MDACC Study Summary 2006-0647 (Archived)

Study Summary
No. 2006-0647:.......Lymphoma; Skin......Madeleine Duvic......Dermatology

Study Summary Title



Study Summary Number:	2006-0647

Study Title:	A phase II study of LBH589B (panobinostat) in adult patients with CTCL refractory to standard therapy

Physician

New Patient Referral



Name:	Madeleine Duvic	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Dermatology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-4578 Contact us about clinical trials

General Information



Disease Group:	Lymphoma Skin	Supported By:	N/A

Phase of Study:	Phase II	Return Visit:	cycle 1 - 6-7 visits, cycle 2 & subsequent cycles - 4 visits

Treatment Agents:	LBH589 "B" (oral)	Home Care:	n/a

Treatment Loc:	Independent Multicenter Arrangements

Estimated Length of Stay in Houston:	n/a


Description/ Intervention:	Unavailable

Study Objectives / Outcomes

Primary:
The primary objective of the study is to estimate the overall response rate of patients with refractory CTCL treated with oral panobinostat (otherwise known as LBH589 "B" form) based on the combined evaluation of visceral disease, lymph nodes, and by using the best overall modified Severity-Weighted Assessment Tool (SWAT) score to assess skin disease.

Secondary:
The following secondary objectives in patients with refractory CTCL will be assessed:

Response rate using modified Severity Weighted Assessment (mSWAT) skin score
Response rate using a composite of mSWAT to assess skin disease and the combined evaluation of disease in the viscera, lymph nodes and blood (circulating SS cells).
Response rate using the Physicians Global Assessment of Clinical Condition (PGA)
Response in index lesions by lesion measurements with supporting photographic documentation
To determine the overall response rate of patients with resistant CTCL treated with oral panobinostat by using the Physician's Global Assessment (PGA) to assess skin disease and the evaluation of disease in the viscera, lymph nodes and blood (circulating SS cells).
Improvement in CTCL-related symptoms and patient-reported outcomes
Duration of response
Time to response
Progression-free survival
Safety and tolerability
Pharmacokinetic (PK) profile of oral panobinostat
Potential biological factors that might correlate with efficacy and response.For this purpose,

blood samples and tumor biopsies pre- and post-therapy will be collected where available and
accessible.

Pharmacogenetics and pharmacogenomics (if applicable)

Study Status Information



Study Activation / Registration Date:	01/24/2007

IRB Review and Approval Date:	10/04/2006

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Terminated

Projected Accrual:	118

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Written informed consent obtained prior to any screening procedures

2) Age >/= 18 years old

3) Patients with biopsy-confirmed mycosis fungoides or S�zary syndrome stages IB-IVA. Patients who have SS with bone marrow involvement are also eligible. Patients with transformed CTCL are eligible. Disease stage for eligibility is based on the stage at time of study enrollment. However, patients with any history of visceral involvement due to CTCL will not be eligible for this study.

4) Patients must have received at least two prior systemic therapy regimens. Systemic regimens include oral bexarotene, PUVA, photophoresis, oral corticosteroids, total skin electron beam, immunotherapy, chemotherapy such as methotrexate, and biological response modifiers such as and 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 disease progression on or following treatment oral bexarotene, or an inadequate response to oral bexarotene treatment defined as stable disease as the best response after at least 3 months of treatment, or intolerance of oral bexoratene defined as patients who discontinued oral bexoratene treatment due to adverse events.Group 2: Patients who have not had prior oral bexarotene treatment.

7) Patients with an absolute neutrophil count (ANC) >/= 1.5 x 10^9/L, Hemoglobin (Hgb) >/= 9 g/dl, Platelets (plt) >/= 100 x 10^9/L, Serum potassium >/= the lower limit of normal (LLN), Serum total calcium (corrected for serum albumin) or ionized calcium >/= LLN, Serum magnesium >/= LLN, Serum phosphorus >/= LLN, AST/SGOT and ALT/SGPT </= 2.5 x upper limit of normal (ULN)

8) Patients with serum bilirubin </= 1.5 x ULN, Serum creatinine </= 1.5 x ULN, TSH and free T4 within normal limit (WNL) (patients may be on thyroid hormone replacement), Albumin > 3g/dL Potassium, calcium, magnesium & phosphorus supplements may be given to correct values that are < LLN, but there must be documented as corrected prior to patients enrolling on the study.For group 1 patients only: If the patient was previously treated with oral bexarotene and on thyroid hormone replacement, patient is eligible if TSH<LLN but free T4 must be within normal limit (WNL).

9) Baseline MUGA or ECHO must demonstrate LVEF >/= the lower limit of the institutional normal

10) ECOG Performance Status </= 2

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. a 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, including any one of the following: Screening ECG with a QTc > 450 msec confirmed by central laboratory prior to enrollment to the study, patients with congenital long QT syndrome, history of sustained ventricular tachycardia (Patients with a history of atrial arrhythmia are eligible but should be discussed with the Sponsor prior to enrollment), any history of ventricular fibrillation or torsade de pointes, bradycardia defined as HR < 50 beats per minute. Patients with pacemakers are eligible if HR >/= 50 bpm.

5) Patients with a myocardial infarction or unstable angina within 6 months of study entry, congestive heart failure (NY Heart Association class III or IV), right bundle branch block and left anterior hemiblock (bifasicular block)

6) Uncontrolled hypertension

7) 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.

8) Concomitant use of drugs with a risk of causing torsades de pointes

9) Concomitant use of CYP3A4/5 inhibitors

10) Patients with unresolved diarrhea > CTCAE grade 1

11) Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589

12) Other concurrent severe and/or uncontrolled medical conditions

13) Patients who would need to receive valproic acid for any reason during the study or </= 5 days prior to starting study drug.

14) 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

15) Less than 3 months since prior electron beam therapy

16) 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 treatment or who have not recovered from side effects of such therapy. For group 1 patients only: Patients who have received oral bexarotene </= 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.

17) Women who are pregnant, breast feeding, or of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study & 3 months after EOT. (This exclusion criteria continues in exclusion criteria 16).

18) 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 have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive mo.). Women of childbearing potential (WOCBP) must have a neg. serum pregnancy test at baseline.(This criteria is the continuation of exclusion 16).

19) 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.

20) Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, completely excised melanoma-in-situ, or basal or squamous cell carcinoma of the skin

21) Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required.

Links

Registration Number: NCT00425555
Study Information on Clinical Trials Registry (clinicaltrials.gov)