Trial record 1 of 1 for:    NCT01460940
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A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin's Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Ohio State University Comprehensive Cancer Center
Sponsor:
Collaborators:
Celgene Corporation
Novartis
Information provided by (Responsible Party):
Kristie Blum, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01460940
First received: October 14, 2011
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

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


Condition Intervention Phase
Adult Lymphocyte Depletion Hodgkin Lymphoma
Adult Lymphocyte Predominant Hodgkin Lymphoma
Adult Mixed Cellularity Hodgkin Lymphoma
Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma
Adult Nodular Sclerosis Hodgkin Lymphoma
Recurrent Adult Hodgkin Lymphoma
Drug: panobinostat
Drug: lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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. [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the safety and tolerability of combined lenalidomide and panobinostat in patients with previously treated Hodgkin's lymphoma. [ Time Frame: up to 24 months ] [ Designated as safety issue: Yes ]
  • Determine progression-free survival in patients with previously treated Hodgkin's lymphoma receiving combined lenalidomide and panobinostat [ Time Frame: 3-5 years ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 25
Study Start Date: October 2011
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • HDAC inhibitor
  • LBH589
  • 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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 formula
  • 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
  • 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
  • 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
  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: NCT01460940

Contacts
Contact: Ohio State University Comprehensive Cancer Center 1-800-293-5066 Jamesline@osumc.edu
Contact: Kristie Blum, MD 614-293-4590 Kristie.Blum@osumc.edu

Locations
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Nancy Bartlett, MD    314-362-5654    nbartlet@dom.wustl.edu   
Principal Investigator: Nancy Bartlett, MD         
United States, Ohio
The Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Kristie A Blum, M.D.    614-293-8508    kristie.blum@osumc.edu   
Principal Investigator: Kristie A Blum, M.D.         
Sub-Investigator: Robert Baiocchi, M.D., Ph.D.         
Sub-Investigator: Don Benson, M.D., Ph.D.         
Sub-Investigator: John Byrd, M.D.         
Sub-Investigator: Beth Christian, M.D.         
Sub-Investigator: Steven Devine, M.D.         
Sub-Investigator: Joseph Flynn, D.O., M.P.H.         
Sub-Investigator: Jeffrey Jones, M.D., M.P.H.         
Sub-Investigator: Pierluigi Porcu, M.D.         
Sponsors and Collaborators
Kristie Blum
Celgene Corporation
Novartis
Investigators
Principal Investigator: Kristie Blum, MD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Kristie Blum, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01460940     History of Changes
Other Study ID Numbers: OSU-10049, NCI-2011-03323
Study First Received: October 14, 2011
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:
refractory Hodgkin's lymphoma
panobinostat
lenalidomide

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Sclerosis
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Lenalidomide
Thalidomide
Panobinostat
Histone Deacetylase Inhibitors
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014