PATH: A Phase III Randomized, Double Blind, Placebo Controlled Multi-center Study of Panobinostat for Maintenance of Response in Patients With Hodgkin's Lymphoma (HL)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01034163
• Collaborator: (none)
• Enrollment: 41
• Locations: 35
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective was to provide drug to ongoing patients who were receiving panobinostat and to characterize the safety and tolerability of panobinostat in patients with HL after achieving a complete response following autologous hematopoietic stem cell transplant (AHSCT) with high dose chemotherapy (HDT). Primary objective as stated above reflects a change from the original protocol as of an amendment. The original objective was no longer feasible with only 41 of 367 patients randomized after the study was halted due to poor recruitment. An amendment was written to allow patients on panobinostat to continue their treatment until discontinuation/completion criteria were met (patients were unblinded). Therefore, the study was completed as per this amendment. No secondary objectives were included for this trial from the amendment; this was a change from the original protocol.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin's Lymphoma	Drug: Panobinostat; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized, Double Blind, Placebo Controlled Multi-center Study of Panobinostat for Maintenance of Response in Patients With Hodgkin's Lymphoma Who Are at Risk for Relapse After High Dose Chemotherapy and Autologous Stem Cell Transplant (ASCT)
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panobinostat (PAN) Participants received 45 mg orally 3 times a week (TIW), every other week (QOW),	Drug: Panobinostat; Other Names: LBH589
Placebo Comparator: Placebo Participants received matching placebo to PAN TIW, QOW.	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [23 months]

   Safety monitoring was conducted throughout the study.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patient age is greater than or equal to 18 years

2. Patient has a history of histologically confirmed classical HL (i.e. Nodular sclerosing (NSHL), Mixed-cellularity (MCHL), Lymphocyte-rich (LRHL), Lymphocyte depleted (LDHL))

3. Patient has achieved a complete response by CT/MRI scan within 9 weeks (± 1 week) from the day of their first autologous peripheral blood/ bone marrow stem cell transfusion (AHSCT) following HDT. Complete response is defined as:

Normalization of all nodes and lesions compared to pre-transplant scan performed prior to salvage therapy for relapse. Any residual abnormal masses on the post transplant CT/MRI must be metabolically inactive on a PET scan.

1. Patient has at least one of the following factors that places them at risk for relapse:

• Primary refractory disease (including relapse in ≤ 3 months of completion of 1st line treatment)

• First relapse >3 but <12 months from last dose of 1st line treatment

• Multiple relapses (prior to transplant)

• Stage III/IV disease (at relapse, prior to transplant)

• Hemoglobin <10.5 gm/dL (at relapse, prior to transplant)

Exclusion Criteria:

Patient has been treated with allogeneic transplant 2. Patient has received any anti-lymphoma therapy after AHSCT including but not limited to:

• chemotherapy prior to start of study

• biologic immunotherapy including monoclonal antibodies or experimental therapy prior to start of study

• radiation therapy 3. Patient has not recovered from reversible toxicity due to any prior therapies (e.g. returned to baseline or Grade ≤1) except for hematological laboratory parameters Note: Patient does not meet this criteria if the toxicity is stable and irreversible, and there is no evidence that panobinostat causes a similar toxicity 4. Patient has received prior treatment with DAC inhibitors including panobinostat

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
2	University of California at Los Angeles	Los Angeles	California	United States	90095
3	Georgia Health Sciences University Medical College of Georgia	Augusta	Georgia	United States	30912
4	Northwestern University Oncology	Chicago	Illinois	United States	60611-3308
5	Indiana University	Indianapolis	Indiana	United States	46202
6	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
7	Dana-Farber Cancer Institute Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
8	Mayo Clinic - Rochester Hematology/Oncology Dept.	Rochester	Minnesota	United States	55905
9	Duke University Medical Center	Durham	North Carolina	United States	27710
10	Medical University of South Carolina Oncology	Charleston	South Carolina	United States	29425
11	Vanderbilt University Medical Center Vanderbilt Clinic - Oncology	Nashville	Tennessee	United States	37232
12	Mary Babb Randolph Cancer Center	Morgantown	West Virginia	United States	26506-9162
13	Medical College of Wisconsin Oncology	Milwaukee	Wisconsin	United States	53226
14	Novartis Investigative Site	Parkville	Victoria	Australia	3050
15	Novartis Investigative Site	Leuven		Belgium	3000
16	Novartis Investigative Site	Curitiba	PR	Brazil	81520-060
17	Novartis Investigative Site	Rio de Janeiro	RJ	Brazil	20230-130
18	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
19	Novartis Investigative Site	Caen	Cedex	France	14033
20	Novartis Investigative Site	Dijon		France	21079
21	Novartis Investigative Site	Lille Cedex		France	59 037
22	Novartis Investigative Site	Duisburg		Germany	47166
23	Novartis Investigative Site	Essen-Werden		Germany	45239
24	Novartis Investigative Site	Koeln		Germany	50937
25	Novartis Investigative Site	Haifa		Israel	3525408
26	Novartis Investigative Site	Ramat Gan		Israel	5266202
27	Novartis Investigative Site	Reggio Calabria	RC	Italy	89124
28	Novartis Investigative Site	Amsterdam		Netherlands
29	Novartis Investigative Site	Rotterdam		Netherlands	3075 EA
30	Novartis Investigative Site	Christchurch		New Zealand	8011
31	Novartis Investigative Site	Krakow		Poland	30-510
32	Novartis Investigative Site	Wroclaw		Poland	50-367
33	Novartis Investigative Site	ChelyabinskChemo		Russian Federation	620102
34	Novartis Investigative Site	Saint Petersburg		Russian Federation	197022
35	Novartis Investigative Site	Singapore		Singapore	119228

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: NCT01034163
• Other Study ID Numbers: CLBH589E2301; 2009-014846-26
• First Posted: Dec 17, 2009
• Last Update Posted: Jul 7, 2016
• Last Verified: May 1, 2016

• Keywords provided by Novartis Pharmaceuticals: Phase III randomized; double blind; placebo controlled multi-center study; panobinostat; Hodgkin's lymphoma; at risk for relapse; autologous stem cell transplant
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Panobinostat

Study Results

Participant Flow

Recruitment Details	Participants were randomized in a 2:1 ratio to the PAN and placebo groups, respectively.

Arm/Group Title	Panobinostat (PAN)	Placebo
Arm/Group Description	Participants received 45 mg orally 3 times a week (TIW), every other week (QOW).	Participants received matching placebo to PAN TIW, QOW.
Period Title: Overall Study
STARTED	27	14
Untreated (Not in Safety Set)	1	2
Safety Set	26	12
In Open Label Phase After Unblinding	5	0
COMPLETED	0	0
NOT COMPLETED	27	14

Baseline Characteristics

Arm/Group Title	Panobinostat (PAN)	Placebo	Total
Arm/Group Description	Participants received 45 mg orally 3 times a week (TIW), every other week (QOW).	Participants received matching placebo to PAN TIW, QOW.	Total of all reporting groups
Overall Participants	27	14	41
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34.0 (10.72)	30.6 (10.56)	32.9 (10.66)
Sex: Female, Male (Count of Participants)
Female	8 29.6%	7 50%	15 36.6%
Male	19 70.4%	7 50%	26 63.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Description	Safety monitoring was conducted throughout the study.
Time Frame	23 months

Outcome Measure Data

Analysis Population Description

Safety set: The safety set included randomized participants who received at least one dose of study treatment.

Arm/Group Title	Panobinostat (PAN)	Placebo
Arm/Group Description	Participants received 45 mg orally 3 times a week (TIW), every other week (QOW).	Participants received matching placebo to PAN TIW, QOW.
Measure Participants	26	12
Number [Participants]	26 96.3%	11 78.6%

Adverse Events

Arm/Group Title	Panobinostat (PAN)		Placebo
Arm/Group Description	Participants received 45 mg orally 3 times a week (TIW), every other week (QOW).		Participants received matching placebo to PAN TIW, QOW.
All Cause Mortality
	Panobinostat (PAN)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Panobinostat (PAN)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/26 (7.7%)		1/12 (8.3%)
General disorders
Pyrexia	1/26 (3.8%)		0/12 (0%)
Infections and infestations
Cellulitis	1/26 (3.8%)		0/12 (0%)
Gastroenteritis salmonella	1/26 (3.8%)		0/12 (0%)
Herpes zoster	0/26 (0%)		1/12 (8.3%)
Sinusitis bacterial	1/26 (3.8%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Panobinostat (PAN)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		11/12 (91.7%)
Blood and lymphatic system disorders
Anaemia	0/26 (0%)		1/12 (8.3%)
Leukopenia	3/26 (11.5%)		2/12 (16.7%)
Neutropenia	7/26 (26.9%)		4/12 (33.3%)
Thrombocytopenia	7/26 (26.9%)		1/12 (8.3%)
Gastrointestinal disorders
Abdominal pain	1/26 (3.8%)		2/12 (16.7%)
Abdominal pain upper	2/26 (7.7%)		0/12 (0%)
Constipation	2/26 (7.7%)		0/12 (0%)
Diarrhoea	23/26 (88.5%)		3/12 (25%)
Gastrooesophageal reflux disease	3/26 (11.5%)		0/12 (0%)
Nausea	15/26 (57.7%)		1/12 (8.3%)
Toothache	0/26 (0%)		1/12 (8.3%)
Vomiting	12/26 (46.2%)		3/12 (25%)
General disorders
Asthenia	3/26 (11.5%)		1/12 (8.3%)
Chills	1/26 (3.8%)		1/12 (8.3%)
Fatigue	9/26 (34.6%)		3/12 (25%)
Influenza like illness	4/26 (15.4%)		0/12 (0%)
Mucosal dryness	2/26 (7.7%)		0/12 (0%)
Non-cardiac chest pain	1/26 (3.8%)		1/12 (8.3%)
Pyrexia	4/26 (15.4%)		1/12 (8.3%)
Swelling	0/26 (0%)		1/12 (8.3%)
Infections and infestations
Herpes ophthalmic	0/26 (0%)		1/12 (8.3%)
Herpes virus infection	2/26 (7.7%)		1/12 (8.3%)
Herpes zoster	0/26 (0%)		2/12 (16.7%)
Influenza	0/26 (0%)		1/12 (8.3%)
Nasopharyngitis	5/26 (19.2%)		0/12 (0%)
Oral infection	0/26 (0%)		1/12 (8.3%)
Pharyngitis	0/26 (0%)		1/12 (8.3%)
Sinusitis	4/26 (15.4%)		1/12 (8.3%)
Upper respiratory tract infection	5/26 (19.2%)		1/12 (8.3%)
Urinary tract infection	2/26 (7.7%)		0/12 (0%)
Investigations
Blood triglycerides increased	0/26 (0%)		1/12 (8.3%)
Platelet count decreased	2/26 (7.7%)		0/12 (0%)
Weight decreased	0/26 (0%)		1/12 (8.3%)
Metabolism and nutrition disorders
Decreased appetite	4/26 (15.4%)		2/12 (16.7%)
Hypercholesterolaemia	0/26 (0%)		1/12 (8.3%)
Hypophosphataemia	1/26 (3.8%)		1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/26 (11.5%)		0/12 (0%)
Back pain	2/26 (7.7%)		1/12 (8.3%)
Muscle spasms	3/26 (11.5%)		1/12 (8.3%)
Pain in extremity	0/26 (0%)		1/12 (8.3%)
Nervous system disorders
Dysaesthesia	0/26 (0%)		1/12 (8.3%)
Dysgeusia	3/26 (11.5%)		0/12 (0%)
Headache	6/26 (23.1%)		0/12 (0%)
Polyneuropathy	2/26 (7.7%)		0/12 (0%)
Tremor	0/26 (0%)		1/12 (8.3%)
Psychiatric disorders
Depression	3/26 (11.5%)		0/12 (0%)
Insomnia	1/26 (3.8%)		1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	3/26 (11.5%)		1/12 (8.3%)
Dyspnoea exertional	0/26 (0%)		1/12 (8.3%)
Oropharyngeal pain	7/26 (26.9%)		0/12 (0%)
Paranasal sinus hypersecretion	2/26 (7.7%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Acne	0/26 (0%)		1/12 (8.3%)
Dermatitis acneiform	0/26 (0%)		1/12 (8.3%)
Pruritus	1/26 (3.8%)		1/12 (8.3%)
Rash	0/26 (0%)		1/12 (8.3%)
Vascular disorders
Flushing	0/26 (0%)		1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.