Methotrexate, Vincristine, Pegylated L-Asparaginase and Dexamethasone (MOAD) in Acute Lymphoblastic Leukemia (ALL) Salvage

Condition(s) targeted: Leukemia, Lymphocytic, Acute

Intervention: Methotrexate (Drug); Vincristine (Drug); PEG-l-asparaginase (Drug); Dexamethasone (Drug); Rituximab (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Gautam Borthakur, M.D., Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Overall contact:
Gautam Borthakur, M.D., Phone: 713/563-1586, Email: gborthak@mdanderson.org

This goal of this clinical research study is to learn if the combination of methotrexate, pegylated-L-asparaginase, vincristine, and dexamethasone (also rituximab in some patients) can help to control ALL that has not responded to previous treatment or has come back after a response or CML.

Official title: Phase II Study of Methotrexate, Vincristine, Pegylated L-asparaginase and Dexamethasone (MOAD) in Acute Lymphoblastic Leukemia (ALL) Salvage

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

Primary outcome: Complete Response (CR) Rate Defined as Number of Participants Who Achieve a Complete Response

Detailed description: The Study Drugs:

Methotrexate is designed to disrupt cells from making and repairing DNA (the genetic material of cells) and "copying" themselves.

Vincristine 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.

Pegylated-L-asparaginase is designed to get rid of an important building block of proteins in leukemia cells.

Dexamethasone is a steroid that causes the leukemia cells to breakdown.

Rituximab is designed to attach to lymphoma cells, which may cause them to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive methotrexate through a needle in your vein on Days 1 and 15 (+/- 2 days) over 2 hours. You will receive vincristine by vein on Days 1, 8 and 15 (+/- 2 days) over 30 minutes. You will receive pegylated-L-asparaginase by vein on Days 2 and 16 (+/- 2 days) over about 2 hours. You will receive dexamethasone by vein over about 30 minutes or by mouth on Days 1-4 and 15-18 (+/- 2 days). If leukemia cells have a protein called CD20, you will also receive rituximab by vein on Days 1 and 15 of Cycles 1-4 (+/- 2 days) over about 2-8 hours.

Each cycle will be at least 28 days.

If you have Philadelphia positive ALL, you may continue to receive a tyrosine kinase inhibitor (TKI). Examples of TKIs include Imatinib, Dasatinib, and Nilotinib. If you are not taking a TKI, you may begin taking a TKI. Your doctor will describe treatment with TKIs with you in more detail.

Once your blood counts improve and your leukemia is under control your doctor may decide to continue on treatment every 4-6 weeks. If your leukemia is not under control after the first cycle, your doctor may decide to start the next cycle without your blood counts improving.

Study Visits:

During Cycle 1, blood (about 2 teaspoons) will be drawn at least 1 time each week for routine tests. If the doctor thinks it is necessary, you may be asked to have additional blood drawn.

Between Days 14-28 of Cycle 1, you will have a bone marrow aspirate to check the status of the disease. This test may be delayed or repeated if your doctor does not think you are in remission.

Since pegylated-L-asparaginase can cause problems with blood clotting and inflammation of the pancreas, on Days 2 and 16 of All cycles, blood (about 2 teaspoons) will be drawn to check how well your blood clots and to check the health of your pancreas.

During Cycles 2- 6, blood (about 2 teaspoons) will be drawn for routine tests at least 2 times each month.

If the doctor thinks it is necessary, you may have a bone marrow aspirate to check the status of the disease.

Length of Study:

You may receive the study drugs for up to 6 cycles. You will be taken off study early if the disease gets worse, you experience intolerable side effects, or your doctor thinks that it is no longer in your best interest to receive the study drug(s).

This is an investigational study. Methotrexate, pegylated-L-asparaginase, and vincristine are all FDA approved for use in ALL. Dexamethasone is FDA approved as a steroid and steroids are traditionally an important part of treatment of leukemia. Rituximab is FDA approved for the treatment of non-Hodgkin's lymphoma. The combination of all these drugs is investigational.

Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.

Minimum age: 1 Year. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Previously treated ALL (including Burkitt's lymphoma) or lymphoblastic lymphoma in relapse or primary refractory; without viable stem cell transplant option. Patients with previously treated Philadelphia chromosome positive ALL will be also eligible;

2. Chronic myeloid leukemia in blast phase

3. Zubrod performance status 4. Adequate liver function (bilirubin 5. Age >/= to 1 year

6. Understand and voluntarily sign an informed consent form.

7. For pediatric patients (age >/= 1 year to /=50

8. For pediatric patients (age >/= 1 year to Exclusion Criteria:

1. Pregnant patients

2. Prior history of allergic reaction, serious pancreatitis, hemorrhagic or thrombotic event with PEG-l-asparaginase or its components.

Gautam Borthakur, M.D., Phone: 713/563-1586, Email: gborthak@mdanderson.org

UT MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Gautam Borthakur, M.D., Phone: 713-563-1586, Email: gborthak@mdanderson.org
Gautam Borthakur, M.D., Principal Investigator

M.D. Anderson's Website

Starting date: May 2009
Last updated: October 30, 2012