Dasatinib as Therapy for Myeloproliferative Disorders (MPDs)

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ClinicalTrials.gov Identifier: NCT00255346

Recruitment Status : Completed

First Posted : November 18, 2005

Results First Posted : May 6, 2019

Last Update Posted : May 6, 2019

Sponsor:

Collaborator:

Bristol-Myers Squibb

Information provided by (Responsible Party):

M.D. Anderson Cancer Center

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.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Agnogenic Myeloid Metaplasia Myelofibrosis Hypereosinophilic Syndrome Polycythemia Vera Mastocytosis Leukemia, Myelomonocytic, Chronic	Drug: Dasatinib (BMS-354825)	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	68 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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)
Actual Study Start Date :	November 15, 2005
Actual Primary Completion Date :	March 3, 2017
Actual Study Completion Date :	March 3, 2017

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: PDGFRA-associated chronic eosinophilic leukemia PDGFRB-associated chronic eosinophilic leukemia Core binding factor acute myeloid leukemia Cytogenetically normal acute myeloid leukemia Familial acute myeloid leukemia with mutated CEBPA Polycythemia vera Primary myelofibrosis Systemic mastocytosis

MedlinePlus related topics: Leukemia

Drug Information available for: Dasatinib

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic Syndromes Polycythemia Vera Chronic Myeloproliferative Disorders Myelofibrosis Chronic Myelomonocytic Leukemia Hypereosinophilic Syndrome Mastocytosis Mast Cell Activation Syndrome Myelodysplastic/myeloproliferative Disease

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Acute myeloid leukemia (AML) Dasatinib 70 mg orally twice daily.	Drug: Dasatinib (BMS-354825) 70 mg orally twice daily Other Name: Sprycel
Experimental: MDS/CMML Dasatinib 70 mg orally twice daily.	Drug: Dasatinib (BMS-354825) 70 mg orally twice daily Other Name: Sprycel
Experimental: HES/CEL Dasatinib 70 mg orally twice daily.	Drug: Dasatinib (BMS-354825) 70 mg orally twice daily Other Name: Sprycel
Experimental: Primary myelofibrosis (PMF) Dasatinib 70 mg orally twice daily.	Drug: Dasatinib (BMS-354825) 70 mg orally twice daily Other Name: Sprycel
Experimental: Systemic Mastocytosis (SM) Dasatinib 70 mg orally twice daily.	Drug: Dasatinib (BMS-354825) 70 mg orally twice daily Other Name: Sprycel

Outcome Measures

Primary Outcome Measures :

Participant Response Rate [ Time Frame: 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 Outcome Measures :

Duration of Response (Survival) [ Time Frame: Baseline, once a week for a month, thereafter monthly, up to 10 years ]
Response date to loss of response or last follow up.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00255346

Locations

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United States, Texas
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Bristol-Myers Squibb

Investigators

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Principal Investigator:	Hagop M Kantarjian, MD	M.D. Anderson Cancer Center

Study Documents (Full-Text)

Documents provided by M.D. Anderson Cancer Center:

Study Protocol and Statistical Analysis Plan [PDF] July 18, 2011

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

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Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00255346 History of Changes
Other Study ID Numbers:	2004-0817 NCI-2012-01353 ( Registry Identifier: NCI CTRP )
First Posted:	November 18, 2005 Key Record Dates
Results First Posted:	May 6, 2019
Last Update Posted:	May 6, 2019
Last Verified:	May 2019

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by M.D. Anderson Cancer Center:


targeted therapy leukemia Acute myeloid leukemia (AML) Myelodysplastic syndrome (MDS) Agnogenic myeloid metaplasia - myelofibrosis (MMM)	Hypereosinophilic syndrome (HES) Polycythemia vera (PV) Mastocytosis CMML

Additional relevant MeSH terms:

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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Preleukemia Polycythemia Vera Mastocytosis Leukemia, Myelomonocytic, Chronic Myelodysplastic Syndromes Primary Myelofibrosis Polycythemia Hypereosinophilic Syndrome Syndrome Metaplasia Disease Pathologic Processes	Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Myeloproliferative Disorders Bone Marrow Neoplasms Hematologic Neoplasms Neoplasms by Site Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Skin Diseases Immune Complex Diseases Hypersensitivity Immune System Diseases

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