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

June 9, 2015 updated by: M.D. Anderson Cancer Center

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MOAD
Chemotherapy regimen of methotrexate, rituximab, vincristine, pegylated L-asparaginase and dexamethasone (MOAD).
Drug: Methotrexate
200 mg/m^2 by vein on days 1 and 15.
Other Names:
  • Rheumatrex
Drug: Vincristine
1.4 mg/m^2 by vein (maximum dose 2 mg) on days 1, 8 and 15.
Other Names:
  • Oncovin®
Drug: PEG-l-asparaginase
2500 International units/m^2 by vein on days 2 and 16
Other Names:
  • Pegaspargase
  • PEG asparaginase
  • Oncaspar®
  • Polyethylene Glycol Conjugated Lasparaginase-H
Drug: Dexamethasone
40 mg by vein or by mouth daily days 1-4 and 15-18.
Other Names:
  • Decadron®
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.
Other Names:
  • Rituxan®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response (CR) Rate
Time Frame: 6 cycles (cycle = 28 days)
Rate calculated as number of participants with CR. Complete Remission (CR) defined as Normalization of peripheral blood and bone marrow with 5% or less blasts in a normocellular or hypercellular marrow with a granulocyte count of 1 x 10^9/L or above and platelet count of 100 x 10^9/L or above. Complete resolution of all sites of extramedullary disease is required for CR.
6 cycles (cycle = 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

Leadiant Biosciences, Inc.

Investigators

  • Principal Investigator: Gautam Borthakur, M.D., M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

May 18, 2009

First Submitted That Met QC Criteria

May 18, 2009

First Posted (Estimate)

May 20, 2009

Study Record Updates

Last Update Posted (Estimate)

June 29, 2015

Last Update Submitted That Met QC Criteria

June 9, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2008-0267
  • NCI-2010-01147 (Registry Identifier: NCI CTRP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe