A phase II study of dasatinib BMS-354825 in subjects with Chronic or advanced phase chronic myelogenous leukemia or philadelphia chromosome positive acute lymphoblastic leukemia who are resistant or intolerant to imatinib. - ND

• Conditions: Chronic phase,accelerated phase, myeloid and lymphoid phase chronic myeloid leukemia and Ph ALL who are resistan or intolerant to Imatinib; MedDRA version: 8.1Level: HLGTClassification code 10024324Term: Leukaemias

• Registration Number: EUCTR2006-001279-39-IT
• Lead Sponsor: Bristol Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-11-17
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Subjects must have had prior exposure to imatinib and have primary or acquired resistance or intolerance. Subjects can be pretreated with IFN, standard chemotherapy or high-dose chemotherapy and stem-cell transplantation. Imatinib may or may not be their most recent treatment prior to entering this study. Subjects known to have a T315I mutation are not be eligible. CP CML Subjects with a myeloproliferative disorder defined as Ph CP CML must meet all the following criteria 15 blasts in PB cells or BM 30 blasts promyelocytes in PB cells or BM 20 basophils in PB cells Platelets 8805; 100,000/mm or less if related to prior drug therapy No extra-medullar involvement except liver or spleen AD CML and Ph ALL Subjects with a myeloproliferative disorder defined as Ph or BCR-ABL AP CML or MyBP CML or LyBP CML or ALL. AP CML Subjects are considered to have AP CML if they meet at least one of the following criteria At least 15 to 30 blasts in PB or in BM A sum of the percent of blasts and promyelocytes in PB or the BM 8805; 30 with 30 blasts alone 8805; 20 basophils in PB or BM Platelets 100,000/mm3 unrelated to prior drug therapy Subjects may not have extra-medullary infiltrates of leukemic cells other than in spleen or liver. In addition, the following subjects will be considered to be part of the AP CML population even if they do not reach the above threshold values of blasts in PB or BM for accelerated phase i.e. chronic phase by hematologic criteria Subjects with clonal evolution e.g. 8, 19, der Ph , iso17q, but not -Y only Subjects with prior episode of AP who achieved a hematologic response and subsequently progressed MyBP and LyBP CML Subjects are considered to have Myeloid or Lymphoid BP CML if they meet at least one of the following criteria 8805; 30 myeloid or lymphoid blasts in PB or in BM Extra-medullary infiltrates of leukemic cells, other than in spleen or liver, with myeloid or lymphoid blast morphology Subjects with asymptomatic leptomeningeal leukemia are eligible. Ph ALL Subjects must have received prior imatinib and at least one prior standard induction consolidation chemotherapy regimen and not be eligible for immediate autologous or allogeneic stem cell transplantation. There is no minimum blasts in PB or BM required for recurrent Ph ALL. Subjects with asymptomatic leptomeningeal leukemia are eligible. Subjects characteristics 1 ECOG performance status PS score 0 2 in CP CML subjects 2 ECOG PS score 0 - 3 in AD CML and Ph ALL subjects See Appendix 1 3 Adequate hepatic function defined as 8722; total bilirubin 8804; 2.0 times the institutional ULN 8722; alanine aminotransferase ALT and aspartate aminotransferase AST 8804; 2.5 times the institutional ULN 4 Adequate renal function defined as 8722; serum creatinine 8804; 1.5 times the institutional ULN 5 Serum Na, K, Mg, P and total serum Ca or ionized Ca levels must be 8805; grade 1. Ideally, subjects with low K, Mg levels, total serum Ca and/or ionized Ca must be repleted before protocol entry. Age and Sex 6 Men and women, 18 years of age and older 7 Women of childbearing potential WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study WOCBP must have a negative serum or urine pregnancy test minimum sensitivity 25 IU/L or equivalent units of HCG within 72 hours

Exclusion Criteria

Sex and Reproductive Status 1 WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period of at least one month before and for at least 3 months after completion of the study medication. 2 WOCBP using a non-effective contraceptive method 3 Women who are pregnant or breastfeeding 4 Women with a positive pregnancy test on enrollment or prior to study drug administration. 5 Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period and for at least 3 months after completion of study medication. Medical History and Concurrent Diseases 6 A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy 7 Uncontrolled or significant cardiovascular disease, including A myocardial infarction within 6 months Uncontrolled angina within 3 months Congestive heart failure within 3 months Diagnosed or suspected congenital long QT syndrome Any history of clinically significant ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointe Prolonged QTcF interval 450 msec on pre-entry ECG Any history of second or third degree heart block may be eligible if the subject currently has a pacemaker Heart rate consistently 50 beats/minute on pre-entry ECG Uncontrolled hypertension 8 History of significant bleeding disorder unrelated to CML, including Diagnosed congenital bleeding disorder e.g., von Willebrand s disease Diagnosed acquired bleeding disorder within one year e.g., acquired anti-factor VIII antibodies Clinically significant bleeding from the GI tract within 6 months 9 Dementia or altered mental status that would prohibit the understanding or rendering of informed consent Physical and Laboratory Test Findings 10 Evidence of digestive dysfunction that would prevent administration of study therapy Prohibited Therapies and/or Medications 11 Subjects who received any of the following 8722; hydroxyurea within 2 days unless WBC 50,000/mm3 8722; imatinib, interferon, 6-mercaptopurine or cytarabine within 7 days 8722; any investigational agent or other antineoplastic agent within 14 days 12 Subjects currently taking drugs that are generally accepted to have a risk of causing Torsade de Pointe see Appendix 2 13 Subjects currently taking drugs that are potent CYP3A4 substrates, inhibitors or inducers see Appendixes 3, 4 and 5 Other Exclusion Criteria 14 Prisoners or subjects who are compulsorily detained involuntarily incarcerated for treatment of either a psychiatric or physical e.g., infectious disease illness must not be enrolled into this study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified