A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin's Lymphoma

November 9, 2017 updated by: Ohio State University Comprehensive Cancer Center
This phase II trial studies how well giving panobinostat together with lenalidomide works in treating patients with relapsed or refractory Hodgkin lymphoma. Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving panobinostat together with lenalidomide may be an effective treatment for Hodgkin lymphoma

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES: I. Determine the overall response rate (ORR), including complete responses (CR) and partial responses (PR), with combined lenalidomide and panobinostat in patients with relapsed or refractory Hodgkin's lymphoma. SECONDARY OBJECTIVES: I. Assess the safety and tolerability of combined lenalidomide and panobinostat in patients with previously treated Hodgkin's lymphoma. II. Determine progression-free survival (PFS) in patients with previously treated Hodgkin's lymphoma receiving combined lenalidomide and panobinostat. III. Evaluate changes in natural killer (NK) cell number and function, plasma cytokines, gene expression profile of peripheral blood, and plasma proteins via proteomics, before, during, and after lenalidomide and panobinostat therapy. IV. Determine levels of histone acetylation before and after treatment with panobinostat. V. Determine the pharmacokinetics of lenalidomide in the presence of panobinostat. VI. To collect deoxyribonucleic acid (DNA) samples for potential later analysis of associations between outcomes and polymorphisms in genes coding for drug metabolizing enzymes, transporters and molecular targets of lenalidomide or panobinostat. OUTLINE: Patients receive panobinostat orally (PO) on days 1, 3, and 5 of weeks 1-4 and lenalidomide PO on days 1-7 of weeks 1-3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at least every 3 months for 2 years, and then every 6 months for 3-5 years

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed classical or lymphocyte predominant Hodgkin's lymphoma that is relapsed or refractory after at least one prior chemotherapy; patients with Hodgkin's lymphoma may have one of the following World Health Organization (WHO) subtypes:

    • Nodular sclerosis Hodgkin's lymphoma
    • Mixed cellularity Hodgkin's lymphoma
    • Lymphocyte-rich Hodgkin's lymphoma
    • Lymphocyte-deplete Hodgkin's lymphoma
    • Nodular Lymphocyte-predominant Hodgkin's lymphoma

  • Patients must have relapsed or progressed after at least one prior cytotoxic chemotherapy

    • Previous autologous or allogeneic stem cell transplantation is permitted
    • Previous treatment with either single agent panobinostat or lenalidomide is permitted
  • Absolute neutrophil count (ANC) >= 1200/μL
  • Platelets >= 100,000/μl
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit normal (ULN)
  • Serum bilirubin =< 1.5 x ULN
  • Calculated creatinine clearance >= 60ml/min by Cockcroft-Gault estimation of CrCI

  • Measurable Disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable; lesions that are considered non-measurable include the following:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Bone marrow involvement (involvement by non-Hodgkin lymphoma should be noted)
  • Baseline multi gated acquisition (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) >= 45%
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Able to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to starting Cycle 1 of lenalidomide (prescriptions must be filled within 7 days as required by RevAssist) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant of aspirin or at increased risk of venous thrombosis may use warfarin or low molecular weight heparin)

Exclusion Criteria:

  • Patients who are candidates for high dose chemotherapy and autologous stem cell transplantation with curative intent should not be enrolled
  • Patients with active central nervous system (CNS) lymphoma
  • Use of valproic acid for any medical condition while receiving protocol treatment or within 5 days prior to first panobinostat dose

  • Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:

    • History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment)
    • Any history of ventricular fibrillation or Torsade de Pointes
    • Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm
    • Screening electrocardiogram (ECG) with a QTc > 450 msec
    • Right bundle branch block + left anterior hemiblock (bifascicular block)
    • Patients with 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 [NY] Heart Association 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 panobinostat
  • Patients with diarrhea > Common Terminology Criteria for Adverse Events (CTCAE) grade 2
  • 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
  • Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
  • Known hypersensitivity to thalidomide or lenalidomide.
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Pregnant or breastfeeding females
  • Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis B or C; baseline testing for HIV and hepatitis C is not required. Patients who are seropositive because of hepatitis B virus vaccine are eligible.
  • Concurrent use of other anti-cancer agents or treatments
  • Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Lenalidomide and Panobinostat
In the phase I trial, three patients will be enrolled at each dose level, starting at dose level 1 using a standard 3 + 3 dose escalation phase I design.
Drug: panobinostat
Administered orally Monday, Wednesday, Friday of every week for 4 weeks. A cycle is define as 28 days.
Other Names:
  • LBH589
  • HDAC inhibitor
  • hydroxamic acid
Drug: lenalidomide
Lenalidomide will be administered orally daily on days 1-21. Lenalidomide will not be given on days 22-28. A cycle is define as 28 days.
Other Names:
  • CC-5013
  • Revlimid

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Determine the Overall Response Rate (ORR), Including Complete Responses (CR) and Partial Responses (PR)
Time Frame: up to 24 months
Overall response rate (CR + PR) will be determined using the International response criteria with combined panobinostat and lenalidomide in patients with relapsed or refractory Hodgkin's lymphoma.
up to 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Assess the Safety and Tolerability of Combined Lenalidomide and Panobinostat in Patients With Previously Treated Hodgkin's Lymphoma.
Time Frame: up to 24 months
Safety and tolerability will be assessed for patients using the NIH-NCI Common Terminology Criteria (CTCAE) version 4.0
up to 24 months
Progression-free Survival in Patients With Previously Treated Hodgkin's Lymphoma Receiving Combined Lenalidomide and Panobinostat
Time Frame: 3-5 years
Determined from the date of start of therapy to death from any cause or censored at the last date the patient is known to be alive
3-5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ohio State University Comprehensive Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novartis
Celgene

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kristie Blum, MD, Ohio State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 13, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 16, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 16, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 14, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 26, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 27, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 14, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 9, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • OSU-10049
  • NCI-2011-03323 (Registry Identifier: Clinical Trial Reporting Program (CTRP))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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