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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00686218
First received: May 28, 2008
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
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
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of LBH589 in Combination With Imatinib Mesylate for Patients With Chronic Myeloid Leukemia in Cytogenetic Remission With Residual Disease Detectable by Q-PCR

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Maximum tolerated dose of histone deacetylase inhibitor LBH589 in combination with imatinib mesylate [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of histone deacetylase inhibitor LBH589 in combination with imatinib mesylate [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Effect of treatment with histone deacetylase inhibitor LBH589 in combination with imatinib mesylate on cytogenetic response status and BCR-Abl levels [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Effect of treatment with histone deacetylase inhibitor LBH589 in combination with imatinib mesylate on residual BCR-Abl positive primitive progenitors [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: May 2008
Study Completion Date: August 2014
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (panobinostat, imatinib mesylate)
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
Given orally
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Drug: panobinostat
Given orally
Other Names:
  • Faridak
  • HDAC inhibitor LBH589
  • histone deacetylase inhibitor LBH589
  • LBH589
Genetic: polymerase chain reaction
Testing
Genetic: protein expression analysis
Testing
Genetic: western blotting
Testing
Other: flow cytometry
Testing
Other: laboratory biomarker analysis
Testing
Other: pharmacological study
Testing

Detailed Description:

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00686218

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010-3000
South Pasadena Cancer Center
South Pasadena, California, United States, 91030
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Ravi Bhatia, MD City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00686218     History of Changes
Other Study ID Numbers: 07203, P30CA033572, NOVARTIS-CSTI571AUS275T, CDR0000596065, NCI-2010-00528
Study First Received: May 28, 2008
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
chronic phase chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Panobinostat
Imatinib
Histone Deacetylase Inhibitors
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014