Leukemia, Myelomonocytic, Acute
Conditions
Keywords
Leukemia, Myelomonocytic, Acute, Erlotinib
Brief summary
This research study is looking for patients with newly diagnosed acute myeloid leukemia (AML), AML that has returned (relapsed), or it has not responded adequately to previous treatments. Treating certain patients with chemotherapy may not be to their benefit or may cause more harm than benefit. The purpose of this study is to find out what effects (good and bad) erlotinib has on patients and their AML.
Interventions
DRUGErlotinib
Erlotinib will be administered orally at 150 mg once a day, continuously. Each cycle will be 28 days and there will be no break between the cycles.
Sponsors
OSI Pharmaceuticals
Indiana University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of AML with no history of previous clonal/malignant hematologic disorders such as myelodysplastic syndromes or myeloproliferative disorders. * Newly diagnosed patients will be age 70 or older * Relapses patients will be age 60 or older any time following first relapse, if patient is not considered candidate/not interested in salvage chemotherapy. * Refractory disease patients will be age 18-59 who have failed at least 2 lines of conventional chemotherapy (1 induction and 1 salvage) * Patient must have discontinued all previous therapies for AML at least 14 days and recovered from the non-hematologic side effects of the therapy. * Laboratory tests must be within protocol-specified ranges * Patient must be able to swallow and tolerate oral medication.
Exclusion criteria
* Patients with known central nervous system (CNS) leukemia by spinal fluid cytology, flow cytometry or imaging. * History of antecedent pre-leukemic hematologic disorders such as myelodysplastic syndromes or myeloproliferative disorders. * Diagnosis of acute promyelocytic leukemia (APL) * Patients who require chronic anticoagulation, are current smokers or who are taking rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John's Wort are not eligible. * Patients with active corneal erosions or history of abnormal corneal sensitivity test. * Patients with serious illness such as: significant ongoing or active infection, New York Heart Association (NYHA) Grade II or greater congestive heart failure, unstable angina (anginal symptoms at rest), new onset angina (began within the last 3 months), myocardial infarction within the past 6 months, cardiac ventricular arrhythmias requiring anti-arrhythmic therapy, cerebrovascular accident within past 3 months, or psychiatric illness that would limit compliance with the study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (Defined as Partial Remission or Better) to 3 Months of Treatment With Erlotinib | 3 months of treatment with erlotinib | The percent of patients were shown as having a partial remission or better based on definitions of response in AML. Partial remission includes a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. Complete remission includes presence of less than 5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. The percent and 95% exact confidence intervals will be calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (up to One Year Follow up) in Patients Who Achieve a Complete Remission | 1 year after treatment discontinuation | The duration of response is from the time of response until failure or until the end of follow-up for the patients who received complete remission. Complete remission includes presence of less than 5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. |
| Treatment Related Adverse Events Grade 3 or Higher | up to 15 months | Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grading scale will be from 1 (mild) to 5 (causing death). This will determine the number of unique patients who had a treatment related (possible, probable or definite) adverse event that was graded 3 or greater. |
Other
| Measure | Time frame |
|---|---|
| Mechanistic Attributes of Erlotinib Hydrochloride in AML, Including Intracellular Quantitative Protein and Gene Expression Modifications and the in Vivo Effect of This Agent on the Differentiation of AML Blasts | Baseline; days 3, 4, 8, and 29 of course 1; and day 29 of courses 3, 6, 9, and 12 |
Countries
United States
Participant flow
Recruitment details
This protocol was based on getting 14 patients. Due to the lack of response, the study was stopped at 11 patients for this pilot study.
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib Erlotinib: Erlotinib will be administered orally at 150 mg once a day, continuously. Each cycle will be 28 days and there will be no break between the cycles. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 1 |
| Overall Study | Disease progression | 5 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Erlotinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 76.8 years STANDARD_DEVIATION 7.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 11 |
| serious Total, serious adverse events | 5 / 11 |
Outcome results
Primary
Overall Response Rate (Defined as Partial Remission or Better) to 3 Months of Treatment With Erlotinib
The percent of patients were shown as having a partial remission or better based on definitions of response in AML. Partial remission includes a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. Complete remission includes presence of less than 5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. The percent and 95% exact confidence intervals will be calculated.
Time frame: 3 months of treatment with erlotinib
Population: All patients enrolled and received treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Overall Response Rate (Defined as Partial Remission or Better) to 3 Months of Treatment With Erlotinib | 0 percentage of participants |
Secondary
Duration of Response (up to One Year Follow up) in Patients Who Achieve a Complete Remission
The duration of response is from the time of response until failure or until the end of follow-up for the patients who received complete remission. Complete remission includes presence of less than 5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells.
Time frame: 1 year after treatment discontinuation
Population: All patients enrolled and received treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erlotinib | Duration of Response (up to One Year Follow up) in Patients Who Achieve a Complete Remission | 0 months | Standard Deviation 0 |
Secondary
Treatment Related Adverse Events Grade 3 or Higher
Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grading scale will be from 1 (mild) to 5 (causing death). This will determine the number of unique patients who had a treatment related (possible, probable or definite) adverse event that was graded 3 or greater.
Time frame: up to 15 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib | Treatment Related Adverse Events Grade 3 or Higher | 0 participants |
Other Pre-specified
Mechanistic Attributes of Erlotinib Hydrochloride in AML, Including Intracellular Quantitative Protein and Gene Expression Modifications and the in Vivo Effect of This Agent on the Differentiation of AML Blasts
Time frame: Baseline; days 3, 4, 8, and 29 of course 1; and day 29 of courses 3, 6, 9, and 12