Rationale: DCC-2036 is a potent broad spectrum inhibitor of BCR-ABL kinase. Inhibition of BCR-ABL has been validated for effective treatment of chronic myeloid leukemia (CML). The emergence of mutant forms of BCR-ABL which resist inhibition by imatinib, dasatinib, and nilotinib is associated with loss of efficacy in treatment of the disease. DCC-2036 is a potent inhibitor of resistant mutants of BCR-ABL including the T315I mutation, and would therefore be expected to effectively treat patients who fail to respond to other BCR-ABL inhibitors. DCC-2036 also inhibits FLT3-ITD, TIE2, KDR, LYN and TRKA kinases. Purpose: to assess the safety and tolerability in patients after continuous administration of DCC-2036 and to determine recommended doses for the conduct of a Phase 2 efficacy trial.
Name: DCC-2036
Description: 150 mg BID tablets, continuous dosing of 28 day cyclesType: DrugDCC-2036
Single Group Assignment
There is one SNP
A Multicenter Phase 1 Clinical and Pharmacokinetic Study of DCC-2036 in Subjects With Leukemias (Ph+CML With T315I Mutation Only). --- T315I ---
Study Safety and Preliminary Efficacy of DCC-2036 in Patients With Leukemias (Ph+ CML With T315I Mutation) Rationale: DCC-2036 is a potent broad spectrum inhibitor of BCR-ABL kinase. --- T315I ---
DCC-2036 is a potent inhibitor of resistant mutants of BCR-ABL including the T315I mutation, and would therefore be expected to effectively treat patients who fail to respond to other BCR-ABL inhibitors. --- T315I ---
Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible: - Ph+ CML in Chronic Phase with T315I mutation - 18 years or older - The subject has an ECOG performance status of ≤ 2. - Adequate organ function as indicated by the following laboratory assessments performed within 14 days prior to the first dose of study drug Hepatic: Serum bilirubin ≤1.5 times upper limit (X ULN) of normal unless due to leukemic involvement or Gilbert's syndrome; aspartate aminotransferase or alanine aminotransferase ≤ 2.5 X ULN; alkaline phosphatase ≤ 2.5 X ULN Renal: Serum creatinine ≤ 1.5 X ULN or 24 hour creatinine clearance ≥ 50 mL/min - Female subjects of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin pregnancy test within 14 days prior to the start of study drug - Sexually active subjects who are fertile must agree to use an effective barrier method of contraception while on therapy and for 30 days following discontinuation of study drug. --- T315I ---
The following exceptions apply: i) Hydroxyurea is permitted at any time prior to study enrollment; ii) Glucocorticoids (natural or synthetic) are allowed up to 48 hours prior to the start of the study drug (with the exception of steroids for pre-medication and topical/nasal steroid use which are allowed at any time) - The subject has AP or BP-CML - Received immunosuppressive therapy ≤ 28 days prior to the first dose of study drug - NY Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure - Myocardial infarction within 3 months of the start of study drug - Active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant - Any other severe concurrent disease and/or uncontrolled medical conditions, which in the judgment of the investigator, could predispose subjects to unacceptable safety risks or compromise compliance with the protocol - Human immunodeficiency virus positive - If female, the subject is pregnant or lactating - Allergic or hypersensitive to any component of the investigational drug product Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible: - Ph+ CML in Chronic Phase with T315I mutation - 18 years or older - The subject has an ECOG performance status of ≤ 2. - Adequate organ function as indicated by the following laboratory assessments performed within 14 days prior to the first dose of study drug Hepatic: Serum bilirubin ≤1.5 times upper limit (X ULN) of normal unless due to leukemic involvement or Gilbert's syndrome; aspartate aminotransferase or alanine aminotransferase ≤ 2.5 X ULN; alkaline phosphatase ≤ 2.5 X ULN Renal: Serum creatinine ≤ 1.5 X ULN or 24 hour creatinine clearance ≥ 50 mL/min - Female subjects of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin pregnancy test within 14 days prior to the start of study drug - Sexually active subjects who are fertile must agree to use an effective barrier method of contraception while on therapy and for 30 days following discontinuation of study drug. --- T315I ---