Study of Oral Dasatinib in Subjects With Myelodysplastic Syndrome (MDS) and Excess Marrow Blasts

NCT00624585 | Completed Results

• 2 other identifiers: MCC-15276CA180-106
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to learn how patients with myelodysplastic syndrome (MDS) respond to the study drug dasatinib. The study drug, dasatinib, has been approved by the U.S. Food and Drug Administration (FDA) for treatment of leukemia, but has not been approved for the treatment of other kinds of cancer. The use of dasatinib in this study is considered experimental.

Conditions

Myelodysplastic Syndromes

Keywords

MDS; MDS/MPD; MDS/AML; CMML; Excess Marrow Blasts

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Marrow Complete Remission (CR)

  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.

  1 Year 4 Months

Secondary Outcomes (3)

• Number of Participants With Hematologic Improvement

  1 Year 4 Months

• Number of Participants With Partial Remission (PR)

  1 Year 4 Months

• Number of Participants With Stable Disease (SD)

  1 Year 4 Months

Study Arms (1)

Dasatinib Dose Escalation

EXPERIMENTAL

Patients will be started on dasatinib at a continuous oral daily dose of 100 mg per day. At 8 weeks, if the initial dose is well tolerated and patient has not achieved a partial response, the dose may be increased to 150 mg per day. All patients will be followed per protocol for a total core period of 16 weeks from the first dose. Responding patients will continue dasatinib treatment for up to 48 weeks in the absence of treatment failure, disease progression, limiting toxicity or death. Patients continuing after 48 weeks will be enrolled in a separate extension study for future follow up.

Drug: Dasatinib

Interventions

Dasatinib DRUG

DOSE ESCALATION OF DASATINIB AFTER 8 WEEKS IF ELIGIBLE * Dose Level and Dose of dasatinib: 1. Starting dose (1-8 weeks)= 100 mg orally (po) daily 2. +1 (\<8 weeks if no PR and well tolerated) = 150 mg po daily DOSE MODIFICATION OF DASATINIB * Dose Level and Dose of dasatinib: 1. Starting dose = 100 mg po daily 2. -1 = 70 mg po daily 3. -2 = 50 mg po daily OR * Dose Level and Dose of dasatinib: 1. Starting dose = 150 mg po daily 2. -1 = 120 mg po daily 3. -2 = 90 mg po daily 4. -3 = 50 mg po daily

Also known as: SPRYCEL®

Dasatinib Dose Escalation

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Alan F. List, Executive Vice President & President, Moffitt Medical Group
• Organization: H. Lee Moffitt Cancer Center and Research Institute

alan.list@moffitt.org

813-745-6086

Study Officials

• Alan List, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2008
• First Posted: February 27, 2008
• Study Start: February 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: December 16, 2013
• Results First Posted: June 25, 2012

Record last verified: 2012-05

Locations

US (1)