Oral LBH589 in Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL)

NCT01090973 | Terminated Phase 2 Results DMC

• 3 other identifiers: MCC-15971IRB # Pro00000102CLBH589B25T
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to find out the effects and the safety of an investigational study drug called LBH589 when given to people with relapsed or refractory chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL).

Conditions

Non-Hodgkin's Lymphoma

Keywords

relapsed; refractory; CLL; chronic lymphocytic leukemia; MCL; mantle cell lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Desired Response

  Investigators intended to assess the rate of overall and complete response by World Health Organization (WHO) classification in patients with relapsed or refractory aggressive mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). WHO Performance Scale Measures levels of patient capability: 0 Normal activity; 1 Symptoms, but nearly fully ambulatory; 2 Some bed time, but needs to be in bed \<50% of normal daytime; 3 Needs to be in bed \>50% of normal daytime; 4 Unable to get out of bed.

  8 weeks (2 cycles) unless treatment continues due to partial or complete response

Secondary Outcomes (6)

• Number of Participants With Complete Response (CR) and Partial Response (PR)

  8 weeks (2 cycles) unless treatment continues due to partial or complete response

• Response Duration

  8 weeks (2 cycles) unless treatment continues due to partial or complete response

• Progression Free Survival (PFS) Estimate

  8 weeks (2 cycles) unless treatment continues due to partial or complete response

• Number of Participants With Prolonged Corrected QT (QTc) Interval

  8 weeks (2 cycles) unless treatment continues due to partial or complete response

• Number of Participants With Improved Blood and Lymphatic Evaluation Results

  8 weeks (2 cycles) unless treatment continues due to partial or complete response

Study Arms (1)

Oral drug treatment

EXPERIMENTAL

LBH589 will be given orally (by mouth), 40 mg once-a-day, 3 times weekly every week on days 1, 3 \& 5, then 8, 10 \&12, then 15, 17 \& 19, then 22, 24 \& 26.

Drug: LBH589

Interventions

LBH589 DRUG

The LBH589 capsule(s) should be swallowed by mouth with a glass of water (8 ounces noncarbonated) in the morning. The daily dose of LBH589 should be taken at approximately the same time each day. Patients should avoid eating grapefruit, Seville (sour) orange or drinking grapefruit juice or Seville orange juice during the study. After 2 cycles of treatment, if patients do not demonstrate a partial response or complete response (all of the tumor is gone) to the therapy they will be removed from the study. If patients do obtain a partial (the tumor(s) have decreased in size or number but there are still tumors present) or complete response then treatment will continue until their disease progresses.

Also known as: panobinostat, HDAC Inhibitor

Oral drug treatment

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
• Patients must meet the following laboratory criteria (unless dysfunction is due to organ infiltration by lymphoma):
• ANC ≥ 1.5 x 10\^9/L
• Hemoglobin ≥ 9 g/dl
• Platelets ≥ 75 x 10\^9/L
• Calculated CrCl ≥50 mL/min (MDRD Formula)
• Total serum calcium ≥ LLN
• Total serum magnesium ≥ LLN
• Aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN
• Serum bilirubin ≤1.5 x ULN
• Serum potassium ≥ LLN
• Thyroid stimulating hormone (TSH) ≥ lower limit of normal (LLN) and free T4 within normal limits. Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
• Baseline multiple uptake gate acquisition scan (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
• Documented MCL by biopsy or CLL by biopsy or flow cytometry.

You may not qualify if:

• Prior histone deacetylase (HDAC), DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
• Peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 3
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
• Patients with congenital long QT syndrome
• History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with the Sponsor prior to enrollment)
• History of ventricular fibrillation or torsade de pointes
• Bradycardia defined as HR\< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.
• Screening 12 lead electrocardiogram (ECG) with a QTc \> 450 msec
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
• Other clinically significant heart disease (e.g., congestive heart failure (CHF) New York Heart Association (NYHA) class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LBH589
• Patients with diarrhea \> CTCAE grade 1
• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Recurrence; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell

Interventions

Panobinostat; Histone Deacetylase Inhibitors

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Limitations and Caveats

The study was abandoned after only one patient due to low accrual and the sponsor losing interest in the single-agent. The one patient had disease progression requiring more aggressive treatment and did not complete the study.

Results Point of Contact

• Title: Celeste Bello, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

celeste.bello@moffitt.org

813-745-8623

Study Officials

• Celeste Bello, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2010
• First Posted: March 23, 2010
• Study Start: March 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: December 16, 2013
• Results First Posted: March 28, 2012

Record last verified: 2012-01

Locations

US (1)