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

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ClinicalTrials.gov Identifier: NCT00905034

Recruitment Status : Completed

First Posted : May 20, 2009

Results First Posted : June 29, 2015

Last Update Posted : June 29, 2015

Sponsor:

Collaborator:

Leadiant Biosciences, Inc.

Information provided by (Responsible Party):

M.D. Anderson Cancer Center

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Leukemia, Lymphocytic, Acute	Drug: Methotrexate Drug: Vincristine Drug: PEG-l-asparaginase Drug: Dexamethasone Drug: Rituximab	Phase 2

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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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	37 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase II Study of Methotrexate, Vincristine, Pegylated L-asparaginase and Dexamethasone (MOAD) in Acute Lymphoblastic Leukemia (ALL) Salvage
Study Start Date :	March 2009
Actual Primary Completion Date :	February 2015
Actual Study Completion Date :	February 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Dexamethasone Methotrexate Vincristine sulfate Dexamethasone sodium phosphate Asparaginase Dexamethasone acetate Pegaspargase

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Lymphosarcoma

U.S. FDA Resources

Arms and Interventions

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 Name: Rheumatrex Drug: Vincristine 1.4 mg/m^2 by vein (maximum dose 2 mg) on days 1, 8 and 15. Other Name: Oncovin® Drug: PEG-l-asparaginase 2500 International units/m^2 by vein on days 2 and 16 Other Names: Oncaspar® PEG asparaginase Pegaspargase Polyethylene Glycol Conjugated Lasparaginase-H Drug: Dexamethasone 40 mg by vein or by mouth daily days 1-4 and 15-18. Other Name: 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 Name: Rituxan®

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 Name: Rheumatrex

Drug: Vincristine

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

Other Name: Oncovin®

Drug: PEG-l-asparaginase

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

Other Names:

Oncaspar®
PEG asparaginase
Pegaspargase
Polyethylene Glycol Conjugated Lasparaginase-H

Drug: Dexamethasone

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

Other Name: 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 Name: Rituxan®

Outcome Measures

Primary Outcome Measures :

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.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	1 Year and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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;
Chronic myeloid leukemia in blast phase
Zubrod performance status </= 3;
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;
Age >/= to 1 year
Understand and voluntarily sign an informed consent form.
For pediatric patients (age >/= 1 year to </= 18 years), Lansky performance status >/=50
For pediatric patients (age >/= 1 year to </= 18 years), second or greater relapse

Exclusion Criteria:

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00905034

Locations

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

Sponsors and Collaborators

M.D. Anderson Cancer Center

Leadiant Biosciences, Inc.

Investigators

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

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

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Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00905034
Other Study ID Numbers:	2008-0267 NCI-2010-01147 ( Registry Identifier: NCI CTRP )
First Posted:	May 20, 2009 Key Record Dates
Results First Posted:	June 29, 2015
Last Update Posted:	June 29, 2015
Last Verified:	June 2015

Keywords provided by M.D. Anderson Cancer Center:


Acute lymphoblastic leukemia ALL Leukemia Methotrexate Vincristine PEG-l-asparaginase PEG asparaginase	Pegaspargase Oncaspar Polyethylene Glycol Conjugated Lasparaginase-H Dexamethasone Decadron Rituximab Rituxan

Additional relevant MeSH terms:

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Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Dexamethasone Rituximab Methotrexate Vincristine Asparaginase Pegaspargase	Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Antineoplastic Agents, Immunological Immunologic Factors Antirheumatic Agents Abortifacient Agents, Nonsteroidal

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