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Classical Hodgkin's LymphomaPhase 2NCT00742027

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

A Phase 2 study testing Panobinostat in people with Classical Hodgkin's Lymphoma, run by Novartis Pharmaceuticals at 46 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Classical Hodgkin's Lymphoma
What is being tested?
Panobinostat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
129 participants
Where
46 sitesin 13 countries
Study dates
16 Sep 2008to 12 Aug 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • Note: Participant will be allowed on study who have also received an allogeneic hematopoietic stem cell transplant, however this therapy alone is not sufficient for inclusion into this study.
  • 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).
  • Aspartate transaminase (AST)/ serum glutamic oxaloacetic transaminase (SGOT) and/or alanine transaminase (ALT)/ serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x ULN or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement.
  • Clinically euthyroid. Note: Participants are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
  • Written informed consent was obtained from the participant prior to any study-specific screening procedures.
  • Participant has the ability to swallow capsules or tablets.

Who cannot join

  • 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.
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  • 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%.
  • Participant has any other clinically significant heart disease (e.g., uncontrolled hypertension).
  • Participant has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection).
  • Participant has unresolved diarrhea ≥ grade 2.
  • Participant has any other concurrent severe and/or uncontrolled medical condition(s) (e.g., uncontrolled diabetes mellitus, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol.
  • Participant has a known history of human immunodeficiency virus (HIV) seropositivity (screening HIV testing is not required).
  • Participant is using medications that have a relative risk of prolonging the QT interval or of inducing Torsade de Pointes, where such treatment cannot be discontinued or switched to a different medication prior to starting study drug.
  • Participant is a woman who is pregnant or breast feeding, or a women of childbearing potential (WOCBP) not willing to use a double method of contraception during the study through 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). WOCBP must have a negative serum pregnancy test at baseline.
  • Male participant whose sexual partner(s) are WOCBP who are not willing to use a double method of contraception, one of which includes a condom, during the study and for 3 months after the end of treatment.
  • Participants with any of the following contraindications to positron emission tomography (PET) are excluded from the [18F]- fludeoxyglucose (FDG) PET study (only applicable for centers participating in the PET study):
  • Fasting blood glucose above 200 milligrams per deciliter (mg/dL), at time of PET scan.
  • Inability to lay down for 60 minutes or has a history of claustrophobia.
  • Participant not at a participating center.

Trial locations and contacts

46 sites in 13 countries.

46 sites in 13 countries

United States13 sites

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

    Atlanta, Georgia, 30322

  • Georgia Regents University Cancer Clinical Research Unit

    Augusta, Georgia, 30912

  • VA Maryland Health Care Dept.of GreenbaumCancerCent(5)

    Baltimore, Maryland, 21201

  • Dana Farber Cancer Institute Hematology / Oncology

    Boston, Massachusetts, 02115

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

    Chicago, Illinois, 60612

  • Karmanos Cancer Institute Div.of Hematology/Oncology

    Detroit, Michigan, 48201

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

    Duarte, California, 91010-3000

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

    Houston, Texas, 77030-4009

  • The Methodist Hospital Cell & Gene Therapy Clinic

    Houston, Texas, 77030

  • West Virginia University/ Mary Babb Randolph Cancer Center

    Morgantown, West Virginia, 26506

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

    Philadelphia, Pennsylvania, 19104-4283

  • Mayo Clinic - Rochester Hematology

    Rochester, Minnesota, 55905

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

    San Antonio, Texas, 78229

Other trials in United States

France6 sites

  • Novartis Investigative Site

    Dijon, 21034

  • Novartis Investigative Site

    Lille, 59 037

  • Novartis Investigative Site

    Lyon, 69373

  • Novartis Investigative Site

    Marseille, 13273

  • Novartis Investigative Site

    Rennes, 35019

  • Novartis Investigative Site

    Villejuif, 94805

Other trials in France

Italy5 sites

  • Novartis Investigative Site

    Bologna, BO, 40138

  • Novartis Investigative Site

    Milan, MI, 20162

  • Novartis Investigative Site

    Rozzano, MI, 20089

  • Novartis Investigative Site

    Torino, TO, 10126

  • Novartis Investigative Site

    Udine, UD, 33100

Other trials in Italy

Brazil4 sites

  • Novartis Investigative Site

    Campinas, São Paulo, 13083-970

  • Novartis Investigative Site

    Rio de Janeiro, Rio de Janeiro, 21941-913

  • Novartis Investigative Site

    São Paulo, São Paulo, 01224-000

  • Novartis Investigative Site

    São Paulo, São Paulo, 05403-000

Other trials in Brazil

Belgium3 sites

  • Novartis Investigative Site

    Brussels, 1000

  • Novartis Investigative Site

    Charleroi, 6000

  • Novartis Investigative Site

    Leuven, 3000

Other trials in Belgium

Germany3 sites

  • Novartis Investigative Site

    Cologne, 50924

  • Novartis Investigative Site

    Dresden, 01307

  • Novartis Investigative Site

    Göttingen, 37075

Other trials in Germany

Israel3 sites

  • Novartis Investigative Site

    Beersheba, 84101

  • Novartis Investigative Site

    Jerusalem, 91120

  • Novartis Investigative Site

    Ramat Gan, 52621

Other trials in Israel

Australia2 sites

  • Novartis Investigative Site

    Herston, Queensland, 4029

  • Novartis Investigative Site

    Malvern, Victoria, 3144

Other trials in Australia

Spain2 sites

  • Novartis Investigative Site

    Barcelona, Catalonia, 08025

  • Novartis Investigative Site

    Madrid, 28006

Other trials in Spain

United Kingdom2 sites

  • Novartis Investigative Site

    Southampton

  • Novartis Investigative Site

    Withington, Greater Manchester, M20 4BX

Other trials in United Kingdom

Malaysia1 site

  • Novartis Investigative Site

    Kuala Selangor, 68000

Other trials in Malaysia

New Zealand1 site

  • Novartis Investigative Site

    Auckland

Other trials in New Zealand

Singapore1 site

  • Novartis Investigative Site

    Singapore, 169608

Other trials in Singapore

About this study

Official title: A Phase II Study of Oral Panobinostat in Adult Patients With Relapsed/Refractory Classical Hodgkins Lymphoma After High-dose Chemotherapy With Autologous Stem Cell Transplant

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.

Being tested
Panobinostat
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
Medical subject headings
Hodgkin Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PanobinostatDrug

    Also called LBH589, LBH

    Panobinostat hard gelatin capsules.

Study groups in NCT00742027
Study groupRoleWhat they receive
PanobinostatExperimentalParticipants 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).
Receives: Drug: Panobinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (10)

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

    Best overall radiological response (CT/MRI) was recorded from start of treatment until 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.

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

  2. Time To Overall Disease Response in Responders

    Time to overall disease response (CR or PR) was defined as the time from the date of randomization/start of treatment to the date of first documented disease response (PR or CR). Per Cheson response criteria, CR= is a complete normalization of all index nodal and extranodal lesions and complete disappearance of all extranodal lesions. PR= is a 50% decrease in the SPD for up to 6 identified dominant lesions, including splenic and hepatic nodules from baseline. Participants were considered responders if they had a partial or complete response to a treatment while in the study as per Investigator's assessment.

    Measured: From the start of treatment up to approximately 5 years

  3. Duration of Overall Disease Response

    Duration of overall response (CR or PR) was defined as the time from the date of first documented disease response (CR or PR) to the date of first documented progression or death due to lymphoma. Per Cheson response criteria, CR= is a complete normalization of all index nodal and extranodal lesions and complete disappearance of all extranodal lesions. PR= is a 50% decrease in the SPD for up to 6 identified dominant lesions, including splenic and hepatic nodules from baseline. Participants were considered responders if they had a partial or complete response to a treatment while in the study.

    Measured: From the start of treatment up to approximately 5 years

  4. Progression Free Survival (PFS)

    Progression-free survival (PFS) was defined as the time from the date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a participant has not had an event, progression-free survival was censored at the date of the last adequate assessment.

    Measured: From the start of treatment up to approximately 5 years

  5. The Overall Survival (OS)

    OS was the duration from date of randomization to date of death from any cause. If a participant has not had an event, overall survival was censored at the date of the last adequate assessment.

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

  6. Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), And Deaths as a Measure of Safety and Tolerability of Panobinostat

    An AE is the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) occurring after signing the informed consent even if the event is not considered to be related to the study drug(s). SAEs are AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.

    Measured: Up to approximately 5 years

  7. Maximum Observed Concentration (Cmax) of Panobinostat

    Measured: Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose

  8. The Time to Reach Maximum Plasma Concentration (Tmax) of Panobinostat

    Measured: Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose

  9. Area Under the Plasma Concentration-Time Curve From Time Zero to 28 Hours (AUC0-28) for Panobinostat

    Measured: Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose

  10. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-∞) for Panobinostat

    Measured: Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Aug 2008 (estimated)
  2. Study start16 Sep 2008
  3. Primary completion12 Aug 2013
  4. Study completion12 Aug 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
129 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00742027
Sponsor's protocol ID
CLBH589E2214
Other IDs
2008-003016-35, 2008
Status last verified
Jul 2021
First submitted
25 Aug 2008
Last updated
28 Jul 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 29296798

  • 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.

    PubMed 23822537

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Panobinostat in people with Classical Hodgkin's Lymphoma, run by Novartis Pharmaceuticals at 46 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in United States, France, Italy, Brazil, Belgium and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria (time frame: From the start of the treatment of last participant up to 32 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00742027, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2021.

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