Myelogenous Leukemia, Chronic, Chronic Phase
Conditions
Keywords
Philadelphia chromosome positive, early chronic phase (diagnosis < 12 months), Chronic Myelogenous Leukemia, Chronic Phase, Chronic Myelogenous Leukemia, CML, Gleevec, STI571
Brief summary
The goal of this clinical research study is to see if higher doses of imatinib mesylate (Gleevec, STI571) can improve chronic myelogenous leukemia (CML) in chronic phase.
Detailed description
Imatinib mesylate is a new oral medication that blocks a protein that is responsible for CML Before treatment starts, patients will have a physical exam, blood tests, and a bone marrow study. The bone marrow will be removed with a large needle. Women able to have children will have a screening blood or urine test for pregnancy. Patients on this study will take 400 mg of imatinib twice daily (morning and evening). If you have side effects, the dose may be lowered. If you are taking less than 800 mg of imatinib, you can take your dose once per day or divided in two doses. Imatinib mesylate should be taken with a large glass of water. Bottles containing the tablets will be given to the patient every 6 months. Unused supplies must be returned at the end of the study. After completing 3 to 12 months of therapy, response to imatinib mesylate will be evaluated. If the response is good, treatment with imatinib mesylate alone will be continued. Treatment may be continued for up to 20 years, or as long as it is judged best to control the leukemia. Update: June 2010 Blood tests 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 necessary to check your disease. You must return to MD 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. If the leukemia cannot be found for 2 years or longer on the blood test called polymerase chain reaction (PCR) which is done to measure the amount of disease you have, your doctor may talk to you about stopping treatment with imatinib. If you and your doctor decide to stop your therapy, you will have a blood test for PCR done every 3 to 6 months. You do not need to return to MD Anderson to have this blood test done. You may have the blood taken by your local doctor and mailed to M. D. Anderson. If the leukemia is found again by the PCR blood test, your doctor may recommend that you restart treatment with imatinib. You may decide to stay on treatment with imatinib even if your PCR blood test does not show any sign of leukemia for 2 years or longer. This is an investigational study. Imatinib mesylate has been approved in CML. A total of 125 patients will take part in this study. All will be enrolled at MD Anderson.
Interventions
DRUGGleevec
400 mg orally twice 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
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients age 15 years or older with a diagnosis of Ph-positive or Bcr-positive CML in early chronic phase CML (diagnosis \< 12 months). Except for hydroxyurea, patients must have received no or minimal prior therapy, defined as less than 1 month of prior interferon (IFN-a) or ara-C. 2. Eastern Cooperative Oncology Group (ECOG) performance of 0-2 3. Serum bilirubin less than 2 mg%, serum creatinine less than 2mg% 4. Women of pregnancy potential must practice contraception. 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. 5. Patients must sign an informed consent indicating they are aware of the investigational nature of this study, in keeping with the policies of the hospital. 6. The definitions of CML phases are as follows: a) early chronic phase: time from diagnosis to therapy \< 12 months, late chronic phase: time from diagnosis to therapy \> 12 months; b) blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow; c) accelerated phase CML: presence of any of the following features: peripheral or marrow blasts 15% or more, peripheral or marrow basophils 20% or more, thrombocytopenia \<100 x 10(9)/L unrelated to therapy, documented extramedullary blastic disease outside liver or spleen due to past causes 7. The definitions of CML phases are as follows: clonal evolution defined as the presence of additional chromosomal abnormalities other than the Ph chromosome is part of accelerated phase CML. Ph chromosome variants or complex Ph chromosome translocations are not considered to indicate disease acceleration. We have recently found clonal evolution to have a variable prognostic impact and may be suppressed with IFN-a therapy. Hence these patients will be eligible if no other accelerated phase signs are present, and analyzed separately. 8. Inclusion of women and minorities: As per NIH policy, women and members of minorities will be included in this protocol as they are referred in the CML population. Their distribution is similar to the general referral profiles for CML: about 50% of CML patients are females and 25% to 30% are members of minorities. There are no exclusions of women or minorities based on the study objectives.
Exclusion criteria
1. New York Heart Association (NYHA) class 3-4 heart disease 2. Psychiatric disability (psychosis) 3. Pregnant or lactating females 4. Patients in late chronic phase, accelerated phase or blastic phase are excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Molecular Response of Complete or Partial Hematologic Remission | Response to imatinib mesylate evaluated after completing 3 - 12 months of therapy. | Complete Hematologic Remission (CHR): normalization \>4 weeks of bone marrow (\<5% blasts), peripheral blood with White Blood Cells (WBC) \<10 x 109/L & no peripheral blasts, promyelocytes or myelocytes; disappearance all signs/symptoms disease. Partial Hematologic Response (PHR) = CHR except persistence of immature cells (myelocytes, metamyelocytes), or splenomegaly \< 50% of pretreatment, or thrombocytosis \>450x109/L but \<50% of pretreatment. Hematologic surveys twice per year with bone aspirations at discretion of treating physician. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participant Complete Hematologic Remission (CHR) Classified | Response to imatinib mesylate evaluated after completing 3 - 12 months of therapy. | Number of participants with Complete Hematologic Remission (CHR): normalization \>4 weeks of bone marrow (\<5% blasts), peripheral blood with WBC \<10 x 109/L & no peripheral blasts, promyelocytes or myelocytes; disappearance all signs/symptoms disease. CHR further classified according to suppression of Philadelphia chromosome (Ph) by cytogenetics or i Fluorescence In Situ Hybridization (FISH): No cytogenetic response - Ph positive 100% of pretreatment value; Minor cytogenetic response - Ph positive 35-90% of pretreatment value; Partial cytogenetic response - Ph positive 1-34% of pretreatment value; Complete cytogenetic response - Ph positive 0%. Hematologic surveys twice per year with bone aspirations at discretion of treating physician. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: June 11, 2001 to April 25, 2003. All recruitment done in medical settings at University of Texas (UT) MD Anderson Cancer Center.
Pre-assignment details
Of the 117 participants enrolled, three were excluded before starting: two (2) withdrew from the study prior to initiation of treatment and one (1) was ineligible.
Participants by arm
| Arm | Count |
|---|---|
| Gleevec Gleevec 400 mg orally twice daily. | 114 |
| Total | 114 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
Baseline characteristics
| Characteristic | Gleevec |
|---|---|
| Age, Continuous | 48 years |
| Region of Enrollment United States | 114 participants |
| Sex: Female, Male Female | 43 Participants |
| Sex: Female, Male Male | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 59 / 114 |
| serious Total, serious adverse events | 45 / 114 |
Outcome results
Primary
Number of Participants With Molecular Response of Complete or Partial Hematologic Remission
Complete Hematologic Remission (CHR): normalization \>4 weeks of bone marrow (\<5% blasts), peripheral blood with White Blood Cells (WBC) \<10 x 109/L & no peripheral blasts, promyelocytes or myelocytes; disappearance all signs/symptoms disease. Partial Hematologic Response (PHR) = CHR except persistence of immature cells (myelocytes, metamyelocytes), or splenomegaly \< 50% of pretreatment, or thrombocytosis \>450x109/L but \<50% of pretreatment. Hematologic surveys twice per year with bone aspirations at discretion of treating physician.
Time frame: Response to imatinib mesylate evaluated after completing 3 - 12 months of therapy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gleevec | Number of Participants With Molecular Response of Complete or Partial Hematologic Remission | PHR | 0 participants |
| Gleevec | Number of Participants With Molecular Response of Complete or Partial Hematologic Remission | CHR | 110 participants |
Secondary
Participant Complete Hematologic Remission (CHR) Classified
Number of participants with Complete Hematologic Remission (CHR): normalization \>4 weeks of bone marrow (\<5% blasts), peripheral blood with WBC \<10 x 109/L & no peripheral blasts, promyelocytes or myelocytes; disappearance all signs/symptoms disease. CHR further classified according to suppression of Philadelphia chromosome (Ph) by cytogenetics or i Fluorescence In Situ Hybridization (FISH): No cytogenetic response - Ph positive 100% of pretreatment value; Minor cytogenetic response - Ph positive 35-90% of pretreatment value; Partial cytogenetic response - Ph positive 1-34% of pretreatment value; Complete cytogenetic response - Ph positive 0%. Hematologic surveys twice per year with bone aspirations at discretion of treating physician.
Time frame: Response to imatinib mesylate evaluated after completing 3 - 12 months of therapy.
Population: Analysis was of the 110 participants who achieved a CHR with a cytogenetic response as described in the outcome measure descriptions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gleevec | Participant Complete Hematologic Remission (CHR) Classified | No cytogenetic response | 0 participants |
| Gleevec | Participant Complete Hematologic Remission (CHR) Classified | Minor cytogenetic response | 1 participants |
| Gleevec | Participant Complete Hematologic Remission (CHR) Classified | Partial cytogenetic response | 4 participants |
| Gleevec | Participant Complete Hematologic Remission (CHR) Classified | Complete cytogenetic response | 105 participants |