Dasatinib as Therapy for Myeloproliferative Disorders (MPDs)

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00255346
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 68
• Location: 1
• Arms: 5
• Actual Duration (Months): 135.6
• Patients Per Site Per Month: 0.5

Study Details

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
• 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: Nov 15, 2005
• Actual Primary Completion Date: Mar 3, 2017
• Actual Study Completion Date: Mar 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 Names: Sprycel
Experimental: MDS/CMML Dasatinib 70 mg orally twice daily.	Drug: Dasatinib (BMS-354825); 70 mg orally twice daily; Other Names: Sprycel
Experimental: HES/CEL Dasatinib 70 mg orally twice daily.	Drug: Dasatinib (BMS-354825); 70 mg orally twice daily; Other Names: Sprycel
Experimental: Primary myelofibrosis (PMF) Dasatinib 70 mg orally twice daily.	Drug: Dasatinib (BMS-354825); 70 mg orally twice daily; Other Names: Sprycel
Experimental: Systemic Mastocytosis (SM) Dasatinib 70 mg orally twice daily.	Drug: Dasatinib (BMS-354825); 70 mg orally twice daily; Other Names: Sprycel

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol and Statistical Analysis Plan - Jul 18, 2011

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00255346
• Other Study ID Numbers: 2004-0817; NCI-2012-01353
• First Posted: Nov 18, 2005
• Last Update Posted: May 6, 2019
• Last Verified: May 1, 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; Dasatinib

Study Results

Participant Flow

Recruitment Details	Sixty-Seven participants were registered and received the study medication for this study.

Arm/Group Title	Acute Myeloid Leukemia (AML)	MDS/CMML	HES/CEL	Primary Myelofibrosis (PMF)	Systemic Mastocytosis (SM)
Arm/Group Description	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily
Period Title: Overall Study
STARTED	10	6	8	11	33
COMPLETED	9	6	8	11	33
NOT COMPLETED	1	0	0	0	0

Baseline Characteristics

Arm/Group Title	Acute Myeloid Leukemia (AML)	MDS/CMML	HES/CEL	Primary Myelofibrosis (PMF)	Systemic Mastocytosis (SM)	Total
Arm/Group Description	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Total of all reporting groups
Overall Participants	10	6	8	11	33	68
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 30%	2 33.3%	5 62.5%	8 72.7%	28 84.8%	46 67.6%
>=65 years	7 70%	4 66.7%	3 37.5%	3 27.3%	5 15.2%	22 32.4%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	70	68	62	63	57	62
Sex: Female, Male (Count of Participants)
Female	3 30%	2 33.3%	3 37.5%	1 9.1%	19 57.6%	28 41.2%
Male	7 70%	4 66.7%	5 62.5%	10 90.9%	14 42.4%	40 58.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	1 3%	1 1.5%
White	10 100%	6 100%	8 100%	11 100%	31 93.9%	66 97.1%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	1 3%	1 1.5%
Region of Enrollment (participants) [Number]
United States	9 90%	6 100%	8 100%	11 100%	33 100%	67 98.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Acute Myeloid Leukemia (AML)	MDS/CMML	HES/CEL	Primary Myelofibrosis (PMF)	Systemic Mastocytosis (SM)
Arm/Group Description	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily
Measure Participants	9	6	8	11	33
Count of Participants [Participants]	1 10%	0 0%	1 12.5%	0 0%	2 6.1%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The number of participants analyzed for duration of response reflects the number of participants with a response for each arm.

Arm/Group Title	Acute Myeloid Leukemia (AML)	MDS/CMML	HES/CEL	Primary Myelofibrosis (PMF)	Systemic Mastocytosis (SM)
Arm/Group Description	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily
Measure Participants	1	0	1	0	2
Mean (Full Range) [Months]	NA	NA	13

Adverse Events

Time Frame	Through study completion, up to 10 years
Arm/Group Title	Dasatinib All Patient Groups
Arm/Group Description	Dasatinib 70 mg orally twice daily. Dasatinib (BMS-354825): 70 mg orally twice daily
All Cause Mortality
	Dasatinib All Patient Groups
	Affected / at Risk (%)	# Events
Total	2/68 (2.9%)
Serious Adverse Events
	Dasatinib All Patient Groups
	Affected / at Risk (%)	# Events
Total	2/68 (2.9%)
Blood and lymphatic system disorders
Hemorrhage CNS	1/68 (1.5%)	1
Cardiac disorders
Pericardial Effusion	1/68 (1.5%)	1
Infections and infestations
Skin Infection	1/68 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/68 (1.5%)	1
Other (Not Including Serious) Adverse Events
	Dasatinib All Patient Groups
	Affected / at Risk (%)	# Events
Total	67/68 (98.5%)
Blood and lymphatic system disorders
Edema	5/68 (7.4%)	5
Platelets/Hemoglobin	6/68 (8.8%)	6
Gastrointestinal disorders
Diarrhea	5/68 (7.4%)	5
Nausea/Vomiting	21/68 (30.9%)	21
General disorders
Fatigue	8/68 (11.8%)	8
Headache	12/68 (17.6%)	12
Pain	7/68 (10.3%)	7
Respiratory, thoracic and mediastinal disorders
Dyspnea	18/68 (26.5%)	18
Pleural Effusion	14/68 (20.6%)	14
Skin and subcutaneous tissue disorders
Rash	4/68 (5.9%)	4

Limitations/Caveats

The outcome measures were collected and reported by participant diagnosis group. The Other Adverse Events and Serious Adverse Events were collected and recorded as a group for all participants registered on the study.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.