Phase II Study of Oral Panobinostat in Adult Patients With Relapsed/Refractory Classical Hodgkin's Lymphoma
This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
First received: August 25, 2008
Last updated: May 28, 2014
Last verified: May 2014
This study will evaluate the efficacy of oral panobinostat in patients with refractory/relapsed classical HL who have received prior treatment with high dose chemotherapy and autologous stem cell transplant. Safety of panobinostat will also be assessed. Other markers that may correlate with efficacy or safety will be explored.
Classical Hodgkin's Lymphoma (i.e. Nodular Sclerosing, Mixed-cellularity, Lymphocyte-rich, Lymphocyte-depleted)
||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase II Study of Oral Panobinostat in Adult Patients With Relapsed/Refractory Classical Hodgkin's Lymphoma After High-dose Chemotherapy With Autologous Stem Cell.
Primary Outcome Measures:
- Objective response rate to therapy with oral panobinostat in patients with refractory/relapsed classical HL at 24 weeks post first-dose of study drug [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- response rate based on central review of CT scan/MRI [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- time to response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- duration of response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- progression-free survival, PFS rate at 6 month and 8 month [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Safety and tolerability of panobinostat treatment [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||August 2013 (Final data collection date for primary outcome measure)
Oral 40 mg/dose, three times per week, every week dosing on a 21-day cycle
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Patient age is ≥ 18 years
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- Patient has a history of classical HL (i.e. Nodular sclerosing, Mixed-cellularity, Lymphocyte-rich, Lymphocyte depleted)
Patient has progressive disease after receiving high dose chemotherapy with AHSCT Note: If last therapy was ≥ 18 months ago, then biopsy should be performed to confirm diagnosis.
Note: Patient should have received ≤5 prior systemic treatment regimens (See Post-text supplement 2 for definitions and examples) Note: Patients 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.
Patient has at least one site of measurable nodal disease at baseline ≥ 2.0 cm in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by CT scan (MRI is allowed only if CT scan can not be performed).
Note: Patients with bone marrow involvement are eligible, but this criteria alone should not be used for disease measurement
Patient 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/L [SI units 1.5 x 109/L]
- Platelet count ≥ 75 x 109/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 <LLN. Post-correction values must not be deemed to be a clinically significant abnormality prior to patients being dosed.
- Serum creatinine ≤ 1.5 x ULN
- Serum bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN, if patient has Gilbert syndrome)
- AST/SGOT and/or ALT/SGPT ≤ 2.5 x ULN or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement
- Clinically euthyroid Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
- Written informed consent was obtained from the patient prior to any study-specific screening procedures
- Patient has the ability to swallow capsules or tablets
- Patient has a history of prior treatment with a DAC inhibitor including panobinostat
- Patient will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat treatment
- Patient has been treated with monoclonal antibody therapy (e.g., rituximab or anti CD-30 antibody, etc.) within 4 weeks of start of study treatment
- Patient 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
- Patient has been treated with > 5 prior systemic lines of treatment (see Post-text supplement 2 for definitions and examples)
- Patient 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
- Patient is using any anti-cancer therapy concomitantly
- Patient 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)
- Patient 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
- Patient has a history of CNS involvement with lymphoma
Patient 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), QTcF > 450 msec on screening 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 MI within 6 months
- Congestive heart failure (New York Heart Association functional classification III-IV) or baseline MUGA/Echo shows LVEF < 45%
- Patient has any other clinically significant heart disease (e.g., uncontrolled hypertension)
- Patient 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)
- Patient has unresolved diarrhea ≥ grade 2
- Patient 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
- Patient has a known history of HIV seropositivity (screening HIV testing is not required)
- Patient 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
- Patient 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.
Male patient 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.
Patients with any of the following contraindications to PET are excluded from the [18F]-FDG PET study (only applicable for centers participating in the PET study):
- Fasting blood glucose above 200 mg/dL, at time of PET scan
- Inability to lay down for 60 minutes or has a history of claustrophobia
- Patient not at a participating center
Other protocol-defined inclusion/exclusion criteria may apply.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00742027
No publications provided by Novartis
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Harrison SJ, Hsu AK, Neeson P, Younes A, Sureda A, Engert A, Prince HM, Li M, Savage P, Bugarini R, Williams D, Squier M, Ritchie DS. Early thymus and activation-regulated chemokine (TARC) reduction and response following panobinostat treatment in patients with relapsed/refractory Hodgkin lymphoma following autologous stem cell transplant. Leuk Lymphoma. 2014 May;55(5):1053-60. doi: 10.3109/10428194.2013.820287. Epub 2013 Aug 5.
||Novartis ( Novartis Pharmaceuticals )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||August 25, 2008
||May 28, 2014
||United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Ministry of Social Affairs, Public Health and the Environment
Brazil: Ministry of Health
Egypt: Ministry of Health, Drug Policy and Planning Center
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ministry of Health
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Malaysia: Ministry of Health
New Zealand: Medsafe
Singapore: Health Sciences Authority
Spain: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Keywords provided by Novartis:
Classical Hodgkin Lymphoma
Classical Hodgkin's Lymphoma
Refractory Hodgkin's Lymphoma
Refractory Hodgkin Lymphoma
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on August 28, 2014
Neoplasms by Histologic Type
Immune System Diseases
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action