Phase II Study of Oral Panobinostat in Adult Participants With Relapsed/Refractory Classical Hodgkin's Lymphoma

NCT00742027 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CLBH589E22142008-003016-35
• Study Type: interventional
• Target: 129
• Locations: 13 countries
• Sites: 46

Brief Summary

This study evaluated the efficacy of oral panobinostat in participants with refractory/relapsed classical Hodgkins lymphoma (HL) who have received prior treatment with high dose chemotherapy and autologous stem cell transplant. Safety of panobinostat also was assessed. Other markers that may correlate with efficacy or safety were explored.

Conditions

Classical Hodgkin's Lymphoma

Keywords

Classical Hodgkin Lymphoma; Classical Hodgkin's Lymphoma; Hodgkin Lymphoma; Hodgkin's Lymphoma; Nodular sclerosing; Mixed-cellularity; Lymphocyte-rich; Lymphocyte depleted; HL; Classical HL; Refractory Hodgkin's Lymphoma; Refractory Hodgkin Lymphoma; Refractory HL

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria

  ORR was number of participants with best overall disease response of complete response(CR)/partial response(PR).Best overall disease response was best disease response recorded from start of treatment until disease progression/recurrence.CR=complete normalization of all index nodal,extranodal lesions,complete disappearance of all extranodal lesions.PR=50% decrease in SPD for up to 6 identified dominant lesions (splenic,hepatic nodules) from baseline.Stable=neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease (PD), reference smallest sum diameters while on study.Progression=50% increase in sum of longest diameter of all target lesions,from smallest sum of longest diameter of all target lesions recorded at or after baseline/a new lesion/progression of non-target lesions.Unknown is progression not documented,one/more of index lesions not assessed or have been assessed using a different method than baseline at the time of radiologic evaluation.

  From the start of the treatment of last participant up to 32 weeks

Secondary Outcomes (10)

• Response Rate Based on Central Review of Computed Tomography (CT) Scan/Magnetic Resonance Imaging (MRI)

  From start of treatment until progression/recurrence or start of a new cancer therapy (up to approximately 5 years)

• Time To Overall Disease Response in Responders

  From the start of treatment up to approximately 5 years

• Duration of Overall Disease Response

  From the start of treatment up to approximately 5 years

• Progression Free Survival (PFS)

  From the start of treatment up to approximately 5 years

• The Overall Survival (OS)

  Baseline to date of death from any cause (up to approximately 5 years)

Study Arms (1)

Panobinostat

EXPERIMENTAL

Participants received panobinostat 40 mg, capsules, orally, thrice every week (i.e. days 1, 3 and 5), in each cycle of 21 days until unacceptable toxicity, disease progression, start of new anti-cancer therapy or withdrawal of consent (up to approximately 48 months).

Drug: Panobinostat

Interventions

Panobinostat DRUG

Panobinostat hard gelatin capsules.

Also known as: LBH589, LBH

Panobinostat

Eligibility Criteria

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

You may qualify if:

• Participant age is ≥ 18 years.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Participant has a history of classical Hodgkin's Lymphoma (HL) (i.e. Nodular sclerosing, Mixed-cellularity, Lymphocyte-rich, Lymphocyte depleted).
• Participant has progressive disease after receiving high dose chemotherapy with autologous hematopoietic stem cell transplant (AHSCT).
• Note: If last therapy was ≥ 18 months ago, then biopsy should be performed to confirm diagnosis.
• Note: Participant should have received ≤ 5 prior systemic treatment regimens (See Post-text supplement 2 for definitions and examples).
• Participant has at least one site of measurable nodal disease at baseline ≥ 2.0 centimeter (cm) in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by computed tomography (CT) scan (magnetic resonance imaging \[MRI\] is allowed only if CT scan can not be performed).
• Note: Participant with bone marrow involvement are eligible, but this criteria alone should not be used for disease measurement.
• Participant has the following laboratory values (labs may be repeated, if needed, to obtain acceptable values before screen fail):
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/liter (L) \[International System of Units {SI} units 1.5 x 10\^9/L\].
• Platelet count ≥ 75 x 10\^9/L.
• Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution.
• Note: Potassium, calcium, magnesium, sodium, and/or phosphorus supplements may be given to correct values that are \< lower limits of normal (LLN). Post-correction values must not be deemed to be a clinically significant abnormality prior to participant being dosed.
• Serum creatinine ≤ 1.5 x upper limits of normal (ULN).
• Serum bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN, if participant has Gilbert syndrome).

You may not qualify if:

• Participant has a history of prior treatment with a deacetylase (DAC) inhibitor including panobinostat.
• Participant will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat treatment.
• Participant has been treated with monoclonal antibody therapy (e.g., rituximab or anti CD-30 antibody, etc.) within 4 weeks of start of study treatment.
• Participant has received chemotherapy or any investigational drug or undergone major surgery ≤ 2 weeks prior to starting study drug or whose side effects of such therapy have not resolved to ≤ grade 1.
• Participant has been treated with \> 5 prior systemic lines of treatment (see Post-text supplement 2 for definitions and examples).
• Participant has received prior radiation therapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to start of study treatment or whose side effects of such therapy have not resolved to ≤ grade 1.
• Participant is using any anti-cancer therapy concomitantly.
• Participant treated with allogeneic hematopoietic stem cell transplant who is currently on or has received immunosuppressive therapy within 90 days prior to start of screening and/or have ≥ Grade 2 graft versus host disease (GvHD).
• Participant has a history of another primary malignancy ≤ 3 years before study entry, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix.
• Participant has a history of central nervous system (CNS) involvement with lymphoma.
• Participant has impaired cardiac function including any of the following:
• Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (\<50 beats per minute \[bpm\]), QT interval (QTcF) \> 450 milliseconds (msec) on screening electrocardiography (ECG), or right bundle branch block + left anterior hemiblock (bifascicular block).
• Presence of atrial fibrillation (ventricular heart rate \>100 bpm).
• Previous history angina pectoris or acute myocardial infarction (MI) within 6 months.
• Congestive heart failure (New York Heart Association functional classification III-IV) or baseline multigated acquisition (MUGA)/Echo shows left ventricular ejection fraction (LVEF) \< 45%.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (46)

City of Hope National Medical Center Dept.ofCityofHopeMedicalCtr(2)

Duarte, California, 91010-3000, United States

Location

Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)

Atlanta, Georgia, 30322, United States

Location

Georgia Regents University Cancer Clinical Research Unit

Augusta, Georgia, 30912, United States

Location

Rush University Medical Center Divisionof Hem/Onc Research(2)

Chicago, Illinois, 60612, United States

Location

VA Maryland Health Care Dept.of GreenbaumCancerCent(5)

Baltimore, Maryland, 21201, United States

Location

Dana Farber Cancer Institute Hematology / Oncology

Boston, Massachusetts, 02115, United States

Location

Karmanos Cancer Institute Div.of Hematology/Oncology

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - Rochester Hematology

Rochester, Minnesota, 55905, United States

Location

University of Pennsylvania Medical Center Dept of UPenn Med Ctr (3)

Philadelphia, Pennsylvania, 19104-4283, United States

Location

University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(3)

Houston, Texas, 77030-4009, United States

Location

The Methodist Hospital Cell & Gene Therapy Clinic

Houston, Texas, 77030, United States

Location

Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(5)

San Antonio, Texas, 78229, United States

Location

West Virginia University/ Mary Babb Randolph Cancer Center

Morgantown, West Virginia, 26506, United States

Location

Novartis Investigative Site

Herston, Queensland, 4029, Australia

Location

Novartis Investigative Site

Malvern, Victoria, 3144, Australia

Location

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Charleroi, 6000, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 21941-913, Brazil

Location

Novartis Investigative Site

Campinas, São Paulo, 13083-970, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01224-000, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403-000, Brazil

Location

Novartis Investigative Site

Dijon, 21034, France

Location

Novartis Investigative Site

Lille, 59 037, France

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Marseille, 13273, France

Location

Novartis Investigative Site

Rennes, 35019, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Cologne, 50924, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Göttingen, 37075, Germany

Location

Novartis Investigative Site

Beersheba, 84101, Israel

Location

Novartis Investigative Site

Jerusalem, 91120, Israel

Location

Novartis Investigative Site

Ramat Gan, 52621, Israel

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Udine, UD, 33100, Italy

Location

Novartis Investigative Site

Kuala Selangor, 68000, Malaysia

Location

Novartis Investigative Site

Auckland, New Zealand

Location

Novartis Investigative Site

Singapore, 169608, Singapore

Location

Novartis Investigative Site

Barcelona, Catalonia, 08025, Spain

Location

Novartis Investigative Site

Madrid, 28006, Spain

Location

Novartis Investigative Site

Withington, Greater Manchester, M20 4BX, United Kingdom

Location

Novartis Investigative Site

Southampton, United Kingdom

Location

Related Publications (2)

• Chari A, Cho HJ, Dhadwal A, Morgan G, La L, Zarychta K, Catamero D, Florendo E, Stevens N, Verina D, Chan E, Leshchenko V, Lagana A, Perumal D, Mei AH, Tung K, Fukui J, Jagannath S, Parekh S. A phase 2 study of panobinostat with lenalidomide and weekly dexamethasone in myeloma. Blood Adv. 2017 Aug 21;1(19):1575-1583. doi: 10.1182/bloodadvances.2017007427. eCollection 2017 Aug 22.

  PMID: 29296798 DERIVED

• Harrison SJ, Hsu AK, Neeson P, Younes A, Sureda A, Engert A, Prince HM, Li M, Savage P, Bugarini R, Williams D, Squier M, Ritchie DS. Early thymus and activation-regulated chemokine (TARC) reduction and response following panobinostat treatment in patients with relapsed/refractory Hodgkin lymphoma following autologous stem cell transplant. Leuk Lymphoma. 2014 May;55(5):1053-60. doi: 10.3109/10428194.2013.820287. Epub 2013 Aug 5.

  PMID: 23822537 DERIVED

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Panobinostat

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)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 25, 2008
• First Posted: August 27, 2008
• Study Start: September 16, 2008
• Primary Completion: August 12, 2013
• Study Completion: August 12, 2013
• Last Updated: July 28, 2021
• Results First Posted: June 3, 2021

Record last verified: 2021-07

Locations

ES (2); BR (4); US (13); FR (6); IT (5); BE (3); DE (3); SG (1); GB (2); AU (2); IL (3); MY (1); NZ (1)