Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Hypereosinophilic Syndrome, Mastocytosis, Polycythemia Vera
Conditions
Keywords
Leukemia, Chronic Myelomonocytic Leukemia, Chronic Myeloid Leukemia, Polycythemia Vera, Hypereosinophilic Syndrome, Mastocytosis, Imatinib Mesylate, Gleevec
Brief summary
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.
Detailed description
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.
Interventions
Imatinib mesylate 400 mg orally daily, and in HES patients start with imatinib mesylate 100 mg orally daily
Sponsors
Novartis Pharmaceuticals
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Participants must have 1 of the following hematopoietic malignancies: Hypereosinophilic syndrome (HES), Polycythemia vera (PV), Atypical CML or CMML with PDGF-R fusion genes, Mastocytosis, Serum bilirubin less than 2 mg%, serum creatinine less than 2 mg% unless abnormality is considered due to hematologic malignancy by investigator, Eastern Cooperative Oncology Group (ECOG) performance status \< 3, life expectancy \> 12 wks, 2. continued from above. Participants must sign informed consent indicating they are aware of the investigational nature of the study, in keeping with policies of the hospital, women of pregnancy potential must practice birth control. Women and men must continue birth control for the duration of the trial and at least 3 months after the last dose of study drug. Inclusion of women and minorities: As per NIH policy, women and members of minorities will be included as they are referred in the relevant populations. 3. continued from above. There are no exclusions of women or minorities based on the study objectives, New York Heart Association (NYHA) Class \<3.
Exclusion criteria
N/A
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Complete Response (CR) | after 2 months of therapy, up to 1 year. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | From response evaluation (first evaluation following 2 months therapy) to disease progression or death or until disease progression whichever occurs first, up to 12 years and 5 months | Time from response to disease progression, measuring length of the response in those participants who responded. |
| Overall Survival | From the start of therapy to death or disease progression, assessed up to 12 years and 5 months | Overall survival defined as time from registration to disease progression or death from any cause. |
Countries
United States
Participant flow
Recruitment details
All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Imatinib Mesylate Imatinib mesylate 400 mg orally daily, HES participants start with 100 mg orally daily. | 125 |
| Total | 125 |
Baseline characteristics
| Characteristic | Imatinib Mesylate |
|---|---|
| Age, Continuous | 56 years |
| Leukemia Diagnosis Categories Acute Leukemia | 10 participants |
| Leukemia Diagnosis Categories Chronic Myelomonocytic Leukemia (CMML) | 11 participants |
| Leukemia Diagnosis Categories Chronic myeloproliferative disorders (CMPD) | 7 participants |
| Leukemia Diagnosis Categories Essential Thrombocythemia | 2 participants |
| Leukemia Diagnosis Categories Hypereosinophilic syndrome (HES) | 20 participants |
| Leukemia Diagnosis Categories Myelodysplastic syndromes (MDS) | 7 participants |
| Leukemia Diagnosis Categories Myelofibrosis | 18 participants |
| Leukemia Diagnosis Categories Polycythemia Vera (PV) | 25 participants |
| Leukemia Diagnosis Categories Systemic mastocytosis (SM) | 25 participants |
| Region of Enrollment United States | 125 participants |
| Sex: Female, Male Female | 49 Participants |
| Sex: Female, Male Male | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 125 |
| other Total, other adverse events | 0 / 125 |
| serious Total, serious adverse events | 13 / 125 |
Outcome results
Primary
Number of Participants With a Complete Response (CR)
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 frame: after 2 months of therapy, up to 1 year.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imatinib Mesylate | Number of Participants With a Complete Response (CR) | Essential Thrombocythemia | 0 participants |
| Imatinib Mesylate | Number of Participants With a Complete Response (CR) | Acute Leukemia | 0 participants |
| Imatinib Mesylate | Number of Participants With a Complete Response (CR) | Chronic myeloproliferative disorders (CMPD) | 0 participants |
| Imatinib Mesylate | Number of Participants With a Complete Response (CR) | Chronic Myelomonocytic Leukemia (CMML) | 2 participants |
| Imatinib Mesylate | Number of Participants With a Complete Response (CR) | Hypereosinophilic syndrome (HES) | 3 participants |
| Imatinib Mesylate | Number of Participants With a Complete Response (CR) | Systemic mastocytosis (SM) | 4 participants |
| Imatinib Mesylate | Number of Participants With a Complete Response (CR) | Myelodysplastic syndromes (MDS) | 0 participants |
| Imatinib Mesylate | Number of Participants With a Complete Response (CR) | Myelofibrosis | 1 participants |
| Imatinib Mesylate | Number of Participants With a Complete Response (CR) | Polycythemia Vera (PV) | 2 participants |
Secondary
Duration of Response
Time from response to disease progression, measuring length of the response in those participants who responded.
Time frame: From response evaluation (first evaluation following 2 months therapy) to disease progression or death or until disease progression whichever occurs first, up to 12 years and 5 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Imatinib Mesylate | Duration of Response | 68 Months |
Secondary
Overall Survival
Overall survival defined as time from registration to disease progression or death from any cause.
Time frame: From the start of therapy to death or disease progression, assessed up to 12 years and 5 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Imatinib Mesylate | Overall Survival | 73.2 Months |