Evaluation of Response of Dasatinib to Treat Mastocytosis

NCT00979160 | Unknown Phase 2 DMC

• 1 other identifier: CA 180-287
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 12

Brief Summary

This is a multicenter, open-label, single arm phase II non-randomized study of dasatinib in which subjects with systemic mastocytosis (SM) will be treated with a continuous regimen of dasatinib. Upon completion of a treatment induction period, subjects will be treated with dasatinib at a dose of 100 mg per os (OS) once daily (QD).

Conditions

Systemic Mastocytosis

Outcome Measures

Primary Outcomes (1)

• 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.

  December 2011

Secondary Outcomes (3)

• To assess of the Time to Response (TTR), Duration of Response (DOR) and Progression-Free survival (PFS).

  December 2012

• To evaluate the changes in specific biological markers and molecular mutations.

  June 2012

• To evaluate the safety and toxicity of dasatinib in this population.

  December 2011

Study Arms (1)

Dasatinib

EXPERIMENTAL

Patient will be treat at a starting dose of 20mg once daily, that can be escalated up to 100mg once daily.

Drug: Dasatinib

Interventions

Dasatinib DRUG

Starting dosage 20mg once daily, that can be escalated up to 100mg once daily. Patient will remain on treatment for 12 months.

Also known as: BMS-354825-03

Dasatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 normal.
• 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.

You may not qualify if:

• 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 therapy.
• 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.

Sponsors & Collaborators

• Federico II University: lead
• University of Bologna: collaborator

Study Sites (12)

Istituto di ematologia "L e A Seragnoli" - Policlinico universitario Sant'Orsola-Malpighi

Bologna, 40138, Italy

Location

Dipartimento di Ematologia - S.O.D. di Ematologia Università degli Studi di Firenze - Azienda Ospedaliera Careggi

Florence, 50134, Italy

Location

Divisione di Ematologia Ospedale Niguarda Ca' Grande

Milan, 20162, Italy

Location

Divisione di Allergologia e Immunologia Clinica, Università Federico II

Napoli, 80131, Italy

Location

Divisione di Ematologia Università di Torino Ospedale San Luigi Gonzaga

Orbassano (TO), 10043, Italy

Location

Istituto di Ematologia Università degli Studi di Pavia - Policlinico S. Matteo IRCCS

Pavia, 27100, Italy

Location

Unità di Ematologia e Trapianto Osseo CROB, Centro di Riferimento Oncologico di Basilicata +39 0972 726729 Fax +30 0972 726217 e-mail: p.musto@crob.it

Rionero in Vulture (Pz), Italy

Location

Ematologia Tor Vergata University Hospital

Roma, 00133, Italy

Location

Divisione di Ematologia Policlinico Universitario "Agostino Gemelli"

Roma, 00168, Italy

Location

Ematologia e Trapianti Università degli Studi di Siena - Policlinico S. Maria alle Scotte

Siena, 53100, Italy

Location

Divisione di Ematologia e Trapianto Midollo Osseo Azienda Ospedaliero-Universitaria "Santa Maria della Misericordia"

Udine, 33100, Italy

Location

Sezione di Ematologia - Dipartimento di Medicina Clinica e Sperimentale Policlinico G.B.Rossi - Università degli Studi di Verona

Verona, 37134, Italy

Location

MeSH Terms

Conditions

Mastocytosis, Systemic

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mast Cell Activation Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Massimo Triggiani, MD

  Università Federico II

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Massimo Triggiani, prof.

CONTACT

+390817462218; triggian@unina.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 16, 2009
• First Posted: September 17, 2009
• Study Start: November 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2012
• Last Updated: September 18, 2009

Record last verified: 2009-09

Locations

IT (12)