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

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.

OBJECTIVES:

Primary

* To determine the safety and tolerability of LBH589 given in combination with imatinib mesylate in CML patients who are in Major Cytogenetic Remission (MCR) with residual BCR-ABL positive cells after at least 1 year of daily imatinib mesylate treatment.
* To determine the maximum tolerated dose (MTD) and dose-limiting toxicity of LBH589 given in combination with imatinib mesylate in CML patients.

Secondary

* To study the effect of LBH589 given in combination with imatinib mesylate on cytogenetic response status and BCR-ABL levels in CML patients in major cytogenetic remission on imatinib mesylate treatment.

Tertiary

* To study the effect of LBH589 given in combination with imatinib mesylate on residual BCR-ABL positive primitive progenitors in CML patients in major cytogenetic remission on imatinib mesylate treatment.

OUTLINE: This is dose-escalation study of panobinostat.

Patients receive oral panobinostat once daily on days 1, 3 and 5; 8, 10, and 12; 15, 17, and 19; and 22, 24, and 26. Patients also receive oral imatinib mesylate once daily on days 1-28. Treatment repeats every 21 or 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 month and then every 3 months for up to 1 year.

Eligibility 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