Panobinostat (LBH589) and Imatinib Mesylate in Treating Patients With Previously Treated Chronic Phase Chronic Myelogenous Leukemia

• Status: Completed
• Trial end date: 2014-08-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Panobinostat and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with imatinib in treating patients with previously treated chronic phase chronic myelogenous leukemia.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Histone Deacetylase Inhibitors; Imatinib Mesylate; Panobinostat

Criteria

Inclusion Criteria:

• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed

• CML CP patients who have been treated with and tolerated Imatinib for 1 year or more, have achieved at least major cytogenetic response and continue to be BCR-ABL positive (Patients should be receiving Imatinib at a dose of 400 daily at the time of entry into the study)

• ANC and PLT need to be in the normal range

• Serum albumin >= 3g/dL

• AST/SGOT and ALT/SGPT =< 2.5 x upper limit of normal (ULN)

• Serum bilirubin =< 1.5 x ULN

• Serum creatinine =< 1.5 x ULN or 24-hour creatinine clearance >= 50 ml/min

• Serum potassium >= lower limit of normal (LLN)

• Serum phosphorus >= LLN

• Serum total calcium (corrected for serum albumin) or serum ionized calcium >= LLN

• Serum magnesium >= LLN

• ECOG performance status of =< 2

Exclusion Criteria:

• Prior treatment with an HDAC inhibitor

• Patient who have been treated with Imatinib < 1 year or patients are currently being treated with Imatinib at a dose > 400 mg daily

• Impaired cardiac function including any one of the following: Screening ECG with a QTc > 450 msec; Patients with congenital long QT syndrome; History or presence of sustained ventricular tachycardia; Any history of ventricular fibrillation or torsades de pointes; Bradycardia defined as heart rate < 50 beats per minute (patients with a pacemaker and heart rate >= 50 beats per minute are eligible); Patients with a myocardial infarction or unstable angina within 6 months of study entry; Congestive heart failure (NY Heart Association class III or IV); Right bundle branch block and left anterior hemiblock (bifascicular block)

• Uncontrolled hypertension

• Concomitant use of drugs with a risk of prolonging the QT interval or inducing torsades de pointes

• Concomitant use of CYP3A4 inhibitors

• Patients with unresolved diarrhea > CTCAE grade 1

• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589

• Other concurrent severe and/or uncontrolled medical conditions

• Patients who have received chemotherapy, any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy

• Concomitant use of any other anti-cancer therapy or radiation therapy

• Patients being treated with Coumadin (unless patients who require anticoagulation can be switched to a low-molecular weight or standard heparin)

• Female patients who are pregnant or breast feeding or patients of reproductive potential not willing to use a double method of contraception including a barrier method (i.e. condom) during the study and 3 months after the end of treatment (Women of childbearing potential [WOCBP] must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589)

• Male patients whose sexual partners are WOCBP not willing to use a double method of contraception including condom during the study and 3 months after the end of treatment

• Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin

• Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required

• Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent