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Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Nelarabine in Patients With Relapsed/Refractory Lymphoid Malignancies

2014-08-27 03:14:57 | BioPortfolio

Summary

The goal of the clinical research study is to find the highest tolerable dose of nelarabine when given as a continuous infusion to patients with a lymphoid malignancy that has not responded to, or has come back after treatment with chemotherapy. The safety of this drug will also be studied.

Primary Objectives:

- To determine the toxicity profile and maximum tolerated dose (MTD) of a 5-day continuous infusion schedule of nelarabine.

Secondary Objectives:

- To assess the pharmacokinetics of infusional nelarabine.

- To assess leukemic cell ara-GTP levels during infusional nelarabine.

- To describe the response rate among different histologies (exploratory aim).

Description

The Study Drug:

Nelarabine is designed to interfere with DNA (the genetic material of cells) and stop the growth of rapidly dividing cells, such as cancer cells.

Screening Tests:

Signing this consent form does not mean that you will be able to take part in this study. You will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:

- Your complete medical history will be recorded.

- You will have a physical exam, including measurement of your vital signs (blood pressure, temperature, and breathing).

- You will be asked about any drugs you are taking and about any chemotherapy treatments you have had.

- You will be asked how well you are able to perform the normal activities of daily living (performance status).

- Blood (about 2 tablespoons) will be drawn for routine tests.

- You will have a chest x-ray to check the status of the disease.

- You will have a bone marrow biopsy and aspiration to check the status of the disease. To collect a bone marrow aspirate/biopsy, an area of the hip bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.

- You will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart).

- If you have non-Hodgkin's lymphoma (NHL), you will have a computed tomography (CT) scan of the chest, abdomen, and pelvis to check the status of the disease.

- If you have leftover tumor tissue available, the tumor tissue will be used to confirm the disease.

- If you do not have leftover tissue available, you will have a biopsy or fine-needle aspiration (FNA) of a lymph node or disease-involved tissue to confirm the disease.

- Women who are able to have children must have a negative blood or urine pregnancy test. If a blood pregnancy test is performed, blood from the routine sample listed above will be used. No additional needle sticks will be required.

The study doctor will discuss the screening test results with you. If the screening tests show that you are not eligible to take part in the study, you will not be enrolled. Other treatment options will be discussed with you.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of nelarabine based on when you joined this study. Up to 4 dose levels of nelarabine will be tested. Three (3) to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of nelarabine is found.

Study Drug Administration:

You will receive nelarabine as a non-stop infusion through a needle or catheter in your vein on Days 1-5 of each 21-day cycle. You will remain in the hospital for this infusion.

You may receive ondansetron or a similar drug by vein over about 30 minutes before you receive nelarabine. This is given to help prevent nausea. You will also take ondansetron or a similar drug by mouth every 12 hours for the next 7 days as needed. If you are still having nausea, you will be given additional drugs.

If you are not allergic, you may receive allopurinol by mouth on Days 1-10 of Cycles 1. Allopurinol is given to help reduce the risk of too much uric acid in the blood. If the level of uric acid in the blood is too high, you may receive additional drugs.

You may also be given drugs to help reduce the risk of infection.

Study Visits:

On Day 1 of Cycle 1 only, blood (about 2 teaspoons each time) will be drawn for pharmacokinetic (PK) and pharmacodynamic (PD) testing 1 hour before, then again 2, 4, 6, and between 10-18 hours after the study drug infusion. PK testing measures the amount of study drug in the body at different time points. PD testing measures how the level of study drug in your body may affect the disease

On Days 2, 3, 4, and 5 of Cycle 1 only, blood (about 2 teaspoons) will be drawn for PK and PD testing.

On Day 1 of each cycle:

- You will have a physical exam, including measurement of your vital signs.

- You will be asked about any drugs you are taking and about any transfusions you may have had.

- You will be asked about any side effects you may have had.

- Your performance status will be recorded.

- Measurements of your lymph nodes, spleen, and liver will be taken.

- Blood (about 2 teaspoons) will be drawn to test the levels of antibodies and T-cells (a type of white blood cell) in your blood.

One (1) time each week, or more often if the study doctor thinks it is needed:

- You will have a physical exam, including measurement of your vital signs.

- You will be asked about any side effects you may have had.

- Your performance status will be recorded.

- Blood (about 4 teaspoons) will be drawn for routine tests.

After every 3 cycles:

- You will have a physical exam, including measurement of your vital signs.

- You will be asked about any drugs you are taking and about any transfusions you may have had.

- You will be asked about any side effects you may have had.

- Your performance status will be recorded.

- Measurements of your lymph nodes, spleen, and liver will be taken.

- Blood (about 4 teaspoons) will be drawn for routine tests.

- You will have a neurological exam (tests to check the functioning of your nerves, including tests of your balance and reflexes).

- Blood (about 2 teaspoons) will be drawn to check the number of T-cells in your blood.

- You will have a bone marrow aspirate/biopsy to check the status of the disease.

- If you have NHL, you will have CT scan of the chest, abdomen, and pelvis to check the status of the disease.

Length of Participation:

You may continue to receive nelarabine for as long as the study doctor thinks it is in your best interest. You will no longer be able to receive the study drug if the disease gets worse or intolerable side effects occur.

Additional Information:

- Most standard drugs can be taken while on this study.

- Drugs known as "growth factors" cannot be taken during Cycle 1 unless the study doctor thinks it is needed for the treatment of a severe fever due to low white blood cell counts.

- Your doctor will tell you about any other drugs that cannot be taken while on study.

This is an investigational study. Nelarabine, given as an injection, is FDA approved for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia or T lymphoblastic lymphoma. The use of nelarabine as a continuous infusion is investigational.

Up to 15 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study Design

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

Conditions

Leukemia

Intervention

Nelarabine

Location

UT MD Anderson Cancer Center
Houston
Texas
United States
77030

Status

Recruiting

Source

M.D. Anderson Cancer Center

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:14:57-0400

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A replication-defective strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) capable of transforming lymphoid cells and producing a rapidly progressing lymphoid leukemia after superinfection with FRIEND MURINE LEUKEMIA VIRUS; MOLONEY MURINE LEUKEMIA VIRUS; or RAUSCHER VIRUS.

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A chronic leukemia characterized by a large number of circulating prolymphocytes. It can arise spontaneously or as a consequence of transformation of CHRONIC LYMPHOCYTIC LEUKEMIA.

A lymphoid leukemia characterized by a profound LYMPHOCYTOSIS with or without LYMPHADENOPATHY, hepatosplenomegaly, frequently rapid progression, and short survival. It was formerly called T-cell chronic lymphocytic leukemia.

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