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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00742027
• Collaborator: (none)
• Enrollment: 129
• Locations: 46
• Arm: 1
• Actual Duration (Months): 58.8
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Classical Hodgkin's Lymphoma	Drug: Panobinostat	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Sep 16, 2008
• Actual Primary Completion Date: Aug 12, 2013
• Actual Study Completion Date: Aug 12, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panobinostat 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; Panobinostat hard gelatin capsules.; Other Names: LBH589 LBH

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria [From the start of the treatment of last participant up to 32 weeks]

   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.

Secondary Outcome Measures

1. 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)]

   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.

2. Time To Overall Disease Response in Responders [From the start of treatment up to approximately 5 years]

   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.

3. Duration of Overall Disease Response [From the start of treatment up to approximately 5 years]

   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.

4. Progression Free Survival (PFS) [From the start of treatment up to approximately 5 years]

   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.

5. The Overall Survival (OS) [Baseline to date of death from any cause (up to approximately 5 years)]

   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.

6. Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), And Deaths as a Measure of Safety and Tolerability of Panobinostat [Up to approximately 5 years]

   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.

7. Maximum Observed Concentration (Cmax) of Panobinostat [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 [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 [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 [Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Participant age is ≥ 18 years.

2. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤

4. Participant has a history of classical Hodgkin's Lymphoma (HL) (i.e. Nodular sclerosing, Mixed-cellularity, Lymphocyte-rich, Lymphocyte depleted).

5. 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).

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.

1. 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.

1. 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 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.

1. Clinically euthyroid. Note: Participants are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.

2. Written informed consent was obtained from the participant prior to any study-specific screening procedures.

3. Participant has the ability to swallow capsules or tablets.

Exclusion Criteria:

1. Participant has a history of prior treatment with a deacetylase (DAC) inhibitor including panobinostat.

2. Participant will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat treatment.

3. 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.

4. 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.

5. Participant has been treated with > 5 prior systemic lines of treatment (see Post-text supplement 2 for definitions and examples).

6. 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.

7. Participant is using any anti-cancer therapy concomitantly.

8. 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).

9. 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.

10. Participant has a history of central nervous system (CNS) involvement with lymphoma.

11. 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%.

1. Participant has any other clinically significant heart disease (e.g., uncontrolled hypertension).

2. 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).

3. Participant has unresolved diarrhea ≥ grade 2.

4. 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.

5. Participant has a known history of human immunodeficiency virus (HIV) seropositivity (screening HIV testing is not required).

6. 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.

7. 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.

8. 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):

1. Fasting blood glucose above 200 milligrams per deciliter (mg/dL), at time of PET scan.

2. Inability to lay down for 60 minutes or has a history of claustrophobia.

3. Participant not at a participating center.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center Dept.ofCityofHopeMedicalCtr(2)	Duarte	California	United States	91010-3000
2	Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)	Atlanta	Georgia	United States	30322
3	Georgia Regents University Cancer Clinical Research Unit	Augusta	Georgia	United States	30912
4	Rush University Medical Center Divisionof Hem/Onc Research(2)	Chicago	Illinois	United States	60612
5	VA Maryland Health Care Dept.of GreenbaumCancerCent(5)	Baltimore	Maryland	United States	21201
6	Dana Farber Cancer Institute Hematology / Oncology	Boston	Massachusetts	United States	02115
7	Karmanos Cancer Institute Div.of Hematology/Oncology	Detroit	Michigan	United States	48201
8	Mayo Clinic - Rochester Hematology	Rochester	Minnesota	United States	55905
9	University of Pennsylvania Medical Center Dept of UPenn Med Ctr (3)	Philadelphia	Pennsylvania	United States	19104-4283
10	University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(3)	Houston	Texas	United States	77030-4009
11	The Methodist Hospital Cell & Gene Therapy Clinic	Houston	Texas	United States	77030
12	Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(5)	San Antonio	Texas	United States	78229
13	West Virginia University/ Mary Babb Randolph Cancer Center	Morgantown	West Virginia	United States	26506
14	Novartis Investigative Site	Herston	Queensland	Australia	4029
15	Novartis Investigative Site	Malvern	Victoria	Australia	3144
16	Novartis Investigative Site	Bruxelles		Belgium	1000
17	Novartis Investigative Site	Charleroi		Belgium	6000
18	Novartis Investigative Site	Leuven		Belgium	3000
19	Novartis Investigative Site	Rio de Janeiro	RJ	Brazil	21941-913
20	Novartis Investigative Site	Campinas	SP	Brazil	13083-970
21	Novartis Investigative Site	São Paulo	SP	Brazil	01224-000
22	Novartis Investigative Site	São Paulo	SP	Brazil	05403-000
23	Novartis Investigative Site	Dijon		France	21034
24	Novartis Investigative Site	Lille Cedex		France	59 037
25	Novartis Investigative Site	Lyon Cedex		France	69373
26	Novartis Investigative Site	Marseille		France	13273
27	Novartis Investigative Site	Rennes		France	35019
28	Novartis Investigative Site	Villejuif Cedex		France	94805
29	Novartis Investigative Site	Dresden		Germany	01307
30	Novartis Investigative Site	Göttingen		Germany	37075
31	Novartis Investigative Site	Köln		Germany	50924
32	Novartis Investigative Site	Be'er Sheva		Israel	84101
33	Novartis Investigative Site	Jerusalem		Israel	91120
34	Novartis Investigative Site	Ramat Gan		Israel	52621
35	Novartis Investigative Site	Bologna	BO	Italy	40138
36	Novartis Investigative Site	Milano	MI	Italy	20162
37	Novartis Investigative Site	Rozzano	MI	Italy	20089
38	Novartis Investigative Site	Torino	TO	Italy	10126
39	Novartis Investigative Site	Udine	UD	Italy	33100
40	Novartis Investigative Site	Selangor		Malaysia	68000
41	Novartis Investigative Site	Auckland		New Zealand
42	Novartis Investigative Site	Singapore		Singapore	169608
43	Novartis Investigative Site	Barcelona	Cataluña	Spain	08025
44	Novartis Investigative Site	Madrid		Spain	28006
45	Novartis Investigative Site	Withington	Greater Manchester	United Kingdom	M20 4BX
46	Novartis Investigative Site	Southampton		United Kingdom

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00742027
• Other Study ID Numbers: CLBH589E2214; 2008-003016-35
• First Posted: Aug 27, 2008
• Last Update Posted: Jul 28, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: 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
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Panobinostat

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at 45 sites in 13 countries from 16 September 2008 to 12 August 2013.
Pre-assignment Detail	A total of 102 participants were to be enrolled and treated in the study. However, 129 participants got enrolled and analyzed, out of which no participant completed the study.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Period Title: Overall Study
STARTED	129
COMPLETED	0
NOT COMPLETED	129

Baseline Characteristics

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Overall Participants	129
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.7 (12.24)
Sex: Female, Male (Count of Participants)
Female	63 48.8%
Male	66 51.2%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria
Description	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.
Time Frame	From the start of the treatment of last participant up to 32 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all participants who received at least one dose of study drug.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Measure Participants	129
Complete Response	5 3.9%
Partial Response	30 23.3%
Stable Disease	71 55%
Progressive Disease	14 10.9%
Unknown	9 7%

2. Secondary Outcome

Title	Response Rate Based on Central Review of Computed Tomography (CT) Scan/Magnetic Resonance Imaging (MRI)
Description	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.
Time Frame	From start of treatment until progression/recurrence or start of a new cancer therapy (up to approximately 5 years)

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least one dose of study drug.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Measure Participants	129
Complete Response	0.8 0.6%
Partial Response	20.9 16.2%
Stable Disease	56.6 43.9%
Progressive Disease	15.5 12%
Unknown	6.2 4.8%

3. Secondary Outcome

Title	Time To Overall Disease Response in Responders
Description	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.
Time Frame	From the start of treatment up to approximately 5 years

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least one dose of study drug. Participants who were responders among those who were had relapsed/refractory classical Hodgkin's lymphoma were evaluated for this outcome measure. Time to overall disease response was calculated by Kaplan-Meier estimation.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Measure Participants	35
Median (95% Confidence Interval) [weeks]	9.9

4. Secondary Outcome

Title	Duration of Overall Disease Response
Description	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.
Time Frame	From the start of treatment up to approximately 5 years

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least one dose of study drug. Participants who were responders among those who were had relapsed/refractory classical Hodgkin's lymphoma were evaluated for this outcome measure. Time to overall disease response was calculated by Kaplan-Meier estimation.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Measure Participants	35
Median (95% Confidence Interval) [weeks]	30.1

5. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	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.
Time Frame	From the start of treatment up to approximately 5 years

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least one dose of study drug.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Measure Participants	129
Median (95% Confidence Interval) [months]	6.1

6. Secondary Outcome

Title	The Overall Survival (OS)
Description	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.
Time Frame	Baseline to date of death from any cause (up to approximately 5 years)

Outcome Measure Data

Analysis Population Description

FAS included all participants who received at least one dose of study drug.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Measure Participants	129
Median (Full Range) [months]	34.9

7. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), And Deaths as a Measure of Safety and Tolerability of Panobinostat
Description	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.
Time Frame	Up to approximately 5 years

Outcome Measure Data

Analysis Population Description

Safety set population included all participants who received at least one dose of study drug and had at least one valid post-baseline safety assessment.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Measure Participants	129
AEs	100 77.5%
SAEs	39.5 30.6%
Deaths	45.0 34.9%

8. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of Panobinostat
Time Frame	Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic set (PK) included all participants who have received at least one dose of panobinostat and had sufficient and evaluable blood samples for the Day 1 PK profile.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Measure Participants	13
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]	41.88 (22.165)

9. Secondary Outcome

Title	The Time to Reach Maximum Plasma Concentration (Tmax) of Panobinostat
Time Frame	Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose

Outcome Measure Data

Analysis Population Description

PK population included all participants who have received at least one dose of panobinostat and had sufficient and evaluable blood samples for the Day 1 PK profile.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Measure Participants	13
Median (Full Range) [hours]	1.1

10. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to 28 Hours (AUC0-28) for Panobinostat
Time Frame	Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose

Outcome Measure Data

Analysis Population Description

PK population included all participants who have received at least one dose of panobinostat and had sufficient and evaluable blood samples for the Day 1 PK profile.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Measure Participants	13
Mean (Standard Deviation) [hour*nanograms per milliliter (h.ng/mL)]	233.38 (112.138)

11. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-∞) for Panobinostat
Time Frame	Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose

Outcome Measure Data

Analysis Population Description

PK population included all participants who have received at least one dose of panobinostat and had sufficient and evaluable blood samples for the Day 1 PK profile. Overall number analyzed is the number of participants with data available for this analyses.

Arm/Group Title	Panobinostat
Arm/Group Description	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).
Measure Participants	11
Mean (Standard Deviation) [h.ng/mL]	239.36 (104.263)

Adverse Events

Time Frame	Up to approximately 5 years
Adverse Event Reporting Description	Safety set population included all participants who received at least one dose of study drug and had at least one valid post-baseline safety assessment.
Arm/Group Title	Panobinostat
Arm/Group Description	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).
All Cause Mortality
	Panobinostat
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Panobinostat
	Affected / at Risk (%)	# Events
Total	51/129 (39.5%)
Blood and lymphatic system disorders
Anaemia	5/129 (3.9%)
Febrile neutropenia	1/129 (0.8%)
Haemorrhagic disorder	1/129 (0.8%)
Idiopathic thrombocytopenic purpura	1/129 (0.8%)
Neutropenia	2/129 (1.6%)
Thrombocytopenia	12/129 (9.3%)
Cardiac disorders
Atrial fibrillation	3/129 (2.3%)
Pericardial effusion	1/129 (0.8%)
Sinus tachycardia	1/129 (0.8%)
Ventricular hypokinesia	1/129 (0.8%)
Gastrointestinal disorders
Abdominal pain	1/129 (0.8%)
Colitis	1/129 (0.8%)
Diarrhoea	2/129 (1.6%)
Gastritis	1/129 (0.8%)
Nausea	1/129 (0.8%)
Upper gastrointestinal haemorrhage	1/129 (0.8%)
Vomiting	2/129 (1.6%)
General disorders
Multi-organ failure	1/129 (0.8%)
Pyrexia	2/129 (1.6%)
Hepatobiliary disorders
Cholecystitis acute	1/129 (0.8%)
Cholelithiasis	1/129 (0.8%)
Infections and infestations
Appendicitis	1/129 (0.8%)
Bronchopneumonia	1/129 (0.8%)
Cellulitis	1/129 (0.8%)
Dengue fever	1/129 (0.8%)
Device related infection	2/129 (1.6%)
Device related sepsis	1/129 (0.8%)
Infection	1/129 (0.8%)
Lower respiratory tract infection	2/129 (1.6%)
Necrotising ulcerative gingivostomatitis	1/129 (0.8%)
Neutropenic sepsis	1/129 (0.8%)
Oropharyngeal candidiasis	1/129 (0.8%)
Pneumocystis jirovecii pneumonia	1/129 (0.8%)
Pneumonia	5/129 (3.9%)
Pneumonia pneumococcal	1/129 (0.8%)
Sepsis	4/129 (3.1%)
Septic shock	1/129 (0.8%)
Sinusitis	1/129 (0.8%)
Metabolism and nutrition disorders
Cachexia	1/129 (0.8%)
Decreased appetite	1/129 (0.8%)
Dehydration	2/129 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervicitis human papilloma virus	1/129 (0.8%)
Neoplasm skin	1/129 (0.8%)
Neuroendocrine carcinoma of the skin	1/129 (0.8%)
Nervous system disorders
Dizziness	1/129 (0.8%)
Headache	1/129 (0.8%)
Intracranial venous sinus thrombosis	1/129 (0.8%)
Lethargy	1/129 (0.8%)
Nerve root compression	1/129 (0.8%)
Neuralgia	1/129 (0.8%)
Peripheral nerve lesion	1/129 (0.8%)
Posterior reversible encephalopathy syndrome	1/129 (0.8%)
Syncope	1/129 (0.8%)
Psychiatric disorders
Confusional state	1/129 (0.8%)
Depression	1/129 (0.8%)
Mental status changes	1/129 (0.8%)
Renal and urinary disorders
Renal failure acute	1/129 (0.8%)
Urethral haemorrhage	1/129 (0.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/129 (3.1%)
Lung disorder	1/129 (0.8%)
Pleural effusion	1/129 (0.8%)
Pulmonary embolism	1/129 (0.8%)
Vascular disorders
Deep vein thrombosis	2/129 (1.6%)
Hypotension	3/129 (2.3%)
Other (Not Including Serious) Adverse Events
	Panobinostat
	Affected / at Risk (%)	# Events
Total	129/129 (100%)
Blood and lymphatic system disorders
Anaemia	52/129 (40.3%)
Leukopenia	16/129 (12.4%)
Lymphopenia	5/129 (3.9%)
Neutropenia	36/129 (27.9%)
Thrombocytopenia	109/129 (84.5%)
Cardiac disorders
Bradycardia	4/129 (3.1%)
Palpitations	4/129 (3.1%)
Sinus tachycardia	7/129 (5.4%)
Tachycardia	8/129 (6.2%)
Endocrine disorders
Hypothyroidism	20/129 (15.5%)
Gastrointestinal disorders
Abdominal distension	5/129 (3.9%)
Abdominal pain	17/129 (13.2%)
Abdominal pain lower	4/129 (3.1%)
Abdominal pain upper	21/129 (16.3%)
Aphthous stomatitis	3/129 (2.3%)
Constipation	25/129 (19.4%)
Diarrhoea	96/129 (74.4%)
Dry mouth	14/129 (10.9%)
Dyspepsia	12/129 (9.3%)
Flatulence	6/129 (4.7%)
Gastritis	4/129 (3.1%)
Gastrooesophageal reflux disease	3/129 (2.3%)
Gingival bleeding	5/129 (3.9%)
Haemorrhoids	3/129 (2.3%)
Nausea	87/129 (67.4%)
Stomatitis	9/129 (7%)
Vomiting	55/129 (42.6%)
General disorders
Asthenia	24/129 (18.6%)
Chills	8/129 (6.2%)
Fatigue	60/129 (46.5%)
Influenza like illness	4/129 (3.1%)
Local swelling	4/129 (3.1%)
Non-cardiac chest pain	10/129 (7.8%)
Oedema peripheral	17/129 (13.2%)
Pyrexia	56/129 (43.4%)
Thirst	3/129 (2.3%)
Hepatobiliary disorders
Hyperbilirubinaemia	5/129 (3.9%)
Infections and infestations
Bronchitis	4/129 (3.1%)
Bronchopneumonia	6/129 (4.7%)
Cystitis	3/129 (2.3%)
Device related infection	3/129 (2.3%)
Ear infection	3/129 (2.3%)
Folliculitis	4/129 (3.1%)
Herpes zoster	3/129 (2.3%)
Influenza	8/129 (6.2%)
Lower respiratory tract infection	7/129 (5.4%)
Lung infection	5/129 (3.9%)
Nail infection	3/129 (2.3%)
Nasopharyngitis	12/129 (9.3%)
Oral candidiasis	3/129 (2.3%)
Oral herpes	5/129 (3.9%)
Pneumonia	5/129 (3.9%)
Respiratory tract infection	5/129 (3.9%)
Rhinitis	4/129 (3.1%)
Sinusitis	9/129 (7%)
Upper respiratory tract infection	19/129 (14.7%)
Urinary tract infection	7/129 (5.4%)
Injury, poisoning and procedural complications
Contusion	7/129 (5.4%)
Investigations
Alanine aminotransferase increased	6/129 (4.7%)
Aspartate aminotransferase increased	6/129 (4.7%)
Blood alkaline phosphatase increased	7/129 (5.4%)
Blood creatine phosphokinase increased	3/129 (2.3%)
Blood creatinine increased	10/129 (7.8%)
Blood potassium decreased	4/129 (3.1%)
Blood thyroid stimulating hormone increased	3/129 (2.3%)
Electrocardiogram QT prolonged	4/129 (3.1%)
Electrocardiogram T wave inversion	3/129 (2.3%)
Gamma-glutamyltransferase increased	4/129 (3.1%)
Platelet count decreased	4/129 (3.1%)
Weight decreased	16/129 (12.4%)
Metabolism and nutrition disorders
Decreased appetite	48/129 (37.2%)
Dehydration	7/129 (5.4%)
Fluid retention	3/129 (2.3%)
Hyperglycaemia	3/129 (2.3%)
Hypoalbuminaemia	5/129 (3.9%)
Hypocalcaemia	6/129 (4.7%)
Hypokalaemia	19/129 (14.7%)
Hypomagnesaemia	7/129 (5.4%)
Hyponatraemia	4/129 (3.1%)
Hypophosphataemia	8/129 (6.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/129 (6.2%)
Back pain	24/129 (18.6%)
Bone pain	10/129 (7.8%)
Muscle spasms	30/129 (23.3%)
Musculoskeletal chest pain	13/129 (10.1%)
Musculoskeletal pain	4/129 (3.1%)
Myalgia	14/129 (10.9%)
Pain in extremity	7/129 (5.4%)
Nervous system disorders
Dizziness	8/129 (6.2%)
Dysgeusia	21/129 (16.3%)
Headache	27/129 (20.9%)
Lethargy	9/129 (7%)
Neuralgia	5/129 (3.9%)
Paraesthesia	3/129 (2.3%)
Sinus headache	4/129 (3.1%)
Somnolence	3/129 (2.3%)
Tremor	5/129 (3.9%)
Psychiatric disorders
Anxiety	16/129 (12.4%)
Confusional state	3/129 (2.3%)
Depression	11/129 (8.5%)
Insomnia	12/129 (9.3%)
Renal and urinary disorders
Dysuria	5/129 (3.9%)
Haematuria	4/129 (3.1%)
Reproductive system and breast disorders
Vaginal haemorrhage	4/129 (3.1%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	3/129 (2.3%)
Cough	36/129 (27.9%)
Dyspnoea	23/129 (17.8%)
Dyspnoea exertional	6/129 (4.7%)
Epistaxis	15/129 (11.6%)
Haemoptysis	3/129 (2.3%)
Oropharyngeal pain	10/129 (7.8%)
Pleural effusion	4/129 (3.1%)
Productive cough	10/129 (7.8%)
Rhinorrhoea	5/129 (3.9%)
Sinus congestion	4/129 (3.1%)
Wheezing	7/129 (5.4%)
Skin and subcutaneous tissue disorders
Alopecia	8/129 (6.2%)
Dry skin	13/129 (10.1%)
Erythema	3/129 (2.3%)
Hyperhidrosis	3/129 (2.3%)
Night sweats	4/129 (3.1%)
Petechiae	12/129 (9.3%)
Pruritus	21/129 (16.3%)
Rash	11/129 (8.5%)
Vascular disorders
Haematoma	5/129 (3.9%)
Hypotension	5/129 (3.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.