Dasatinib as Therapy for Myeloproliferative Disorders (MPDs)

• 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: M.D. Anderson Cancer Center
• 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

• 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

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 :

1. 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 :

1. 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

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

Criteria

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.

Contacts and Locations

Locations

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

• 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 

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

• 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:

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