A Phase II Study Of Oral LBH589 In Adult Patients With Refractory Cutaneous T-Cell Lymphoma

Conditions: Adult patients with stages IB to IVA mycosis fungoides (MF) or Sézary syndrome (SS). All patients must have received at least two prior treatment regimens for their MF or SS, at least one of which was a systemic regimen.
MedDRA version: 8.1Level: LLTClassification code 10011679Term: Cutaneous T-cell lymphoma refractory

Registration Number: EUCTR2006-000880-27-DE

Lead Sponsor: ovartis Pharma Services AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 132

Inclusion Criteria

1. Written informed consent obtained prior to any screening procedures
2. Age = 18 years old
3. Patients with biopsy-confirmed stages IB-IVA mycosis fungoides or Sézary syndrome. Patients with SS who have bone marrow involvement are also eligible. Patients with transformed CTCL are eligible.
4. Patients must have received at least two prior systemic therapy regimens. Systemic regimens include oral bexarotene, PUVA, photophoresis, oral corticosteroids, total skin electron bean therapy, immunotherapy, chemotherapy such as methotrexate, and biological response modifiers such as interferon. Topical steroids alone are not considered as a treatment regimen.
5. Patients must have had disease progression on or following their most recent treatment regimen. Patients are also eligible if they had an inadequate response to their most recent treatment regimen defined as stable disease as the best response after at least 3 months of therapy.
6. Patients will be accrued to one of two groups:
• Group 1: Patients previously treated with oral bexarotene. This group includes patients who had:
1. Disease progression on or following treatment with oral bexarotene, OR
2. An inadequate response to oral bexarotene treatment defined as stable disease as the best response after at least 3 months of treatment, OR
3. Intolerance to oral bexarotene defined as patients who discontinued oral bexarotene treatment due to adverse events.
• Group 2: Patients who have not had prior oral bexarotene treatment.
7. Patients must have specific laboratory values (see protocol)
8. Baseline MUGA or ECHO must demonstrate LVEF = the lower limit of the institutional normal
9. ECOG Performance Status = 2
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

Exclusion Criteria

1. Prior treatment with an HDAC inhibitor for CTCL.
2. Patients who have been previously treated with LBH589.
3. Patients with any history of visceral disease including CNS involvement (i.e. history of stage IVB CTCL even if the IVB disease has been down-staged at the time of study enrollment). Note: Patients who have SS with bone marrow involvement are eligible.
4. Impaired cardiac function (details see protocol)
5. Uncontrolled hypertension
6. Concomitant use of any anti-cancer therapy or radiation therapy. Low potency topical steroid use is permitted. Topical bexarotene use is prohibited during the trial
7. Concomitant use of drugs with a risk of causing torsades des pointes
8. Concomitant us of CYP3A4/5 inhibitors
9. Patients with unresolved diarrhea > CTCAE grade 1
10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption or oral LBH589
11. Other concurrent severe and/or uncontrolled medical conditions
12. Patients who would need to receive valproic acid for any reason during the study or =5 days prior to starting study drug
12. Patients who have received chemotherapy or any investigational drug or undergone major surgery =3 weeks prior to starting study drug or who have not recovered from side effects of such therapy
14. Less than 3 months since prior electron beam therapy
15. Patients who have received wide field radiotherapy =4 weeks or limited field radiation for palliation =2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
Patients who have received biologic therapy, target therapy, vaccine, steroids or immunotherapy =2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
16. Women who are pregnant or breast feeding or women of childbearing potnetial (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at baseline.
17. Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom.