MDACC Study Summary 2007-0141 (Archived)

Study Summary
No. 2007-0141:.......Lymphoma; Skin......Madeleine Duvic......Dermatology

Study Summary Title



Study Summary Number:	2007-0141

Study Title:	A Phase II Study of LBH589B in Adult Patients with Refractory Cutaneous T-Cell Lymphoma and Prior HDAC Inhibitor 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:	Novartis

Phase of Study:	Phase II	Return Visit:	During Cycle 1 - 7 times, subsequent cycles at least once a week.

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

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	n/a


Description/ Intervention:	The goal of this clinical research study is to learn if LBH589 (panobinostat) can help to control cutaneous T-cell lymphoma (CTCL). The safety of this drug will also be studied.

Study Objectives / Outcomes

Primary Objective(s):
To determine the overall response rate of patients with resistant CTCL treated with oral LBH589 by using the modified Severity-Weighted Assessment Tool (mSWAT) to assess skin disease and the evaluation of disease in the viscera, lymph nodes, blood (circulating SS cells).

Secondary Objective(s):
To determine in patients with restistant CTCL the following:

Response rate using the Physicians Global Assessment of Clinical Condition (PGA)
Response rate using Modified Severity Weighted Assessment (mSWAT) skin score
Responses in index lesions as assessed by lesion measurements and photographic supporting documentation
To determine the overall response rate of patients with resistant CTCL treated with oral LBH589 by using the modified Physician's Global Assessment (PGA) to assess skin disease and the evaluation of disease in the viscera, lymph nodes and blood (circulating SS cells).
Duration of response
Time to response
Safety and tolerability

Exploratory Objective:
Potential biological factors that might correlate with efficacy and response. For this purpose, blood samples and tumor biopsies pre- and post-study treatment will be collected where available and accessible.

Study Status Information



Study Activation / Registration Date:	06/08/2007

IRB Review and Approval Date:	06/08/2007

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Terminated

Projected Accrual:	41

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 Sezary syndrome stages IIB-IVA. Patients who have SS with bone marrow involvement are also eligible. Patients with transformed CTCL are eligible. Disease state for eligibility is based on the stage at time of study enrollment. However, patients with any history of visceral involvement of their CTCL will not be eligible for this study.

4) Patients must have been treated with at least 2 prior systemic treatment regimens. One of these prior regimens must be an HDAC inhibitor given for the treatment of CTCL. Patients who have only had prior treatment with an HDAC inhibitor for non-CTCL indications (e.g., valproic acid for the treatment of seizures) are not eligible. Patients must have received prior therapy with an HDAC inhibitor (documentation of prior use or resistance to vorinostat (Zolinza), romidepsin (Chromadax), or another HDAC inhibitor (e.g. PDX101, Savicol, Baceca, MS-275, MGCD0103, & MG98).

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 must have the following laboratory values: absolute neutrophil count (ANC) >/= 1.5 x 10^ 9/L,Hemoglobin (Hgb) >/= 9 g/dl, Platelets >/= 100 x 10^9/L, Serum potassium >/= the lower limit of normal (LLN), Serum calcium (total 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), Serum bilirubin </= 1.5 x ULN, Serum creatinine </= 1.5 x ULN, TSH and free T4 WNL (patients may be on thyroid hormone replacement), Albumin >/= 3 g/dL (continued in #7)

7) Potassium, calcium, magnesium and phosphorus supplements may be given to correct values that are < LLN, but these must be documented as corrected prior to patients enrolling on the study.

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

9) ECOG Performance Status </= 2

Exclusion Criteria:

1) 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). Patients with SS who have bone marrow involvement are eligible.

2) Patients who have been previously treated with LBH589.

3) 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 Torsades de Pointes; bradycardia defined as HR < 50 beats per minute; patients with pacemakers are eligible if HR >/= 50 bpm (criteria continued in eligibility #3)

4) 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).

5) Uncontrolled hypertension (systolic > 140 mm Hg or diastolic > 90 mm Hg).

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 known risk of causing Torsades de Pointes.

8) Concomitant use 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 of oral LBH589

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

12) Other concurrent severe and/or uncontrolled medical conditions

13) 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 drug or who have not recovered from side effects of such therapy.

16) Women who are pregnant or breast feeding or women of childbearing potential (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. (criteria continued in exclusion #16)

17) 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). Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589.

18) Men 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.

19) 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.

20) 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: NCT00490776
Study Information on Clinical Trials Registry (clinicaltrials.gov)