A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin's Lymphoma
Condition: 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
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: panobinostat; lenalidomide
Intervention description: Administered orally Monday, Wednesday, Friday of every week for 4 weeks. A cycle is define as 28 days.; 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.
Intervention MeSH terms: Lenalidomide; Panobinostat; Histone Deacetylase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: refractory Hodgkin's lymphoma; panobinostat; lenalidomide

Summary:

      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
    

Eligibility 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 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