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

Tracking Information

• First Submitted Date: November 16, 2005
• First Posted Date: November 18, 2005
• Results First Submitted Date: April 17, 2018
• Results First Posted Date: May 6, 2019
• Last Update Posted Date: May 6, 2019
• Actual Study Start Date: November 15, 2005
• Actual Primary Completion Date: March 3, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 2, 2019)

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%

• Original Primary Outcome Measures: Not Provided
• Change History: Complete list of historical versions of study NCT00255346 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: May 2, 2019)

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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Acute Myeloid Leukemia
• Myelodysplastic Syndromes
• Agnogenic Myeloid Metaplasia
• Myelofibrosis
• Hypereosinophilic Syndrome
• Polycythemia Vera
• Mastocytosis
• Leukemia, Myelomonocytic, Chronic

Intervention

Drug: Dasatinib (BMS-354825)

70 mg orally twice daily

Other Name: Sprycel

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 7, 2017): 68
• Original Enrollment (submitted: November 16, 2005): 120
• Actual Study Completion Date: March 3, 2017
• Actual Primary Completion Date: March 3, 2017 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00255346
• Other Study ID Numbers: 2004-0817; NCI-2012-01353 ( Registry Identifier: NCI CTRP )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Responsible Party: M.D. Anderson Cancer Center
• Study Sponsor: M.D. Anderson Cancer Center
• Collaborators: Bristol-Myers Squibb

Investigators

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

• PRS Account: M.D. Anderson Cancer Center
• Verification Date: May 2019