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Imatinib Mesylate

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Tyrosine

Imatinib Mesylate 300 mg orally twice daily starting 7 days before surgery.

Imatinib Mesylate 300 mg orally twice daily starting 5 days before surgery.

Imatinib Mesylate 300 mg orally twice daily starting 3 days before surgery.

Imatinib Mesylate (Gleevec)

Jonathan Trent, MD, PhD

Primary objectives

1. To determine whether induction of apoptosis or inhibition of angiogenesis are involved in the antitumor activity of (Gleevec, Formerly STI-571) in patients with gastrointestinal stromal tumors (GIST) as assessed by Positron Emission Tomography (PET) scanning.
2. To determine whether dynamic computed tomography (CT), PET scan, molecular and histopathologic responses in GIST tumors from patients treated with Gleevec predict Disease-Free Survival (DFS) time.

Secondary objectives

1. To determine the disease free survival of patients with resectable or partially resectable gastrointestinal stromal tumors treated with Gleevec preoperatively and continued for 2 years after resection of disease.
2. To assess the safety and tolerability of Gleevec given to patients with GI stromal tumors 3, 5, or 7 days preoperatively and continued postoperatively.

Imatinib mesylate is a drug that may help to kill gastrointestinal stromal tumor cells.

Around 3 weeks before your scheduled surgery, you will have a PET scan, a CT scan and two to three tablespoons of blood will be collected. These are imaging tests and are being done to check on the status of the disease. These tests will be repeated the day before your scheduled surgery. If your doctor feels it is necessary, you will have a chest x-ray and 2 to 3 tablespoons of blood will be collected for routine tests. Women who are able to have children must have a negative blood pregnancy test.

Before treatment, you will also have a biopsy procedure of the tumor performed. This biopsy is being done to study the effect of imatinib mesylate on the tumor cells. The tissue that is collected during the biopsy procedure will be compared to the tumor that is taken out at the time of surgery.

You will be randomly assigned (as in the toss of a coin) to one of three groups. One group will begin taking imatinib mesylate two times a day by mouth starting 7 days before surgery. The second group will start taking imatinib mesylate 5 days before surgery. Participants in the third group will begin taking imatinib mesylate 3 days before surgery. After your surgery, the removed tumor will be studied and compared to the tissue collected before surgery to see what effect (if any) imatinib mesylate had on the tumor. All patients will then continue imatinib mesylate for 2 years after surgery.

You will take imatinib mesylate two times a day for 2 years.

If you develop any side effects to the study drug, treatment may be temporarily stopped or the dose of the drug changed until the symptoms are gone. 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.

You will be seen by a physician regularly after surgery. Two to three tablespoons of blood will be collected once a month for routine tests, and a you will have a CT scan done every 3 months. These tests will help us determine if your cancer has come back.

THIS IS AN INVESTIGATIONAL STUDY. Imatinib mesylate is FDA approved and is commercially available. Up to 48 participants will take part in this study. All will be enrolled at M. D. Anderson.

Preoperative and Postoperative Imatinib Mesylate Study in Patients With c-Kit Positive GIST

A Prospective, Randomized, Phase II Study of Preoperative Plus Postoperative Imatinib Mesylate (Gleevec, Formerly STI-571) in Patients With Primary, Recurrent, or Metastatic Resectable, Kit-Expressing, Gastrointestinal Stromal Tumor (GIST)

Effect of drug imatinib mesylate on gastrointestinal stromal tumors (GIST) by disease-free survival (DFS) time, measured from the start of Gleevec therapy, among the three arms to disease progression or 2 years postoperative therapy, measured in months.

Novartis

M.D. Anderson Cancer Center

Jonathan Trent, MD, PhD/Assistant Professor

Blood and Lymph Conditions

Immune System Diseases

Syndrome

Leukemia

Mastocytosis

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Polycythemia Vera

Polycythemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Hypereosinophilic Syndrome

Leukemia, Myelomonocytic, Acute

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myelodysplastic-Myeloproliferative Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Mast Cell Activation Disorders

Eosinophilia

Leukocyte Disorders

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Mitogens

Imatinib mesylate 400 mg orally daily, and in HES patients start with imatinib mesylate 100 mg orally daily.

Imatinib mesylate 400 mg orally daily, and in HES patients start with imatinib mesylate 100 mg orally daily

Jorge Cortes, MD

The goal of this clinical research study is to see if Gleevec, known as imatinib mesylate (STI571), can improve the disease condition in patients with hypereosinophilic syndrome, polycythemia vera, atypical CML or CMML with PDGF-R fusion genes, or mastocytosis.

Imatinib mesylate is a chemical compound that blocks a protein that is responsible for a certain form of leukemia. However, imatinib mesylate also blocks other important proteins that may be responsible for other blood diseases such as myeloproliferative disorders.

Patients in this study will take 4 tablets of imatinib mesylate by mouth every day. Patients with HES will take 1 tablet daily to begin, and may go up to 4 tablets daily depending on response. Imatinib mesylate should be taken each morning at breakfast with a large glass of water. Bottles containing the tablets will be given to the patient every month. Unused supplies must be returned at the end of the study. Patients taking oral hydroxyurea to control their blood counts, can continue it during the first month of imatinib mesylate treatment, but must stop taking it from then on.

After completing 2 months of therapy, response to imatinib mesylate will be evaluated. If the response is good, treatment with imatinib mesylate alone will be continued. If the response is not good, the dose of imatinib mesylate will be increased to 8 tablets daily (4 in the morning and 4 in the evening) or may be decreased to 3 tablets daily. This will be based on how the drug is tolerated. Treatment may be continued for up to one year, or as long as it is judged best to control the leukemia.

Patients will be asked to visit their doctor for a physical exam and vital signs. The frequency of doctor visits will vary depending on physical condition.

Blood tests (about 2 teaspoons) will be done once each year. The blood samples will be used for routine lab tests. A bone marrow sample will also be taken to check and measure cells related to the disease after 3 - 4 months, then every 3-6 months in the first year. If the initial bone marrow sample does not show disease, repeated bone marrows will not be done.

This is an investigational study. Imatinib mesylate has been approved in CML for patients whose disease has not responded to interferon. However, this is an investigational study in patients with myeloproliferative diseases. The FDA has authorized the use of imatinib mesylate in research. A total of 145 patients will take part in this study. All will be enrolled at MD Anderson.

Therapy of HES, PV, Atypical Chronic Myelocytic Leukemia (CML) or Chronic Myelomonocytic Leukemia (CMML), and Mastocytosis With Imatinib Mesylate

Therapy of Hypereosinophilic Syndrome, Polycythemia Vera, Atypical CML or CMML With Platelet Derived Growth Factor (PDGF-R) Fusion Genes, or Mastocytosis With Imatinib Mesylate (STI571)

Acute myeloid leukemia (AML), Myelodysplastic Syndromes (MDS): CR=Normalization peripheral blood \& bone marrow with 5% or less blasts; normo- or hypercellular marrow; Absolute Neutrophil Count (ANC) \> 1.0 x 10\^9/L, \& platelet count \>100 x 10\^9/L; or CR marrow=As per CR but platelet count \< 100 x 10\^9/L. Agnogenic myeloid metaplasia (AMM) \& CMML: CR=Absence of signs/symptoms of disease; White blood count between 1 to 10 x 10\^9/L with no peripheral blasts, promyelocytes, or myelocytes and normalization of bone marrow (\< 5% blasts in normocellular or hypercellular marrow) for 4+ weeks. PV: CR=normalization of hemoglobin/hematocrit without need for phlebotomies, disappearance all signs/symptoms of disease. HES: CR=disappearance of eosinophilia (\</=10%), disappearance signs/symptoms of disease. Mastocytosis: CR=disappearance of mast cell infiltrates in affected organs, decrease of serum tyrptase levels to \<20 ng/ml, \& disappearance of SM-associated organomegaly.

Time from response to disease progression, measuring length of the response in those participants who responded.

Overall survival defined as time from registration to disease progression or death from any cause.

Novartis Pharmaceuticals

Imatinib mesylate 400 mg orally daily, HES participants start with 100 mg orally daily.

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Acute Leukemia

Chronic myeloproliferative disorders (CMPD)

Chronic Myelomonocytic Leukemia (CMML)

Essential Thrombocythemia

Hypereosinophilic syndrome (HES)

Systemic mastocytosis (SM)

Myelodysplastic syndromes (MDS)

Myelofibrosis

Polycythemia Vera (PV)

Leukemia diagnosis and any subtype determination confirmed via bone marrow aspirate and/or biopsy, assessed prior to treatment.

Leukemia Diagnosis Categories

Hagop M Kantarjian,MD/Chair, Leukemia

Number of Participants With a Complete Response (CR)

Duration of Response

Overall Survival

Overall Study

Leukemia, Myeloid, Acute

Primary Myelofibrosis

Metaplasia

Blast Crisis

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Vatalanib

For 1 week prior to receipt of study combination regimen, all patients will receive single agent PTK 787 at dose specified for that dose level of the study combination regimen to allow stabilization of PTK 787 levels. Patients should not have a grade 3 or 4 PTK 787-related adverse events in order to begin study combination therapy with a imatinib on day 8. On Day 8, PTK 787 250 mg by mouth every day and imatinib 600 mg by mouth every day (for Acute Myelogenous Leukemia (AML), Chronic Myelogenous Leukemia- blastic phase (CML-BP) and imatinib 400 mg by mouth every day (for Agnogenic Myeloid Metaplasia (AMM). Length of therapy is four courses; each course equals 28 days. Patients assessed for response after each course.

For 1 week prior to receipt of study combination regimen, all patients will receive single agent PTK 787 at dose specified for that dose level of the study combination regimen to allow stabilization of PTK 787 levels. Patients should not have a grade 3 or 4 PTK 787-related adverse events in order to begin study combination therapy with a imatinib on day 8. PTK 787 250 mg by mouth for Days 1 - 7.

600 mg by mouth every day (for AML, CML-BP) for a 28 day cycle.

400 mg by mouth every day (for AMM) for a 28 day cycle.

For 1 week prior to receipt of the study combination regimen, all patients will receive single agent PTK 787 at the dose specified for that dose level of the study combination regimen to allow stabilization of PTK 787 levels.

Starting dose: 250 mg by mouth every day for a 28 day cycle.

PTK 787 (vatalanib)

The goal of this clinical research study is to find the highest safe doses of PTK 787 (vatalanib) and Gleevec (imatinib mesylate) that can be given to treat Chronic Myelogenous Leukemia-Blastic Phase (CML-BP), Refractory Acute Myelogenous Leukemia (AML), or Agnogenic Myeloid Metaplasia (AMM). Another goal is to see how effective this combination treatment is.

Rationale: The purpose of this study is to combine PTK-787, a potent orally vascular endothelial growth factor (VEGF) receptor inhibitor (in disorders where VEGF is known to be involved in the pathophysiology), with Imatinib mesylate (IM), a protein-tyrosine kinase inhibitor of abl, Bcr-Abl, platelet derived growth factor (PDGF), and c-Kit (in same disorders where these kinases are believed to be important). The potential synergy between oral agents that inhibit these kinases in disorders where each of the two agents have some, but inadequate, single agent activity is being studied in this protocol. We will also have an opportunity to assess if there is any correlation between response and individual kinase mutations e.g., c-Kit in patients with AML. If improved outcomes are observed, further studies will be indicated to investigate which, if either, agent is predominantly responsible for such a benefit - these studies will be facilitated by the availability of more potent e.g., (AMN107 as an abl inhibitor), (Bevacizumab, AG013736 as VEGF inhibitors) agents which will help to define the relative importance of the various inhibitory activities.

Objectives: To determine the maximum tolerated doses (MTD) and pharmacokinetics (PK) of PTK 787 and imatinib mesylate, when given in combination to patients with refractory acute myelogenous leukemia (AML), agnogenic myeloid metaplasia (AMM) and chronic myelogenous leukemia in blastic phase (CML-BP).

To determine the efficacy (response rate, survival, time to progression, time to treatment failure, duration of response) of the MTD in these study populations.

PTK 787 and Gleevec in Patients With AML, AMM, and CML-BP

Ph I/II Study of PTK 787 (Vatalanib) and Gleevec (Imatinib) in Patients With Refractory Acute Myelogenous Leukemia (AML), Agnogenic Myeloid Metaplasia (AMM), and Chronic Myelogenous Leukemia- Blastic Phase (CML-BP)

Time to response is defined as the period of time from the date of first study drug administration until the first objective documentation of response.

Lonafarnib

Participants in CHRONIC PHASE receive Gleevec 400 mg by mouth every day, and SCH66336 100 mg by mouth twice a day.

Participants in ACCELERATED OR BLASTIC PHASE receive Gleevec 600 mg by mouth every day, and SCH66336 100 mg by mouth twice a day.

Participants in CHRONIC PHASE receive Gleevec 400 mg by mouth every day, and SCH66336 100 mg by mouth twice a day.

Participants in ACCELERATED OR BLASTIC PHASE receive SCH66336 100 mg by mouth twice a day.

Participants in ACCELERATED OR BLASTIC PHASE receive SCH66336 100 mg by mouth twice a day.

Lonafarnib (SCH66336)

Participants in CHRONIC PHASE receive Gleevec 400 mg by mouth every day.

Participants in ACCELERATED OR BLASTIC PHASE receive Gleevec 600 mg by mouth every day.

Jorge E. Cortes, MD

The purpose of this study if to investigate the effect of lonafarnib (SCH66336) in combination with Gleevec in the treatment of CML.

Existing pre-clinical and clinical data suggest that SCH66336, a farnesyl transferase inhibitor,exhibits significant activity against CML cells, and in fact may have synergistic activity in combination with imatinib mesylate. Thus, the objectives to the study are (1) to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of lonafarnib (SCH66336), a farnesyl transferase inhibitor, in combination with imatinib mesylate (Gleevec) in patients with chronic phase, accelerated phase, and blast crisis CML; (2) to assess the pharmacokinetics of the combination of lonafarnib and Gleevec in these patients; and (3) to assess in a preliminary way the biologic activity of the combination of lonafarnib and Gleevec in these patients.

Study of Lonafarnib and Gleevec in Chronic Myelogenous Leukemia

Phase I Study of Lonafarnib (SCH66336) and Gleevec (Imatinib Mesylate) in Chronic Myelogenous Leukemia (CML)

Dose-Limiting Toxicity (DLT) defined as grade 3 or 4 non-hematologic toxicity (NCI common criteria, version 2.0). Grade 3 or 4 nausea and vomiting considered DLT only if uncontrolled by antiemetics. Grade 3 or 4 diarrhea considered DLT only if uncontrolled for 48 hours despite adequate antidiarrheal therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Preoperative and Postoperative Imatinib Mesylate Study in Patients With c-Kit Positive GIST	NCT00500188	Gastrointestina...	Imatinib Mesyla...	-	M.D. Anderson Cancer Center
Therapy of HES, PV, Atypical Chronic Myelocytic Leukemia (CML) or Chronic Myelomonocytic Leukemia (CMML), and Mastocytosis With Imatinib Mesylate	NCT00038675	Chronic Myelomo... Chronic Myeloid... Polycythemia Ve... Hypereosinophil... Mastocytosis	Imatinib Mesyla...	-	M.D. Anderson Cancer Center
PTK 787 and Gleevec in Patients With AML, AMM, and CML-BP	NCT00088231	Acute Myelogeno... Agnogenic Myelo... Chronic Myeloge...	Imatinib Mesyla... PTK 787 (vatala...	15 Years -	M.D. Anderson Cancer Center
Therapy of HES, PV, Atypical Chronic Myelocytic Leukemia (CML) or Chronic Myelomonocytic Leukemia (CMML), and Mastocytosis With Imatinib Mesylate	NCT00038675	Chronic Myelomo... Chronic Myeloid... Polycythemia Ve... Hypereosinophil... Mastocytosis	Imatinib Mesyla...	-	M.D. Anderson Cancer Center
Study of Lonafarnib and Gleevec in Chronic Myelogenous Leukemia	NCT00047502	Chronic Myeloge...	Lonafarnib (SCH... Imatinib Mesyla...	16 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for imatinib mesylate (gleevec)