Classical Hodgkin's Lymphoma
Conditions
Keywords
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
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.
Interventions
DRUGPanobinostat
Panobinostat hard gelatin capsules.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Maximum Observed Concentration (Cmax) of Panobinostat | 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 | 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 | 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 | Cycle 1, Day 1: Pre-dose, 0.25, 1, 3, 5, 7, 24, and 28 hours post-dose | — |
| 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. |
Countries
Australia, Belgium, Brazil, France, Germany, Israel, Italy, Malaysia, New Zealand, Singapore, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 45 sites in 13 countries from 16 September 2008 to 12 August 2013.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 129 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative Problems | 1 |
| Overall Study | Death | 7 |
| Overall Study | Disease Progression | 76 |
| Overall Study | Follow up Phase Completed As Per Protocol | 2 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Missing | 2 |
| Overall Study | New Cancer Therapy | 19 |
| Overall Study | Withdrawal by Subject | 18 |
Baseline characteristics
| Characteristic | Panobinostat |
|---|---|
| Age, Continuous | 34.7 years STANDARD_DEVIATION 12.24 |
| Sex: Female, Male Female | 63 Participants |
| Sex: Female, Male Male | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 129 / 129 |
| serious Total, serious adverse events | 51 / 129 |
Outcome results
Primary
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
Population: Full analysis set (FAS) included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Panobinostat | Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria | Complete Response | 5 Participants |
| Panobinostat | Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria | Partial Response | 30 Participants |
| Panobinostat | Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria | Stable Disease | 71 Participants |
| Panobinostat | Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria | Progressive Disease | 14 Participants |
| Panobinostat | Objective Response Rate (ORR) as Assessed by the Investigator Based on Cheson Response Criteria | Unknown | 9 Participants |
Secondary
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panobinostat | Area Under the Plasma Concentration-Time Curve From Time Zero to 28 Hours (AUC0-28) for Panobinostat | 233.38 hour*nanograms per milliliter (h.ng/mL) | Standard Deviation 112.138 |
Secondary
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panobinostat | Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-∞) for Panobinostat | 239.36 h.ng/mL | Standard Deviation 104.263 |
Secondary
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Panobinostat | Duration of Overall Disease Response | 30.1 weeks |
Secondary
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Panobinostat | Maximum Observed Concentration (Cmax) of Panobinostat | 41.88 nanograms per milliliter (ng/mL) | Standard Deviation 22.165 |
Secondary
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panobinostat | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), And Deaths as a Measure of Safety and Tolerability of Panobinostat | AEs | 100 percentage of participants |
| Panobinostat | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), And Deaths as a Measure of Safety and Tolerability of Panobinostat | SAEs | 39.5 percentage of participants |
| Panobinostat | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), And Deaths as a Measure of Safety and Tolerability of Panobinostat | Deaths | 45.0 percentage of participants |
Secondary
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
Population: FAS included all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panobinostat | Progression Free Survival (PFS) | 6.1 months |
Secondary
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)
Population: FAS included all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panobinostat | Response Rate Based on Central Review of Computed Tomography (CT) Scan/Magnetic Resonance Imaging (MRI) | Complete Response | 0.8 percentage of participants |
| Panobinostat | Response Rate Based on Central Review of Computed Tomography (CT) Scan/Magnetic Resonance Imaging (MRI) | Partial Response | 20.9 percentage of participants |
| Panobinostat | Response Rate Based on Central Review of Computed Tomography (CT) Scan/Magnetic Resonance Imaging (MRI) | Stable Disease | 56.6 percentage of participants |
| Panobinostat | Response Rate Based on Central Review of Computed Tomography (CT) Scan/Magnetic Resonance Imaging (MRI) | Progressive Disease | 15.5 percentage of participants |
| Panobinostat | Response Rate Based on Central Review of Computed Tomography (CT) Scan/Magnetic Resonance Imaging (MRI) | Unknown | 6.2 percentage of participants |
Secondary
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)
Population: FAS included all participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panobinostat | The Overall Survival (OS) | 34.9 months |
Secondary
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Panobinostat | The Time to Reach Maximum Plasma Concentration (Tmax) of Panobinostat | 1.1 hours |
Secondary
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Panobinostat | Time To Overall Disease Response in Responders | 9.9 weeks |