Study to Allow Access to Single Agent Panobinostat for Patients Who Are on s.a. Panobinostat Treatment in a Novartis-sponsored Study and Continue to Benefit From the Treatment as Judged by the Investigator

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01802879
• Collaborator: (none)
• Enrollment: 9
• Locations: 7
• Arm: 1
• Actual Duration (Months): 64.9
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The study allowed continued use of single agent panobinostat in patients who were on single agent panobinostat treatment in a Novartis-sponsored study which had met its endpoint and were benefiting from the treatment as judged by the investigator.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Neoplasms	Drug: Panobinostat	Phase 2

Detailed Description

This was a multi-center open label study to provide continued use of single agent oral panobinostat to patients treated in a Novartis-sponsored study (parent study) which had met its endpoint and were benefiting from continuation of the treatment with single-agent panobinostat as judged by the investigator. Patients from multiple parent studies were transferred over to this protocol and continued to receive single agent panobinostat at the last assigned dose and regimen of the parent protocol. There was no screening period, and patients had to visit the study center at least on a quarterly basis. During these visits limited information on study treatment and occurrence of SAEs was collected for the clinical database. SAEs were only reported to the Novartis safety database. Other assessments and possibly more frequent visits occurred as per standard of care at the site. Patients continued treatment until they were no longer benefiting from panobinostat treatment, developed unacceptable toxicities, withdrew consent, were non-compliant with the protocol, the investigator believed it was no longer in the best interest to continue, the patient died, or for other administrative reasons. An end of treatment visit and a safety follow-up for 30 days after the last dose was performed. The study was expected to remain open for 5 years or until such time that enrolled patients no longer needed treatment with panobinostat, whichever came earlier.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Multi-center Single Agent Panobinostat Roll-over Protocol for Patients Who Have Completed a Previous Novartis-sponsored Panobinostat Study and Are Judged by the Investigator to Benefit From Continued Single Agent Panobinostat Treatment
• Actual Study Start Date: Jun 24, 2013
• Actual Primary Completion Date: Nov 19, 2018
• Actual Study Completion Date: Nov 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panobinostat - 10 to 40 mg/day TIW QoW 10 to 40mg/day TIW QoW (3 times/week every other week) as per parent protocol design	Drug: Panobinostat; Panobinostat was provided as 5, 10 and 20 mg hard gelatin capsules to be taken orally. Patients started on dose from parent protocol and dose modifications were at the discretion of the investigator based on guidance provided in the protocol and IB.

Outcome Measures

Primary Outcome Measures

1. Overview of Adverse Events (Safety Set) [Baseline up to approximately 60 months]

   Adverse events were collected from baseline up to 30 days post treatment at scheduled visits. Severity of adverse events was assessed according to the current version of Common Terminology Criteria for Adverse Events (CTCAE). If CTCAE grading did not exist for an adverse event, the severity of mild, moderate, severe, and life-threatening, corresponding to Grades 1 - 4, was used

Secondary Outcome Measures

1. Percentage of Patients With Clinical Benefit as Assessed by the Investigator. [baseline up to approximate 5 years]

   Patients were assessed by investigators at scheduled visits to determine if patient continued to benefit from panobinostat therapy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• patient had been enrolled in a Novartis-sponsored, Oncology OGD&GMA study receiving s.a. oral panobinostat and had fulfilled all their requirements in the parent study

• patient had been benefiting from the treatment with s.a. oral panobinostat as determined by the guidelines of the parent protocol and according to the Investigator's clinical judgment

• patient had demonstated compliance

• patient had given written informed consent.

Exclusion Criteria:

• patient had been permanently discontinued from s.a. oral panobinostat study treatment in the parent study due to unacceptable toxicity, withdrawal of consent, non-compliance to study procedures or any other reason (including progression of disease).

• patient had participated in a Novartis sponsored combincation trial where panobinostat was dispensed in combination with another study medication and was still receiving combination therapy

• patient was pregnant or nursing at the time of entry

• women of child-bearing potential and male patients with sexual partners of child-bearing potential who were unwilling to use highly effective methods of contraception during dosing and for a specified duration after stopping study treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center Dept.ofCityofHopeMedicalCtr(1)	Duarte	California	United States	91010 3000
2	Georgia Regents University SC-2	Augusta	Georgia	United States	30912
3	Dana Farber Cancer Institute Reg. Ped	Boston	Massachusetts	United States	02215
4	University of Utah / Huntsman Cancer Institute SC-2	Salt Lake City	Utah	United States	84103
5	Novartis Investigative Site	Jerusalem		Israel	91120
6	Novartis Investigative Site	Leiden		Netherlands	2300 RC
7	Novartis Investigative Site	Salamanca	Castilla Y Leon	Spain	37007

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Mar 11, 2016
• Statistical Analysis Plan - Jun 14, 2016

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01802879
• Other Study ID Numbers: CLBH589B2402B; 2012-005252-41
• First Posted: Mar 4, 2013
• Last Update Posted: Dec 6, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Hematologic Neoplasms, LBH589,; Panobinostat,
• Additional relevant MeSH terms: Hematologic Neoplasms; Panobinostat

Study Results

Participant Flow

Pre-assignment Detail	There was no screening period. Patients enrolled into trial directly from the parent protocol.

Arm/Group Title	Panobinostat - 10 to 40 mg/Day TIW QoW
Arm/Group Description	10 to 40mg/day TIW QoW (3 times/week every other week) as per parent protocol design
Period Title: Overall Study
STARTED	8
COMPLETED	0
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Panobinostat - 10 to 40 mg/Day TIW QoW
Arm/Group Description	10 to 40mg/day TIW QoW (3 times/week every other week) as per parent protocol design
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (14.5)
Sex: Female, Male (Count of Participants)
Female	4 50%
Male	4 50%
Race and Ethnicity Not Collected (Count of Participants)
Parent protocol participants (participants) [Number]
CLBH589B2201	2 25%
CLBH589B2207	3 37.5%
CLBH589E2214	1 12.5%
CLBH589X2105	2 25%

Outcome Measures

1. Secondary Outcome

Title	Percentage of Patients With Clinical Benefit as Assessed by the Investigator.
Description	Patients were assessed by investigators at scheduled visits to determine if patient continued to benefit from panobinostat therapy.
Time Frame	baseline up to approximate 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panobinostat - 10 to 40 mg/Day TIW QoW
Arm/Group Description	10 to 40mg/day TIW QoW (3 times/week every other week) as per parent protocol design
Measure Participants	8
Participants with clinical benefit	7 87.5%

2. Primary Outcome

Title	Overview of Adverse Events (Safety Set)
Description	Adverse events were collected from baseline up to 30 days post treatment at scheduled visits. Severity of adverse events was assessed according to the current version of Common Terminology Criteria for Adverse Events (CTCAE). If CTCAE grading did not exist for an adverse event, the severity of mild, moderate, severe, and life-threatening, corresponding to Grades 1 - 4, was used
Time Frame	Baseline up to approximately 60 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panobinostat - 10 to 40 mg/Day TIW QoW
Arm/Group Description	10 to 40mg/day TIW QoW (3 times/week every other week) as per parent protocol design
Measure Participants	8
Any adverse event (AE)	6 75%
Any treatment related AE	2 25%
Any serious adverse event (SAE)	2 25%
Grade 3 or 4 AE	3 37.5%
Grade 3 or 4 AE - suspected to be related	1 12.5%
AEs leading discontinuation	0 0%
AEs leading to dose adjust/ temp dose interruption	2 25%
On-treatment death	0 0%

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 84 weeks
Adverse Event Reporting Description	AE additional description
Arm/Group Title	Panobinostat - 10 to 40 mg/Day TIW QoW
Arm/Group Description	10 to 40mg/day TIW QoW (3 times/week every other week) as per parent protocol design
All Cause Mortality
	Panobinostat - 10 to 40 mg/Day TIW QoW
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Panobinostat - 10 to 40 mg/Day TIW QoW
	Affected / at Risk (%)	# Events
Total	2/8 (25%)
General disorders
Non-cardiac chest pain	1/8 (12.5%)
Nervous system disorders
Cerebrovascular accident	1/8 (12.5%)
Other (Not Including Serious) Adverse Events
	Panobinostat - 10 to 40 mg/Day TIW QoW
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
Blood and lymphatic system disorders
Neutropenia	1/8 (12.5%)
Gastrointestinal disorders
Diarrhoea	1/8 (12.5%)
Gastric disorder	1/8 (12.5%)
General disorders
Asthenia	1/8 (12.5%)
Infections and infestations
Nasopharyngitis	1/8 (12.5%)
Investigations
Blood creatinine increased	1/8 (12.5%)
Platelet count decreased	1/8 (12.5%)
Musculoskeletal and connective tissue disorders
Bone pain	1/8 (12.5%)
Osteoarthritis	1/8 (12.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign muscle neoplasm	1/8 (12.5%)
Nervous system disorders
Neuropathy peripheral	2/8 (25%)
Psychiatric disorders
Insomnia	1/8 (12.5%)
Skin and subcutaneous tissue disorders
Pruritus	1/8 (12.5%)

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 (ie, data from all sites) in the clinical trial.