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A Pilot Study of Oral Dasatinib in Subjects With MDS and Excess Marrow Blasts


N/A
18 Years
N/A
Not Enrolling
Both
Myelodysplastic Syndromes

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Trial Information

A Pilot Study of Oral Dasatinib in Subjects With MDS and Excess Marrow Blasts


Study Core Period:

The first 16 weeks after the initial dose of dasatinib is called the Study Core Period.
Patients who are eligible and chose to participate in this study should expect to take 100
mg of dasatinib daily for 8 weeks. If the study doctor believes that they have not achieved
a partial response after 8 weeks of treatment, the dose may be increased to 150 mg per day.
The study doctor may lower the dosage of dasatinib if the 100 mg treatment is too strong.
If the lower dose of dasatinib is still too strong, the study doctor may decide to take the
patient off of the study. The patient will continue to receive supportive care as needed
during the duration of the trial as well as after completion of the trial.

During the Study Core Period, participants will have a study visit every 4 weeks. Complete
Blood Counts (CBCs) will be obtained every 2 weeks for study purposes and disease
monitoring. Bone marrow aspiration and biopsy will be obtained at screening, and at 8 weeks
and 16 weeks of treatment for response assessment. Additional bone marrow aspirations and
biopsies may be obtained at any other time, to evaluate the disease process, at the doctor's
judgment. A bone marrow aspirate and biopsy must be done at the time of study
discontinuation.

Study Extension Period:

The time after the first 16 weeks of treatment is called the study extension period. If the
patient is responding to the treatment, does not experience disease progression or any
severe adverse events, the patient may continue dasatinib treatment for up to 48 weeks. If
patients continue after 48 weeks, they will be asked to enroll in a separate extension study
for future follow up.

During the Study Extension Period, participants will have a study visit every 4 weeks.
Complete Blood Counts (CBCs) will be obtained every 2 or 4 weeks for study purposes and
disease monitoring. Bone marrow aspiration and biopsy will be obtained every 16 weeks. A
bone marrow aspirate and biopsy must be done at the time of study discontinuation.


Inclusion Criteria:



- Documented diagnosis of MDS or Myeloproliferative Disorders (MPS/MPD) with blast
percentage > 10% in bone marrow, MDS/AML with <30% blasts:

- MDS [all World Health Organization (WHO) types] with blast percentage > 10% in
bone marrow

- Chronic myelomonocytic leukemia (CMML) with blast percentage > 10% in bone
marrow

- Myelodysplastic / Myeloproliferative (MDS/MPD) syndromes with blast percentage >
10% in bone marrow

- Acute myeloid leukemia with Multilineage Dysplasia (MDS/AML) with <30% blasts
and declined standard induction chemotherapy or deemed unfit for standard
induction chemotherapy

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2

- Previous therapy with Azacitidine or Decitabine with last dose at least 2 months
prior to first dose of dasatinib okay. Must be at least 4 weeks out from any previous
investigational therapy.

- Adequate Organ Function

- Total bilirubin < 2.0 times institutional Upper Limit of Normal (ULN)

- Hepatic enzymes (AST, ALT) ≤ 2.5 times institutional ULN

- Serum Na, K+, Mg2+, Phosphate and Ca2+≥ Lower Limit of Normal (LLN) [low
electrolyte levels must be repleted to all for entry]

- Serum Creatinine < 1.5 times ULN

- Prothrombin time (PT), partial thromboplastin time (PTT) Grade 0-1

- Able to take oral medication (Dasatinib must be swallowed whole. Tablets can be
dissolved in juice and then put down an NG/G tube or drank as a solution)

- Women of childbearing potential (WOCBP) must have Negative serum or urine pregnancy
test within 72 hours prior to start of study drug

- Persons of reproductive potential must agree to use adequate birth control throughout
treatment and at least 4 weeks after study drug is stopped

- Signed written informed consent

Exclusion Criteria:

- White blood count (WBC) >50,000 off hydroxyurea for >72 hours

- Malignancy [other than the one treated in this study] requiring radiotherapy or
systemic treatment within past 3 years

- Chemotherapy or any agent with activity in MDS or AML concurrent with the study.

- Chemotherapy for MDS or AML prior to enrollment not allowed other than Azacitidine or
Decitabine >2 months prior to first dose

- Concurrent medical condition which may increase the risk of toxicity, including:

- Pleural or pericardial effusion

- Serious medical condition, unstable medical co-morbidity, psychiatric illness
that will prevent subject from signing informed consent form or place them at
unacceptable risk if they participate

- Cardiac Symptoms, including:

- Uncontrolled angina, congestive heart failure or myocardial infarction (MI)
within 6 months

- Diagnosed congenital long QT syndrome

- History of clinically significant ventricular arrhythmias (such as ventricular
tachycardia, ventricular fibrillation, or Torsades de Pointes)

- Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)

- Hypokalemia or hypomagnesemia if cannot be corrected

- History of significant bleeding disorder unrelated to cancer, including:

- Congenital bleeding disorders

- Acquired bleeding disorder within 1 year

- Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding

- Concomitant Medications, consider the following prohibitions:

- Drugs generally accepted to have risk of causing Torsades de Pointes(Must
discontinue drug 7 days prior to starting dasatinib)

- Concomitant use of H2 blockers or proton pump inhibitors with dasatinib not
recommended. Use of antacids should be considered in place of H2 blockers or
proton pump inhibitors in patients receiving dasatinib therapy.

- On-going requirement for treatment with platelet function inhibitor or
anti-coagulation.

- Must discontinue St. Johns Wort while receiving dasatinib therapy

- Must agree that intravenous (IV) bisphosphonates be withheld for first 8 weeks
of Dasatinib therapy due to risk of hypocalcemia.

- May not be receiving any prohibited CYP3A4 inhibitors

- Women:

- Positive pregnancy test at baseline

- Pregnant or breastfeeding

- Prisoners or patients who are compulsorily detained for treatment of either
psychiatric or physical (e.g., infectious) illness

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Marrow Complete Remission (CR)

Outcome Description:

Complete remission (modified IWG); IWG = International MDS Working Group. Bone Marrow Response must last ≥4 weeks. Bone marrow evaluation: Bone marrow showing ≤5% myeloblasts with normal maturation of all cell lines.

Outcome Time Frame:

1 Year 4 Months

Safety Issue:

No

Principal Investigator

Alan List, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute

Authority:

United States: Institutional Review Board

Study ID:

MCC-15276

NCT ID:

NCT00624585

Start Date:

February 2008

Completion Date:

May 2012

Related Keywords:

  • Myelodysplastic Syndromes
  • MDS
  • MDS/MPD
  • MDS/AML
  • CMML
  • Excess Marrow Blasts
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612