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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
129
Panobinostat hard gelatin capsules.
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.
Time frame: From the start of the treatment of last participant up to 32 weeks
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.
Time frame: From start of treatment until progression/recurrence or start of a new cancer therapy (up to approximately 5 years)
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City of Hope National Medical Center Dept.ofCityofHopeMedicalCtr(2)
Duarte, California, United States
Emory University School of Medicine/Winship Cancer Institute Dept. of Hematology (2)
Atlanta, Georgia, United States
Georgia Regents University Cancer Clinical Research Unit
Augusta, Georgia, United States
Rush University Medical Center Divisionof Hem/Onc Research(2)
Chicago, Illinois, United States
VA Maryland Health Care Dept.of GreenbaumCancerCent(5)
Baltimore, Maryland, United States
Dana Farber Cancer Institute Hematology / Oncology
Boston, Massachusetts, United States
Karmanos Cancer Institute Div.of Hematology/Oncology
Detroit, Michigan, United States
Mayo Clinic - Rochester Hematology
Rochester, Minnesota, United States
University of Pennsylvania Medical Center Dept of UPenn Med Ctr (3)
Philadelphia, Pennsylvania, United States
University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(3)
Houston, Texas, United States
...and 36 more locations
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.
Time frame: From the start of treatment up to approximately 5 years
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.
Time frame: From the start of treatment up to approximately 5 years
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.
Time frame: From the start of treatment up to approximately 5 years
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.
Time frame: Baseline to date of death from any cause (up to approximately 5 years)
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.
Time frame: Up to approximately 5 years
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
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
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
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