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

NCT01460940 | Completed Phase 2 Results DMC

• 2 other identifiers: OSU-10049NCI-2011-03323
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief 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

Conditions

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

Keywords

refractory Hodgkin's lymphoma; panobinostat; lenalidomide

Outcome Measures

Primary Outcomes (1)

• Determine the Overall Response Rate (ORR), Including Complete Responses (CR) and Partial Responses (PR)

  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 Outcomes (2)

• Assess the Safety and Tolerability of Combined Lenalidomide and Panobinostat in Patients With Previously Treated Hodgkin's Lymphoma.

  up to 24 months

• Progression-free Survival in Patients With Previously Treated Hodgkin's Lymphoma Receiving Combined Lenalidomide and Panobinostat

  3-5 years

Study Arms (1)

Lenalidomide and Panobinostat

EXPERIMENTAL

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; Drug: lenalidomide

Interventions

panobinostat DRUG

Administered orally Monday, Wednesday, Friday of every week for 4 weeks. A cycle is define as 28 days.

Also known as: HDAC inhibitor, LBH589, hydroxamic acid

Lenalidomide and Panobinostat

lenalidomide DRUG

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.

Also known as: CC-5013, Revlimid

Lenalidomide and Panobinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• Celgene: collaborator
• Novartis: collaborator

Study Sites (2)

Washington University

St Louis, Missouri, 63110, United States

Location

The Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Maly JJ, Christian BA, Zhu X, Wei L, Sexton JL, Jaglowski SM, Devine SM, Fehniger TA, Wagner-Johnston ND, Phelps MA, Bartlett NL, Blum KA. A Phase I/II Trial of Panobinostat in Combination With Lenalidomide in Patients With Relapsed or Refractory Hodgkin Lymphoma. Clin Lymphoma Myeloma Leuk. 2017 Jun;17(6):347-353. doi: 10.1016/j.clml.2017.05.008. Epub 2017 May 22.

  PMID: 28622959 DERIVED

Related Links

• Jamesline

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Panobinostat; Histone Deacetylase Inhibitors; Hydroxamic Acids; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles

Results Point of Contact

• Title: Dr. Kristie Blum
• Organization: The Ohio State University Comprehensive Cancer Center

Kristie.Blum@osumc.edu

614-293-4590

Study Officials

• Kristie Blum, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: October 14, 2011
• First Posted: October 27, 2011
• Study Start: October 13, 2011
• Primary Completion: November 16, 2016
• Study Completion: November 16, 2016
• Last Updated: November 14, 2017
• Results First Posted: March 14, 2017

Record last verified: 2017-11

Locations

US (2)