Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Skin and Connective Tissue Diseases

Rare 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

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myelodysplastic-Myeloproliferative Diseases

Bone Marrow Neoplasms

Hematologic Neoplasms

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

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

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Mitogens

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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

Imatinib Mesylate (Gleevec)

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

M.D. Anderson Cancer Center

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

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Philadelphia Chromosome

Mastocytosis, Systemic

Blast Crisis

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Translocation, Genetic

Chromosome Aberrations

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Systemic Mastocytosis

Lymphosarcoma

Nilotinib

Imatinib-resistant / intolerant PH+ CML-CP patients

Imatinib-resistant / intolerant PH+ CML-AP patients

Novartis Pharmaceuticlas

The purpose of this trial is to assess the efficacy, safety, tolerability, biologic activity, and pharmacokinetics of AMN107 in six groups of patients with one of the following conditions:

Relapsed/refractory Ph+ Acute lymphoblastic leukemia (ALL) (arm 1)

Group A - Imatinib failure only (arms 2, 3 and 4)

* imatinib-resistant or intolerant CML - Chronic Phase (CP)
* imatinib-resistant or intolerant CML - Accelerated Phase (AP)
* imatinib-resistant or intolerant CML - Blast Crisis (BC)

Group B - Imatinib and other TKI failure (arms 2, 3 and 4)

* imatinib-resistant or intolerant CML - Chronic Phase (CP)
* imatinib-resistant or intolerant CML - Accelerated Phase (AP)
* imatinib-resistant or intolerant CML - Blast Crisis (BC)

Hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) (arm 5)

Systemic mastocytosis (Sm) (arm 6)

A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies

A Phase IA/II Multicenter, Dose-escalation Study of Oral AMN107 on a Continuous Daily Dosing Schedule in Adult Patients With Imatinib-resistant/Intolerant CML in Chronic or Accelerated Phase or Blast Crisis, Relapsed/Refractory Ph+ ALL, and Other Hematologic Malignancies.

Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in bone marrow).

Hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count \<10 x 109/L, Platelet count \<450 x 109/L, Basophils \<5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes \< 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).

Hematological response was a primary outcome measure for Arm CML-AP with prior imatinib only.

Cytogenetic responses (CyRs) in CML are based on the percentage of Ph+ metaphases in bone marrow; a value of 0% Ph+ metaphases defines a complete cytogenetic response (CCyR) and \>0% to 35% defines a major cytogenetic response (MCyR). Achievement of CCyR is associated with a significant survival advantage in participants with CML-CP. MCyR was categorized as either CCyR or partial cytogenetic response (PCyR).

A Complete Hematologic Response (CHR) is obtained when all the following criteria are met: WBC ≤ institutional ULN; platelets ≤ 450,000/mm3; ≤20% basophils in peripheral blood; no blasts or promyelocytes in PB cells; \< 5% myelocytes plus metamyelocytes in PB cells; no extra-medullary involvement including no hepatomegaly or splenomegaly.

MMR was defined for participants who demonstrated a reduction in BCR-ABL/control gene % transcripts to ≤0.1% based on international scale. The control gene used may have been either BCR or ABL.

Time to Progression was defined as the time from the start of nilotinib to the earliest date of Disease Progression (PD), discontinuation due to PD or death.

Disease progression was defined as an increase in the number of circulating leukemic cells via cytogenetic assessment using real-time quantitative reverse transcriptase polymerase chain reaction (PCR).

OS was calculated for all participants as the time between the start of nilotinib and death. Participants were followed for survival after discontinuation, every 3 months, and were included in the analysis of OS. Censoring was at the date of the last contact for discontinued participants and followed up for survival.

Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

Safety set: All participants who received at least one dose of study medication and had at least one post baseline safety assessment.

Adult participants PH+ CML-CP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

CML-CP With Prior Imatinib Only

Adult participants Ph+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

CML-AP With Prior Imatinib Only

Adult participants Ph+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

CML-CP

Adult participants PH+ CML-AP without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

Adult participants PH+ CML-CP in addition to prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

Total

<35 years

≥35 to <55 years

≥55 to <65 years

≥65 years

Age, Customized

Study Director

Adult participants PH+ CML-AP (Accelerated Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

Full Analysis Set (FAS): All participants who received at least one dose of study medication

Number of Participants With Major Cytogenetic Response (MCyR)

Full Analysis Set (FAS): All participants who received at least one dose of study medication.

Number of Participants Confirmed Overall Hematological Response (Phase II)

Number of Participants With Overall Major Cytogenetic Responses (Phase II)

Number of Participants With Complete Hematologic Response (Phase II)

Full Analysis Set (FAS): All participants who received at least one dose of study medication.

Major molecular response was not an efficacy variable for participants who received the CML-CP with prior imatinib and other TKI (Group B E8)

Participants With (MMR) Major Molecular Response (Phase II)

Full Analysis Set (FAS): All participants who received at least one dose of study medication.

Time to progression was not an efficacy variable for participants who received the CML-CP with prior imatinib and other TKI (Group B E8).

Time to Progression (TTP) (Phase II)

Overall Survival (OS) (Phase II)

Serious Adverse Events

Adverse Events

Adult participants PH+ CML-CP ( Chronic Phase Chronic Myeloid Leukemia) without prior TKI treatment with either resistant / intolerant to Imatinib received 400 mg Nilotinib orally twice daily up to the end of treatment (September-2012).

Number of Participants With Adverse Events and Serious Adverse Events to Evaluate Long Term Safety

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Lung Neoplasms

Gastrointestinal Stromal Tumors

Hypersensitivity

Dermatofibrosarcoma

Fibrosarcoma

Neoplasms, Fibrous Tissue

Sarcoma

Dermatofibrosarcoma Protuberans

Soft Tissue Sarcoma

imatinib mesylate

This trial is for various types of malignancies which may depend on certain enzymes (tyrosine kinases) for growth. The objective of this study is to assess to what extent imatinib mesylate blocks these enzymes and to assess the effect on the malignancy.

Condition

Diverse malignancies either associated with or thought to be associated with activated tyrosine kinase enzymes including hypereosinophilic syndrome systemic mastocytosis chronic myelomonocytic leukaemia, dermatofibrosarcoma protuberans and other diseases.

Not included:

Patients with chronic myeloid leukemia, some other types of leukemias (abl-mutated) some types of gastrointestinal stromal tumours (c-KIT-positive), some systemic mastocytosis (if c-KIT D816V mutation), brain, prostate, breast or lung cancers.

Imatinib Mesylate in Patients With Various Types of Malignancies Involving Activated Tyrosine Kinase Enzymes

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Primary Myelofibrosis

Metaplasia

Precancerous Conditions

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Dasatinib

Dasatinib (BMS-354825)

Hagop M Kantarjian, MD

The goal of this clinical research study is to learn if dasatinib can help to control myeloproliferative disorders. The safety and tolerability of dasatinib will also be studied.

Dasatinib is an experimental anti-cancer drug that is designed to block the function of BCR-ABL, which is the abnormal protein responsible for causing leukemia in some cells.

If you are found to be eligible to take part in this study, you will take dasatinib by mouth twice a day. If you have mastocytosis, you will take dasatinib by mouth once a day. A treatment cycle will be defined as 4 weeks (28 days) + 7 days. You will be instructed to take dasatinib in the morning (between about 6:00 a.m.-10:00 a.m.) and in the evening (between about 6:00 p.m.-10:00 p.m.).

Blood tests (about 2 - 3 teaspoons) will be done once a week for a month, then once a month for 5 years, then once every 6 months (if your doctor thinks it is needed) for the remainder of your treatment on this study. A bone marrow biopsy will be done after 1-2 months of therapy to document response.

Dasatinib will be given for as long as you are responding. You will be taken off study if the disease gets worse or intolerable side effects occur.

This is an investigational study. Dasatinib is authorized for use in research only. A total of 145 patients will take part in this study. All will be treated at MD Anderson.

Dasatinib as Therapy for Myeloproliferative Disorders (MPDs)

Therapy of Myeloid Metaplasia-Myelofibrosis, Atypical Chronic Myeloid or Myelomonocytic Leukemia, C-Kit Positive Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (AML-MDS), Hypereosinophilic Syndrome, Polycythemia Vera, and Mastocytosis With Dasatinib (BMS-354825)

Response Rate is complete response plus partial response (CR+PR) for each disease category. Response Evaluation Criteria are as follows:

Systemic Mastocytosis (SM): CR is the improvement of C-Findings, Tryptase \<20, and no organomegaly. PR is the improvement of C-Findings.

Acute Myeloid Leukemia (AML)/MDS and CMML: CR is bone marrow blasts \</= 5%, absolute neutrophil count (ANC) \>/= 1000 and platelets \>/= 100. PR is bone marrow blasts 6-25% but decreased by \> 50% and absolute neutrophil count, absolute neutrophil count (ANC) \>/= 1000 and platelets \>/= 100.

Primary Myelofibrosis (PMF): CR is bone marrow blasts \</= 5%, absolute neutrophil count (ANC) \>/= 1000 and platelets \>/= 100. CR is PR plus one or more of the following: ANC \>/= 1000, decreased platelets by 50%, hemoglobin increase of 2g/dl or reduction splenomegaly and/or hepatomegaly by 50%.

HES/CEL: CR is disappearance of eosinophilia \</= 10%, PR is reduction of eosinophilia by \>/= 50%

Response date to loss of response or last follow up.

Bristol-Myers Squibb

Dasatinib 70 mg orally twice daily.

Dasatinib (BMS-354825): 70 mg orally twice daily

Dasatinib All Patient Groups

Acute Myeloid Leukemia (AML)

MDS/CMML

HES/CEL

Primary Myelofibrosis (PMF)

Systemic Mastocytosis (SM)

Age, Categorical

Race (NIH/OMB)

The outcome measures were collected and reported by participant diagnosis group. The Other Adverse Events and Serious Adverse Events were collected and recorded as a group for all participants registered on the study.

Hagop Kantarjian, MD/Department Chair

Participant Response Rate

The number of participants analyzed for duration of response reflects the number of participants with a response for each arm.

Duration of Response (Survival)

Hematinics

Liver Extracts

Bilirubin

The dosing regimen to be used initially (400 mg po qd in adults and 260 mg/m2/day in children with food and a glass of water) is identical to that recommended by the FDA for the treatment of the chronic phase of chronic myelogenous leukemia (CML) (Prod Info Gleevec ). In patients with ANC \<1500/mm3, platelet counts \< 75,000mm3 or abnormal liver function tests (ALT or AST \> 2.5 or bilirubin \> 3 times the upper limit of normal), the starting dose will be reduced to 300 mg po qD.

Imatinib

The dosing regimen to be used initially (15 mg po bid) is identical to that recommended by the FDA for the treatment of myelofibrosis with platelet counts of 100-200,000/mm3 (Prod Info ruxolitinib). In patients with platelet counts \<100,000/mm3, moderate renal impairment (CrCl \<60 mL/min) or abnormal liver function tests (ALT or AST \> 2.5 or bilirubin \> 3 times the upper limit of normal), the starting dose will be reduced to 10 mg bid. The recommended guidelines for dose adjustment during therapy and discontinuation of therapy in myelofibrosis will be followed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies	NCT00109707	Chronic Myeloge... Acute Lymphobla... Hypereosinophil... Systemic Mastoc...	Nilotinib	18 Years -	Novartis
Imatinib Mesylate in Patients With Various Types of Malignancies Involving Activated Tyrosine Kinase Enzymes	NCT00171912	Hypereosinophil... Systemic Mastoc... Chronic Myelomo... Dermatofibrosar...	imatinib mesyla...	16 Years - 80 Years	Novartis
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
Dasatinib as Therapy for Myeloproliferative Disorders (MPDs)	NCT00255346	Acute Myeloid L... Myelodysplastic... Agnogenic Myelo... Myelofibrosis Hypereosinophil... Polycythemia Ve... Mastocytosis Leukemia, Myelo...	Dasatinib (BMS-...	18 Years -	M.D. Anderson Cancer Center
Dasatinib as Therapy for Myeloproliferative Disorders (MPDs)	NCT00255346	Acute Myeloid L... Myelodysplastic... Agnogenic Myelo... Myelofibrosis Hypereosinophil... Polycythemia Ve... Mastocytosis Leukemia, Myelo...	Dasatinib (BMS-...	18 Years -	M.D. Anderson Cancer Center
Dasatinib as Therapy for Myeloproliferative Disorders (MPDs)	NCT00255346	Acute Myeloid L... Myelodysplastic... Agnogenic Myelo... Myelofibrosis Hypereosinophil... Polycythemia Ve... Mastocytosis Leukemia, Myelo...	Dasatinib (BMS-...	18 Years -	M.D. Anderson Cancer Center
Tyrosine Kinase Inhibition to Treat Myeloid Hypereosinophilic Syndrome	NCT00044304	Eosinophilic My... Hypereosinophil...	Imatinib Ruxolitinib	2 Years -	National Institutes of Health Clinical Center (CC)
Tyrosine Kinase Inhibition to Treat Myeloid Hypereosinophilic Syndrome	NCT00044304	Eosinophilic My... Hypereosinophil...	Imatinib Ruxolitinib	2 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for hypereosinophilic syndrome