A PHASE 2 MULTI-CENTER STUDY OF ENTINOSTAT (SNDX-275) IN PATIENTS WITH RELAPSED OR REFRACTORY HODGKIN’S LYMPHOMA
The goal of this clinical research study is to learn if entinostat can help to control Hodgkin’s lymphoma. The safety of this drug will also be studied.
Disease Group: Lymphoma
Treatment Agent: Entinostat,SNDX-275
Treatment Location: Both at MD Anderson & outside MD Anderson at one or more Collaborating Sites or Institutions
Estimatated Length of Stay in Houston: N/A
Sponsor: Syndax Pharmaceuticals, Inc
Return Visit: Screening, Day 1 of every cycle, Day 8 of Cycle 1, Day 15 of every cycle, End of Treatment and Followup
Home Care: N/A
Primary Objective Estimate the objective response rate with entinostat in patients with relapsed or refractory classical Hodgkin’s lymphoma. Objective response will include complete response (CR) and partial response (PR) and will be determined from each patient’s best response that is documented within the first 6 cycles of protocol therapy Secondary Objectives Examine the safety profile of entinostat Evaluate the objective response rate based on the patient’s best overall response that is documented throughout the entire course of protocol therapy Evaluate the duration of response for patients who achieve CR or PR Exploratory Assess the duration of overall survival (OS) and progression-free survival (PFS) Assess biologic markers that may predict efficacy or toxicity of entinostat To evaluate the pharmacokinetics of entinostat when administered as a monotherapy in Hodgkin’s lymphoma patients (optional procedure) Assess entinostat’s effects on immunomodulation
IRB Review and Approval Date: 01/14/2009
Recruitment Status: Not Accepting
Projected Accrual: 60
1) Pathologic confirmation of relapsed or refractory classical Hodgkin’s
lymphoma from the last biopsy available. Relapsed disease is defined as
progressive disease following systematic therapy(ies) with curative
intent. Refractory disease is defined as disease not responding to or
having progressed within 3 months of the last dose of most recent
2) Must have progressed after, or been ineligible for, stem cell transplantation. For transplant ineligible patients, criterion for ineligibility, e.g., comorbid condition, religious, social/economic, etc, must be provided.
3) Documented disease that is radiographically measurable (>=1.5 cm in the largest transverse dimension). If there is only 1 site of radiographically measurable lesion with the longest diameter < 2.5 cm, the lesion must be positive by FDG-PET or biopsy.
4) Last dose of cytotoxic chemotherapy must be > 21 days before the first dose of study drug administration. There is no upper limit to number of prior therapies. However, the patient must have recovered from acute toxicities from the most recent therapy to grade 1 or less.
5) ECOG performance status of 0 or 1 (must be done within 7 days prior to study drug administration).
6) Age 18 years or older
7) Total Bilirubin <= 1.5 x Upper Limit of Normal (ULN); AST (SGOT) and ALT (SGPT) <= 2.5 x ULN (results within 7 days before study drug administration ). However, exceptions may be made after discussion with the medical monitor in subjects with documented HL liver involvement.
8) Serum Creatinine </= 1.5 x ULN (results within 7 days before study drug administration)
9) Absolute neutrophil counts of >/= 1,000/mircoL (without growth factor support), and platelet counts >=50,000microL without transfusion support (results within 7 days before study drug administration. Platelet and RBC transfusion and hematopoietic growth factor support is allowed during study.
10) Patients or their legal representative must be able to read, understand, and sign a written informed consent
1) Patients with another active cancer (excluding basal cell carcinoma
or cervical intraepithelial neoplasia [CIN / cervical carcinoma in situ]
or melanoma in situ). Prior history of other cancer is allowed, as long
as there is no active disease within the prior 5 years.
2) Prior allogeneic stem cell transplantation requiring active immunosuppressive therapy within 3 months of registration or with evidence of active graft versus host disease (GVHD)
3) Pregnant or lactating women. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test documented within 7 days prior to start of study drug.
4) Women with child bearing potential (WOCBP) and men whose partners are WOCBP must use an acceptable method of contraception while enrolled on this study, and for a period of 3 months following the last dose of study drug. An example of an acceptable form of contraception is a double barrier method, such as condom with diaphragm.
5) Patients with uncontrolled intercurrent illness, active or uncontrolled infections or a fever >38.5 degrees C that has not been evaluated for infection on the day of scheduled dosing. Patients with documented history of tumor fever are acceptable, provided acute or chronic infection has been excluded as possible cause of the fever.
6) Patients who have been treated with any investigational drug within 28 days prior to the first dose of study drug, or who are receiving concurrent treatment with other experimental drugs or anti-cancer therapy.
7) Prior treatment with HDAC inhibitors (e.g. valproic acid, Zolinaz (SAHA), romidepsin (Istodax),and experimental compounds such as MethylGene’s MGCD0103 and Novartis’ LBH589).
8) History of pericarditis or pericardial effusion that had required medical or surgical intervention in the last 6 months, or myocardial infarction or arterial thromboembolic events within 6 months, or experiencing severe or unstable angina, or New York Heart Association (NYHA) Class III or IV disease, or a QTc interval > 0.47 seconds.
9) Known HIV or active Hepatitis B or C as evidenced by laboratory abnormalities in addition to positive serology. Testing is not required for patients not suspected of having these conditions.
10) Known HIV or a history of active Hepatitis B or C. Testing is not required for patients not suspected of having these conditions
11) Active central nervous system lymphoma and lymphoma with leptomeningeal involvement
12) Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc) that, in the judgment of the investigator, may affect the patient’s ability to sign the informed consent and comply with study procedures
13) Any condition that will put the patient at undue risk or discomfort as a result of adherence to study procedures
14) History of gastrointestinal disorders (medical disorder or extensive surgery) that could interfere with absorption of study drug.
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