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

NCT ID: NCT00905034

Last Updated: 2015-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2015-02-28

Brief Summary

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 chronic myeloid leukemia (CML).

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 cluster of differentiation antigen 20 (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.

Conditions

Leukemia, Lymphocytic, Acute

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MOAD

Chemotherapy regimen of methotrexate, rituximab, vincristine, pegylated L-asparaginase and dexamethasone (MOAD).

Group Type: EXPERIMENTAL

Methotrexate

Intervention Type: DRUG

200 mg/m\^2 by vein on days 1 and 15.

Vincristine

Intervention Type: DRUG

1.4 mg/m\^2 by vein (maximum dose 2 mg) on days 1, 8 and 15.

PEG-l-asparaginase

Intervention Type: DRUG

2500 International units/m\^2 by vein on days 2 and 16

Dexamethasone

Intervention Type: DRUG

40 mg by vein or by mouth daily days 1-4 and 15-18.

Rituximab

Intervention Type: DRUG

Rituximab 375 mg/m\^2 by vein on days 1 and 15 (first 4 cycles) for patients CD20 positive or positive by immunostain.

Interventions

Methotrexate

200 mg/m\^2 by vein on days 1 and 15.

Intervention Type: DRUG

Vincristine

1.4 mg/m\^2 by vein (maximum dose 2 mg) on days 1, 8 and 15.

Intervention Type: DRUG

PEG-l-asparaginase

2500 International units/m\^2 by vein on days 2 and 16

Intervention Type: DRUG

Dexamethasone

40 mg by vein or by mouth daily days 1-4 and 15-18.

Intervention Type: DRUG

Rituximab

Rituximab 375 mg/m\^2 by vein on days 1 and 15 (first 4 cycles) for patients CD20 positive or positive by immunostain.

Intervention Type: DRUG

Other Intervention Names

Rheumatrex; Oncovin®; Oncaspar®; PEG asparaginase; Pegaspargase; Polyethylene Glycol Conjugated Lasparaginase-H; Decadron®; Rituxan®

Eligibility 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 </= 3;

4. Adequate liver function (bilirubin </= 3.0mg/dl, unless considered due to tumor),and renal function (creatinine </= 3.0 mg/dl unless considered due to tumor;

5. Age >/= to 1 year

6. Understand and voluntarily sign an informed consent form.

7. For pediatric patients (age >/= 1 year to </= 18 years), Lansky performance status >/=50

8. For pediatric patients (age >/= 1 year to </= 18 years), second or greater relapse

Exclusion Criteria

1. Pregnant patients

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

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Leadiant Biosciences, Inc.

INDUSTRY

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gautam Borthakur, M.D.

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

NCI-2010-01147

Identifier Type: REGISTRY

Identifier Source: secondary_id

2008-0267

Identifier Type: -

Identifier Source: org_study_id