Patients must be taking stable dose of IM for at least 3 months before study enrollment, and recovered from all toxicities related to IM, to grade 0-1.
3. Patients should be in complete or partial hematological remission, including WBC </=20 x 10(9)/L, and platelets </= 600 x 10(9)/L.
4. ECOG scale performance status of 2 or less.
5. Age greater than 18 years of age since disease is extremely rare in younger age groups.
6. Adequate liver (total bilirubin of less than 2 x and AST or ALT of less than 2 x upper limits of normal), and renal function (creatinine of less than 2 x upper limit of normal).
7. Signed informed consent form.
8. Negative pregnancy test in women of childbearing age.
9. Negative hepatitis B and C screening blood tests.

Exclusion Criteria:

1. Serious intercurrent medical illnesses or active infections requiring parenteral antibiotics that would interfere with the ability of the patient to carry out the treatment program.
2. Female patients who are pregnant or breast-feeding.
3. Patients taking steroids, or those anticipated to receive steroids during the trial therapy.
4. Prior bone marrow transplant.
5. Known positivity for HIV.