MDACC Study Summary 2008-0805

Study Summary
No. 2008-0805:.......Lymphoma......Yasuhiro Oki......Lymphoma/Myeloma

Study Summary Title



Study Summary Number:	2008-0805

Study Title:	Phase I/II of Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients with Relapsed and Refractory Lymphoma

Physician

New Patient Referral



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

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

Phone:	713-792-2860 Contact us about clinical trials

General Information



Disease Group:	Lymphoma	Supported By:	Novartis

Phase of Study:	Phase I/Phase II	Return Visit:	Screening, Baseline, Day 1, 2, 3 of every cycle, Day 4 of every other cycle, Day 5 and 26 of cycle 1 , End of Treatment and Followup

Treatment Agents:	LBH589 "B" (oral) Panobinostat RAD001	Home Care:	N/A

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	N/A


Description/ Intervention:	The goal of Phase 1 of this clinical research study is to learn the highest tolerable dose of the combination of LBH589 (panobinostat) and RAD001 (everolimus) that can be given to patients with relapsed or refractory lymphoma. The safety of this drug combination will also be studied.

Study Objectives / Outcomes

Primary

Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the novel combination of everolimus + Panobinostat (LBH589) in a phase-I study in patients with relapsed lymphoma (Hodgkin and non-Hodgkin).
Determine the safety and efficacy of this novel combination in a phase-II study in patients with relapsed Hodgkin and non-Hodgkin lymphoma

Secondary

Determine the in vivo effect of therapy on selected serum cytokines/chemokines (TGF-beta, TARC, IL-6, IL-10, VEGF).
Examine pre-treatment level of selected molecular targets (HDACs 1-11, STAT6, pSTAT6, STAT3, pSTAT3, Myc, Akt, pAkt, S6, pS6, p21, cyclin D1) in primary lymphoma cells and the surrounding reactive inflammatory cells obtained by core needle biopsies from patients with relapsed lymphoma.
Examine the correlation between molecular and biologic markers and clinical response and/or treatment-related toxicity.

Study Status Information



Study Activation / Registration Date:	11/25/2009

IRB Review and Approval Date:	11/25/2009

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Closed

Projected Accrual:	N/A

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) Histologically confirmed Hodgkin or non Hodgkin's lymphoma

2) Relapsed or refractory after standard treatments and with no curative option with conventional therapy

3) No evidence of cerebral or meningeal involvement by lymphoma

4) Age >= 18 years

5) ECOG performance status 0 to 2

6) Life expectancy of at least 3 months

7) Signed informed consent form prior to enrollment

8) Patients must meet the following laboratory criteria: AST/SGOT and ALT/SGPT </= 2.5 x upper limit of normal (ULN) ) or </= 5.0 x ULN if the transaminase elevation is due to lymphoma involvement, Serum bilirubin </= 1.5 x ULN, Serum creatinine </=1.5 x ULN free T4 within normal limits (WNL) (patients may be on thyroid hormone replacement)

9) Patients must have at least one measurable site of disease

10) Adequate bone marrow function as shown by: ANC >/= 1.0 x 109/L, Platelets >/=100 x 109/L

11) Fasting serum cholesterol </=300 mg/dL OR </=7.75 mmol/L AND fasting triglycerides </= 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication 24 hours before starting therapy.

12) Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study drug

Exclusion Criteria:

1) Burkitt's lymphoma, Lymphoblastic lymphoma, Chronic lymphocytic leukemia (Small lymphocytic lymphoma may be included)

2) Chemotherapy or radiation therapy or other investigational agents within 4 weeks prior to entering the study

3) Previous radioimmunotherapy within 12 weeks

4) Prior therapy with HDAC or mTOR inhibitors i.e. temsirolimus, vorinostat (the list is not inclusive of investigational agents in these classes of drugs)

5) Patient with known HIV infection

6) Known active viral hepatitis

7) Any serious active disease or co-morbid condition, which in the opinion of the principle investigator, will interfere with the safety or with compliance with the study

8) Impaired cardiac function including any one of the following: • Screening ECG with a QTc > 450 msec confirmed by the investigator prior to enrollment to the study • Patients with congenital long QT syndrome • History of sustained ventricular tachycardia • Any history of ventricular fibrillation or torsades de pointes • Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate >= 50 beats per minute are eligible.

9) Impaired cardiac function including any one of the following continued: • Patients with a myocardial infarction or unstable angina within 6 months from registration on study • Congestive heart failure (NY Heart Association class III or IV) • Right bundle branch block and left anterior hemiblock (bifasicular block) • Uncontrolled hypertension

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

11) Patients with unresolved diarrhea CTCAE grade 1

12) Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral PANOBINOSTAT or everolimus.

13) Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception.

14) Male patients whose sexual partners are WOCBP not using effective birth control

15) Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, basal or squamous cell carcinoma of the skin, or early stage prostate carcinoma.

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

17) Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent

18) Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone <= 20 mg. Topical or inhaled corticosteroids are allowed.

19) Patients should not receive immunization with attenuated live vaccines within one week of study registration or during study period

20) COPD or asthma requiring therapy

21) Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN

22) Active (acute or chronic) uncontrolled severe infection, requiring oral or intravenous antibiotics.

23) Patients receiving treatment on another clinical research trial

Links

Registration Number: NCT00967044
Study Information on Clinical Trials Registry (clinicaltrials.gov)