Acute Myeloid Leukemia, Agnogenic Myeloid Metaplasia, Hypereosinophilic Syndrome, Leukemia, Myelomonocytic, Chronic, Mastocytosis, Myelodysplastic Syndromes, Myelofibrosis, Polycythemia Vera
Conditions
Keywords
targeted therapy, leukemia, Acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), Agnogenic myeloid metaplasia - myelofibrosis (MMM), Hypereosinophilic syndrome (HES), Polycythemia vera (PV), Mastocytosis, CMML
Brief summary
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.
Detailed description
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.
Interventions
70 mg orally twice daily
Sponsors
Bristol-Myers Squibb
M.D. Anderson Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients \>/= 18 years old who meet the following eligibility criteria 2. Patients must have one of the following hematopoietic malignancies: C-kit positive (10% or more BM or PB MNC positive by flow) acute myeloid leukemia (AML excluding acute promyelocytic leukemia) or myelodysplastic syndrome (MDS) of the following types: Refractory-relapse AML-MDS including those who fail to achieve Complete Response (CR) after the first cycle of induction; Second or subsequent AML-MDS refractory-relapse; Newly diagnosed AML-MDS patients over 60 years of age with karyotype other than t(15:17), inv16, t(8:21), who do not want chemotherapy. 3. (Con't from # 2) Patients with MDS who do not want chemotherapy as initial treatment, or who are not eligible for the treatments of higher priority. 4. Agnogenic myeloid metaplasia - myelofibrosis (MMM) 5. Hypereosinophilic syndrome (HES) 6. Polycythemia vera (PV) 7. Mastocytosis 8. Serum bilirubin less than 2mg%, serum creatinine less than 2mg% unless abnormality is considered due to hematologic malignancy by investigator. 9. Eastern Cooperative Oncology Group (ECOG) Performance Status \< 3 10. 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. 11. Women of pregnancy potential must practice an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential (WOCBP) (defined as not post-menopausal for 12 months or no previous surgical sterilization) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. 12. Continued from #11: In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of 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. 13. 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 relevant populations. There are no exclusions of women or minorities based on the study objectives. 14. New York Heart Association (NYHA) Class \< 3 15. Ph negative MPD including chronic myelomonocytic leukemia (CMML).
Exclusion criteria
1. Pregnant or breast-feeding women are excluded. 2. All WOCBP MUST have a negative pregnancy test prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant Response Rate | Baseline to completion of 4 week cycle or until disease progression | 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% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (Survival) | Baseline, once a week for a month, thereafter monthly, up to 10 years | Response date to loss of response or last follow up. |
Countries
United States
Participant flow
Recruitment details
Sixty-Seven participants were registered and received the study medication for this study.
Participants by arm
| Arm | Count |
|---|---|
| Acute Myeloid Leukemia (AML) Dasatinib 70 mg orally twice daily.
Dasatinib (BMS-354825): 70 mg orally twice daily | 10 |
| MDS/CMML Dasatinib 70 mg orally twice daily.
Dasatinib (BMS-354825): 70 mg orally twice daily | 6 |
| HES/CEL Dasatinib 70 mg orally twice daily.
Dasatinib (BMS-354825): 70 mg orally twice daily | 8 |
| Primary Myelofibrosis (PMF) Dasatinib 70 mg orally twice daily.
Dasatinib (BMS-354825): 70 mg orally twice daily | 11 |
| Systemic Mastocytosis (SM) Dasatinib 70 mg orally twice daily.
Dasatinib (BMS-354825): 70 mg orally twice daily | 33 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | MDS/CMML | HES/CEL | Primary Myelofibrosis (PMF) | Systemic Mastocytosis (SM) | Acute Myeloid Leukemia (AML) | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 3 Participants | 5 Participants | 7 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 5 Participants | 8 Participants | 28 Participants | 3 Participants | 46 Participants |
| Age, Continuous | 68 years | 62 years | 63 years | 57 years | 70 years | 62 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 8 Participants | 11 Participants | 31 Participants | 10 Participants | 66 Participants |
| Region of Enrollment United States | 6 participants | 8 participants | 11 participants | 33 participants | 9 participants | 67 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants | 19 Participants | 3 Participants | 28 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 10 Participants | 14 Participants | 7 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 68 |
| other Total, other adverse events | 67 / 68 |
| serious Total, serious adverse events | 2 / 68 |
Outcome results
Primary
Participant Response Rate
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%
Time frame: Baseline to completion of 4 week cycle or until disease progression
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acute Myeloid Leukemia (AML) | Participant Response Rate | 1 Participants |
| MDS/CMML | Participant Response Rate | 0 Participants |
| HES/CEL | Participant Response Rate | 1 Participants |
| Primary Myelofibrosis (PMF) | Participant Response Rate | 0 Participants |
| Systemic Mastocytosis (SM) | Participant Response Rate | 2 Participants |
Secondary
Duration of Response (Survival)
Response date to loss of response or last follow up.
Time frame: Baseline, once a week for a month, thereafter monthly, up to 10 years
Population: The number of participants analyzed for duration of response reflects the number of participants with a response for each arm.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Acute Myeloid Leukemia (AML) | Duration of Response (Survival) | NA Months |
| HES/CEL | Duration of Response (Survival) | NA Months |
| Systemic Mastocytosis (SM) | Duration of Response (Survival) | 13 Months |