High-Dose Gleevec Alone or in Combination With Peg-Intron and GM-CSF in Early Phase Chronic Myelogenous Leukemia (CML)

Study Overview
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Brief Summary
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The goal of this clinical research study is to learn if giving PEG-Alpha Interferon (PEG-Intron) and Sargramostim (GM-CSF) to patients receiving treatment with high dose Gleevec (imatinib mesylate) is more effective in treating CML in chronic phase than therapy with imatinib mesylate alone.

Detailed Description
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Imatinib mesylate is a drug that blocks a protein that is responsible for the development of CML. PEG-Intron is a natural substance made by the cells of the immune system and helps to control CML. GM-CSF is a hormone that helps to stimulate the production of white blood cells. During the study you will take 400 mg of imatinib mesylate by mouth 2 times a day (800 mg a day total). Imatinib mesylate should be taken each morning and evening with a large glass of water. You may be given a pill diary to write down when (day and time) you take the drug. You may also write in the diary any side effects you may experience. You may bring the diary, any unused tablets, and empty bottles of imatinib mesylate with you to every visit to the study doctor. Any unused supplies must be returned at the end of the study. After completing 6 months of imatinib mesylate therapy, you will be randomly assigned (as in the toss of a coin) to one of two groups. Patients in the first group will be given PEG-Intron and GM-CSF in addition to imatinib mesylate therapy. Patients in the other group will continue taking only imatinib mesylate. If you are assigned to the group that will receive PEG-Intron and GM-CSF, you will continue taking imatinib mesylate. In addition, PEG-Intron will be given as an injection under the skin once a week. Sargramostim will be given as an injection under the skin 3 times a week. You and/or your family members can be taught to give these injections. Every 1-2 weeks during the first 4 weeks of the study, you will have around 2 teaspoons of blood drawn for routine blood tests and to measure the amount of imatinib in your blood. The blood tests will then be repeated every 6 to 8 weeks (or more often if your doctor feels it is necessary) for as long as you are on the study. A bone marrow sample will also be taken every 3 months for the first year and then every 4 to 6 months for as long as you are on the study to check on the status of the disease . You will be asked to visit the doctor for a physical exam and to have vital signs measured. These visits will be scheduled at least every 3 months while you are on the study. The visits may be scheduled more often depending on the status of the disease. Update: February 2012: Blood test are recommended 2 times per year. Your doctor will discuss with you how often you should have blood tests. Bone marrow will be done if your doctor thinks it is needed to check the disease. You must return to M.D. Anderson at least once every year. You may not need a bone marrow test every visit, but you will have blood drawn to measure the amount of disease you have. Treatment in both groups may be continued for up to 7-10 years, or as long as the doctor feels is necessary to control the leukemia. If the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you. This is an investigational study. All of the drugs used in this study are FDA approved and commercially available. However, their use in this study is investigational. A total of 98 patients will take part in this study. All will be enrolled at MD Anderson.

Official Title
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Randomized Trial of Therapy of Early Phase Chronic Myelogenous Leukemia With High-Dose Imatinib Mesylate (Gleevec) Alone or in Combination With Peg-Alpha Interferon (PEG-Intron) and Sargramostim (GM-CSF)

Conditions
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Leukemia, Myeloid, Chronic

Intervention / Treatment
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* Drug: Gleevec
* Drug: Peg-alpha interferon (Peg-Intron)
* Drug: Sargramostim (GM-CSF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Ph-positive CML in early chronic phase CML who have received no or minimal prior therapy, (<1 month of prior IFN-alpha (with or without ara-C) and/or Gleevec). Eastern Cooperative Oncology Group (ECOG) performance of 0-2. Adequate end organ function, defined as the following: total bilirubin < 1.5 x upper limit of normal (ULN), serum glutamate pyruvate transaminase (SGPT) < 2.5 x ULN, creatinine < 1.5 x ULN Signed informed consent. Exclusion Criteria: New York Heart Association (NYHA) cardiac class 3-4 heart disease. Psychiatric disability (psychosis) Pregnant or lactating females Late chronic phase, accelerated or blastic phase

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gleevec<br>Gleevec 400 mg orally twice daily. | Drug: Gleevec<br>* 400 mg orally twice daily.<br>* Other names: STI-571;Drug: Peg-alpha interferon (Peg-Intron)<br>* PEG-IFN 0.5 mcg/kg each week subcutaneously.<br>* Other names: Interferon Alfa-2b (PEG conjugate);|
| Experimental: Gleevec + Peg-Intron + GM-CSF<br>Gleevec 400 mg orally twice daily. Peg-Intron 0.5 mcg/kg each week subcutaneously. GM-CSF 125 mcg/m^2 three times per week subcutaneously. | Drug: Gleevec<br>* 400 mg orally twice daily.<br>* Other names: STI-571;Drug: Peg-alpha interferon (Peg-Intron)<br>* PEG-IFN 0.5 mcg/kg each week subcutaneously.<br>* Other names: Interferon Alfa-2b (PEG conjugate);Drug: Sargramostim (GM-CSF)<br>* 125 mcg/m^2 three times per week subcutaneously.<br>* Other names: Granulocyte-Macrophage Colony Stimulating Factor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Pathological Complete Response Negativity or Cytogenetic Response | Duration measured in time from first response to disease progression; Cytogenetic (or FISH), and PCR quantification every 3-4 months as indicated in year one then FISH every 1-3 years and PCR every year | Molecular response at 12 Months and Polymerase Chain Reaction (PCR) testing once a year (+/- 3 months) | 
| Number of Participants with Complete Hematologic Remission (CHR) Classification of Complete Cytogenetic Response | Complete Hematologic Remission (CHR) - normalization >4 weeks of bone marrow (less than 5% blasts) & peripheral blood with white blood count (WBC)<10x10^9/L & no peripheral blasts, promyelocytes or myelocytes, disappearance of all signs & symptoms of disease. Partial Hematologic Response (PHR) = CHR except persistence of immature cells (myelocytes, metamyelocytes), or splenomegaly <50% of pretreatment, or thrombocytosis >450x10^9/L but <50% of pretreatment. Complete hematologic remission further classified according to suppression of Philadelphia chromosome (Ph) by cytogenetics or fluorescence in situ hybridization (FISH): a) No cytogenetic response - Ph positive 100% of pretreatment value; b) Minor cytogenetic response - Ph positive 35-90% of pretreatment value; c) Partial cytogenetic response - Ph positive 1-34% of pretreatment value; d) Complete cytogenetic response - Ph positive 0%. | Molecular response at 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Myelogenous Leukemia, CML, Early Chronic Phase Chronic Myelogenous Leukemia, Imatinib Mesylate, Gleevec, Peg-Alpha Interferon, Peg-Intron, Sargramostim, GM-CSF