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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00742027




Registration number
NCT00742027
Ethics application status
Date submitted
25/08/2008
Date registered
27/08/2008
Date last updated
28/07/2021

Titles & IDs
Public title
Phase II Study of Oral Panobinostat in Adult Participants With Relapsed/Refractory Classical Hodgkin's Lymphoma
Scientific 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
Secondary ID [1] 0 0
2008-003016-35
Secondary ID [2] 0 0
CLBH589E2214
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Classical Hodgkin's Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Panobinostat

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).


Treatment: Drugs: Panobinostat
Panobinostat hard gelatin capsules.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
From the start of the treatment of last participant up to 32 weeks
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
From start of treatment until progression/recurrence or start of a new cancer therapy (up to approximately 5 years)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
From the start of treatment up to approximately 5 years
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
From the start of treatment up to approximately 5 years
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
From the start of treatment up to approximately 5 years
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline to date of death from any cause (up to approximately 5 years)
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Up to approximately 5 years
Secondary outcome [7] 0 0
Maximum Observed Concentration (Cmax) of Panobinostat
Timepoint [7] 0 0
Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose
Secondary outcome [8] 0 0
The Time to Reach Maximum Plasma Concentration (Tmax) of Panobinostat
Timepoint [8] 0 0
Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose
Secondary outcome [9] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to 28 Hours (AUC0-28) for Panobinostat
Timepoint [9] 0 0
Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose
Secondary outcome [10] 0 0
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-8) for Panobinostat
Timepoint [10] 0 0
Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose

Eligibility
Key inclusion criteria
1. Participant age is = 18 years.

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

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

4. 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.

5. 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.

6. 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.

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

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

9. Participant has the ability to swallow capsules or tablets.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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%.

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

13. 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).

14. Participant has unresolved diarrhea = grade 2.

15. 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.

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

17. 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.

18. 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.

19. 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):

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

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

22. Participant not at a participating center.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [2] 0 0
Novartis Investigative Site - Malvern
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3144 - Malvern
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
West Virginia
Country [11] 0 0
Belgium
State/province [11] 0 0
Bruxelles
Country [12] 0 0
Belgium
State/province [12] 0 0
Charleroi
Country [13] 0 0
Belgium
State/province [13] 0 0
Leuven
Country [14] 0 0
Brazil
State/province [14] 0 0
RJ
Country [15] 0 0
Brazil
State/province [15] 0 0
SP
Country [16] 0 0
France
State/province [16] 0 0
Dijon
Country [17] 0 0
France
State/province [17] 0 0
Lille Cedex
Country [18] 0 0
France
State/province [18] 0 0
Lyon Cedex
Country [19] 0 0
France
State/province [19] 0 0
Marseille
Country [20] 0 0
France
State/province [20] 0 0
Rennes
Country [21] 0 0
France
State/province [21] 0 0
Villejuif Cedex
Country [22] 0 0
Germany
State/province [22] 0 0
Dresden
Country [23] 0 0
Germany
State/province [23] 0 0
Göttingen
Country [24] 0 0
Germany
State/province [24] 0 0
Köln
Country [25] 0 0
Israel
State/province [25] 0 0
Be'er Sheva
Country [26] 0 0
Israel
State/province [26] 0 0
Jerusalem
Country [27] 0 0
Israel
State/province [27] 0 0
Ramat Gan
Country [28] 0 0
Italy
State/province [28] 0 0
BO
Country [29] 0 0
Italy
State/province [29] 0 0
MI
Country [30] 0 0
Italy
State/province [30] 0 0
TO
Country [31] 0 0
Italy
State/province [31] 0 0
UD
Country [32] 0 0
Malaysia
State/province [32] 0 0
Selangor
Country [33] 0 0
New Zealand
State/province [33] 0 0
Auckland
Country [34] 0 0
Singapore
State/province [34] 0 0
Singapore
Country [35] 0 0
Spain
State/province [35] 0 0
Cataluña
Country [36] 0 0
Spain
State/province [36] 0 0
Madrid
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Greater Manchester
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00742027
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications