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Multicenter, Open-Label, Single Arm Phase II Clinical Trial of Dasatinib in the Treatment of Systemic Mastocytosis

Phase 2
18 Years
Not Enrolling
Systemic Mastocytosis

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Trial Information

Multicenter, Open-Label, Single Arm Phase II Clinical Trial of Dasatinib in the Treatment of Systemic Mastocytosis

Dasatinib may have clinical efficacy and is safe in subjects with SM. This Multicenter,
open-label, single arm Phase II study will investigate the clinical response rate in terms
of both B/C findings and mediator-related symptoms.

30 adult patients will be treated with a continuous regimen of dasatinib at a starting dose
of 20 mg administered orally (PO) once daily (QD), that can be escalated up to 100 mg QD at
the end of Week 3. Upon completion of a treatment induction period, subjects will be treated
with dasatinib at a daily dose of 100 mg PO QD. Patients will remain on dasatinib treatment
for 12 months unless disease progression, unacceptable toxicity or other reasons determine
treatment discontinuation. Subjects may continue receiving protocol therapy as long as they
are deriving a clinical benefit.

Additionally, all subjects will be followed until disease progression, death, or 12 months
beyond discontinuation from study treatment.

The total duration of the study is estimated to 36 months.

Inclusion Criteria:

- Signed Written Informed Consent

- Subjects with confirmed diagnosis of SM according to the WHO criteria and the
following must be met:

- All SM clinical variations, smoldering SM should have ≥ 2 B-findings and severe
mediator related symptoms.

- KIT mutation status on BM cells must be available at baseline or ≤ 6 months
prior to study entry.

- Subjects may have not prior treatment with chemotherapeutic regimen including
imatinib or have either failed a prior chemotherapeutic regimen including imatinib or
other agent.

- At least two weeks must have elapsed from the last dose of chemotherapy, hormonal
therapy, immunotherapy, biological therapy or investigational product and radiation
therapy, and subjects must have recovered to baseline or Grade ≤ 1 (NCI CTCAE,
version 3.0) from the toxicities resulting from any of those recent therapies prior
to the first dose of dasatinib.

- ECOG performance status of 0, 1 or 2.

- Subject must be willing and able to comply with scheduled visits, treatment schedule,
laboratory tests, and requirements of the study.

- Adequate liver and renal functions defined as:

- Total bilirubin ≤ 2 x upper limit of normal (ULN) or ≤ 4 ULN if the sole cause
of liver elevation is due to SM

- AST, ALT and alkaline phosphatase ≤ 2.5 x ULN, or ≤ 5 ULN if the sole cause of
liver elevation or bone compromise is due to SM

- Serum creatinine ≤ 2 x ULN

- Serum potassium and magnesium levels within institutional normal limits. Total serum
calcium or ionized calcium level must be greater than or equal to the lower limit of

- Men and women, ages 18 and older.

- Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up to 4 weeks after the
last dose of investigational product in such a manner that the risk of pregnancy is
minimized. WOCBP must have a negative serum or urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of
investigational product.

Exclusion Criteria:

- WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for
the entire study period and for up to at least 4 weeks after the last dose of
investigational product.

- Women who are pregnant or breastfeeding

- Indolent SM (presence of B-findings without severe mediator-related symptoms)

- Pericarditis, clinically significant pleural effusion or ascites within 12 months
prior to study entry not attributable to SM.

- Pulmonary infiltrates within 4 weeks prior to study entry or abnormal chest X-ray at
baseline not attributable to SM.

- Any surgical procedure, excluding central venous catheter placement or other minor
procedures (e.g. skin biopsy) within 14 days prior to initiation of dasatinib

- Presence of active bacterial, fungal or viral infections at study entry.

- Clinically significant cardiac disease (NYHA Class III or IV) including preexisting
arrhythmia, (such as ventricular tachycardia, ventricular fibrillation, or "Torsade
de Pointes"), myocardial infarction, uncontrolled angina within 6 months, congestive
heart failure, or cardiomyopathy.

- Abnormal QTcF interval prolonged ( ≥ 450 msec) after electrolytes have been corrected
on baseline ECG.

- Malabsorption syndrome not attributable to SM or uncontrolled (e.g. not corrected by
antimediator therapy) gastrointestinal toxicities (nausea, diarrhea, vomiting) NCI
CTCAE Grade = 2.

- Clinically-significant coagulation or platelet function disorder (eg, known von
Willebrand's disease).

- Prior or concurrent malignancy, except for the following:

- Adequately treated basal cell or squamous cell skin cancer.

- Cervical carcinoma in situ.

- Adequately treated Stage I or II cancer from which the subject is currently in
complete remission.

- Or any other cancer from which the subject has been disease-free for 3 years.

- Cytopenia(s): ANC <1000/L, or hemoglobin <10 g/dL, or platelets < 100.000/L at study
entry unless the pretreatment bone marrow exam and/or presence of disease-related
hypersplenism establish that the likely causes of the cytopenia(s) is related to SM.

- Other severe, acute, or chronic medical or psychiatric condition or laboratory
abnormality, serious uncontrolled medical disorder or active infection that may
increase the risk associated with study participation or study drug administration or
may interfere with the interpretation of study results and, in the judgment of the
investigator, would make the subject inappropriate for this study.

- Intolerance to dasatinib.

- Administration of hematopoietic growth factors within 14 days prior to study entry.

- Medications that are generally considered to have a risk of causing "Torsades de

- Current therapy with steroids must be tapered off within 14 days prior to the start
of study medication if it is anticipated that subjects can be tapered off these
drugs. Otherwise, for steroid-requiring subjects, investigators should attempt to
taper to the minimal dose possible at the time of initiation of dasatinib therapy.

- Prisoners or subjects who are involuntarily incarcerated

- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.

Type of Study:


Study Design:

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

Outcome Measure:

To assess the clinical response rate in terms of both B/C findings and mediator-related symptoms in subjects with SM who have been treated with dasatinib.

Outcome Time Frame:

December 2011

Safety Issue:


Principal Investigator

Massimo Triggiani, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Università Federico II


Italy: Ethics Committee

Study ID:

CA 180-287



Start Date:

November 2009

Completion Date:

December 2012

Related Keywords:

  • Systemic Mastocytosis
  • Mastocytosis
  • Urticaria Pigmentosa
  • Mastocytoma
  • Mastocytosis, Systemic