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Dasatinib as Therapy for Myeloproliferative Disorders (MPDs)

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndromes, Agnogenic Myeloid Metaplasia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dasatinib (BMS-354825)
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring targeted therapy, leukemia, Acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), Agnogenic myeloid metaplasia - myelofibrosis (MMM), Hypereosinophilic syndrome (HES), Polycythemia vera (PV), Mastocytosis, CMML

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients >/= 18 years old who meet the following eligibility criteria 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. (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. Agnogenic myeloid metaplasia - myelofibrosis (MMM) Hypereosinophilic syndrome (HES) Polycythemia vera (PV) Mastocytosis Serum bilirubin less than 2mg%, serum creatinine less than 2mg% unless abnormality is considered due to hematologic malignancy by investigator. Eastern Cooperative Oncology Group (ECOG) Performance Status < 3 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. 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. 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. 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. New York Heart Association (NYHA) Class < 3 Ph negative MPD including chronic myelomonocytic leukemia (CMML). Exclusion Criteria: Pregnant or breast-feeding women are excluded. 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.

Sites / Locations

  • The University of Texas M.D. Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Acute myeloid leukemia (AML)

MDS/CMML

HES/CEL

Primary myelofibrosis (PMF)

Systemic Mastocytosis (SM)

Arm Description

Dasatinib 70 mg orally twice daily.

Dasatinib 70 mg orally twice daily.

Dasatinib 70 mg orally twice daily.

Dasatinib 70 mg orally twice daily.

Dasatinib 70 mg orally twice daily.

Outcomes

Primary Outcome Measures

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%

Secondary Outcome Measures

Duration of Response (Survival)
Response date to loss of response or last follow up.

Full Information

First Posted
November 16, 2005
Last Updated
March 31, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00255346
Brief Title
Dasatinib as Therapy for Myeloproliferative Disorders (MPDs)
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
November 15, 2005 (Actual)
Primary Completion Date
March 3, 2017 (Actual)
Study Completion Date
March 3, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndromes, Agnogenic Myeloid Metaplasia, Myelofibrosis, Hypereosinophilic Syndrome, Polycythemia Vera, Mastocytosis, Leukemia, Myelomonocytic, Chronic
Keywords
targeted therapy, leukemia, Acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), Agnogenic myeloid metaplasia - myelofibrosis (MMM), Hypereosinophilic syndrome (HES), Polycythemia vera (PV), Mastocytosis, CMML

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acute myeloid leukemia (AML)
Arm Type
Experimental
Arm Description
Dasatinib 70 mg orally twice daily.
Arm Title
MDS/CMML
Arm Type
Experimental
Arm Description
Dasatinib 70 mg orally twice daily.
Arm Title
HES/CEL
Arm Type
Experimental
Arm Description
Dasatinib 70 mg orally twice daily.
Arm Title
Primary myelofibrosis (PMF)
Arm Type
Experimental
Arm Description
Dasatinib 70 mg orally twice daily.
Arm Title
Systemic Mastocytosis (SM)
Arm Type
Experimental
Arm Description
Dasatinib 70 mg orally twice daily.
Intervention Type
Drug
Intervention Name(s)
Dasatinib (BMS-354825)
Other Intervention Name(s)
Sprycel
Intervention Description
70 mg orally twice daily
Primary Outcome Measure Information:
Title
Participant Response Rate
Description
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
Secondary Outcome Measure Information:
Title
Duration of Response (Survival)
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients >/= 18 years old who meet the following eligibility criteria 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. (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. Agnogenic myeloid metaplasia - myelofibrosis (MMM) Hypereosinophilic syndrome (HES) Polycythemia vera (PV) Mastocytosis Serum bilirubin less than 2mg%, serum creatinine less than 2mg% unless abnormality is considered due to hematologic malignancy by investigator. Eastern Cooperative Oncology Group (ECOG) Performance Status < 3 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. 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. 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. 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. New York Heart Association (NYHA) Class < 3 Ph negative MPD including chronic myelomonocytic leukemia (CMML). Exclusion Criteria: Pregnant or breast-feeding women are excluded. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hagop M Kantarjian, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Texas M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website

Learn more about this trial

Dasatinib as Therapy for Myeloproliferative Disorders (MPDs)

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