A Phase II Study of Oral Panobinostat in Adult Patients withRelapsed/Refractory Classical Hodgkin’s Lymphoma after high-dose chemotherapy with autologous stem cell transplant
- Conditions
- relapsed/refractory classical Hodgkin's lymphomaMedDRA version: 13.1Level: LLTClassification code 10020328Term: Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2008-003016-35-BE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 102
1. Patient age is = 18 years
2. Patient has an Eastern Cooperative Oncology Group (ECOG)
performance status of = 2
3. Patient has a history of classical HL (i.e. Nodular sclerosing, Mixedcellularity,
Lymphocyte-rich, Lymphocyte depleted)
4. Patient has progressive disease after receiving high dose
chemotherapy with AHSCT.
Note: If last therapy was = 18 months ago, then a biopsy should be performed to confirm diagnosis.
Note: Patient should have received <=5 prior systemic treatment regimens (See PTS 2 for definitions and examples)
5. 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.
6. 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 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 upper limit of normal (ULN)
or = 5.0 x ULN if the transaminase elevation is due to disease
involvement
7. Clinically euthyroid
Note: Patients are permitted to receive thyroid hormone supplements
to treat underlying hypothyroidism.
8. Written informed consent was obtained from the patient prior to any
study-specific screening procedures
9. Patient has the ability to swallow capsules or tablets
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Patient has a history of prior treatment with a DAC inhibitor including
panobinostat
2. Patient will need valproic acid for any medical condition during the
study or within 5 days prior to the first panobinostat treatment
3. 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
4. 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
5. Patient has been treated with > 5 prior systemic lines of treatment
(see Post-text supplement 2 for definitions and examples)
6. 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
7. Patient is using any anti-cancer therapy concomitantly
8. Patient has been treated with allogeneic hematopoietic stem cell
transplant who isq 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. 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
10. Patient has a history of CNS involvement with lymphoma
11. 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 unstable atrial fibrillation (ventricular heart rate >100
bpm). Patients with stable atrial fibrillation are allowed in the study
provided they do not meet the other cardiac exclusion criteria
• Previous history angina pectoris or acute MI within 6 months
• Congestive heart failure (New York Heart Association functional
classification III-IV)
12. Patient has any other clinically significant heart disease (e.g.,
uncontrolled hypertension)
13. 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)
14. Patient has unresolved diarrhea = grade 2
15. 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
16. Patient has a known history of HIV seropositivity (screening HIV
testing is not required)
17. 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
18. Women who are pregnant or breast feeding or women of
childbearing potential (WOCBP) not willing to use a double method
of contraception during the study and 3 months after the end of
t
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the objective response rate to therapy with oral<br>panobinostat in patients with refractory/relapsed classical HL using<br>modified response criteria for malignant lymphoma (see Post-text<br>supplement 1).;Secondary Objective: • To determine response rate based on central review of CT scan/MRI<br>• To assess the time to response<br>• To assess the duration of response<br>• To evaluate progression-free survival, PFS rate at 6 month and 8<br>month<br>• To assess the safety and tolerability of panobinostat treatment<br>• To assess overall survival<br>• To characterize the PK of panobinostat, including the parent drug<br>and any potential metabolite/s when feasible in at least 15<br>consenting patients with HL;Primary end point(s): CT scan to assess the response rate and for monitoring for progression <br>safety<br>pharmacokinetic parameters: Cmax, Tmax, and AUC0-24<br>Exploratory FDG-PET scan response and exploratory biomarkers<br>
- Secondary Outcome Measures
Name Time Method