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

NCT00686218 | Completed Phase 1 DMC

• 5 other identifiers: 07203P30CA033572NOVARTIS-CSTI571AUS275TCDR0000596065NCI-2010-00528
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Leukemia

Keywords

chronic phase chronic myelogenous leukemia

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of histone deacetylase inhibitor LBH589 in combination with imatinib mesylate

  1 month

• Safety and tolerability of histone deacetylase inhibitor LBH589 in combination with imatinib mesylate

  4 months

Secondary Outcomes (2)

• Effect of treatment with histone deacetylase inhibitor LBH589 in combination with imatinib mesylate on cytogenetic response status and BCR-Abl levels

  4 months

• Effect of treatment with histone deacetylase inhibitor LBH589 in combination with imatinib mesylate on residual BCR-Abl positive primitive progenitors

  4 months

Study Arms (1)

Treatment (panobinostat, imatinib mesylate)

EXPERIMENTAL

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.

Drug: imatinib mesylate; Drug: panobinostat; Genetic: polymerase chain reaction; Genetic: protein expression analysis; Genetic: western blotting; Other: flow cytometry; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

imatinib mesylate DRUG

Given orally

Also known as: CGP 57148, Gleevec, Glivec

Treatment (panobinostat, imatinib mesylate)

panobinostat DRUG

Given orally

Also known as: Faridak, HDAC inhibitor LBH589, histone deacetylase inhibitor LBH589, LBH589

Treatment (panobinostat, imatinib mesylate)

polymerase chain reaction GENETIC

Testing

Treatment (panobinostat, imatinib mesylate)

protein expression analysis GENETIC

Testing

Treatment (panobinostat, imatinib mesylate)

western blotting GENETIC

Testing

Treatment (panobinostat, imatinib mesylate)

flow cytometry OTHER

Testing

Treatment (panobinostat, imatinib mesylate)

laboratory biomarker analysis OTHER

Testing

Treatment (panobinostat, imatinib mesylate)

pharmacological study OTHER

Testing

Treatment (panobinostat, imatinib mesylate)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010-3000, United States

Location

South Pasadena Cancer Center

South Pasadena, California, 91030, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Chronic-Phase

Interventions

Imatinib Mesylate; Panobinostat; Polymerase Chain Reaction; Blotting, Western; Flow Cytometry

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acid Amplification Techniques; Genetic Techniques; Investigative Techniques; Electrophoresis; Chemistry Techniques, Analytical; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry

Study Officials

• Ravi Bhatia, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2008
• First Posted: May 29, 2008
• Study Start: May 1, 2008
• Primary Completion: March 1, 2013
• Study Completion: August 1, 2014
• Last Updated: August 15, 2014

Record last verified: 2014-08

Locations

US (3)