Clinical trial NCT00866333: A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin's Lymphoma
Official title: A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patients With Relapsed or Refractory Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hodgkin's Lymphoma
Keywords: Hodgkin's Lymphoma
Relapsed Hodgkin's Lymphoma
Refractory Hodgkin's Lymphoma
Lead sponsor: Syndax Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2009-03-20
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The Single Group Assignment is one of three regimens based on the protocol version at the time of enrollment.
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of entinostat, SNDX-275, in patients with relapsed or refractory Hodgkin's lymphoma.


Eligibility criteria: Inclusion Criteria:

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 systemic therapy.
2. Must have progressed after, or been ineligible for, stem cell transplantation.
3. Documented disease that is radiographically measurable (≥ 1.5 cm in the largest transverse dimension). If only 1 site of radiographically measurable lesion with the longest diameter \< 2.5 cm, lesion must be positive by Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) or biopsy.
4. Last dose of cytotoxic chemotherapy must be \> 21 days before the first dose of study drug.
5. European Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Age 18 years or older.
7. Total Bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) and Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 2.5 x ULN, possible exceptions if documented Hodgkin Lymphoma (HL) liver involvement.
8. Serum Creatinine ≤ 1.5 x ULN.
9. Absolute neutrophil counts of ≥ 1,000/µL, and platelet counts ≥ 50,000/µL
10. Patients or their legal representative must be able to read, understand, and sign a written informed consent

Exclusion Criteria:

1. Patients with another active cancer (excluding basal cell carcinoma or CIN/cervical carcinoma in situ or melanoma in situ). Prior history of other cancer is allowed, excluding 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 prior to start of study drug.
4. 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.
5. Patients with uncontrolled intercurrent illness, active or uncontrolled infections, or a fever \> 38.5⁰C that has not been evaluated for infection on the day of scheduled dosing.
6. Patients who have been treated with any investigational drug within 28 days prior to the first dose of study medication, or who are receiving concurrent treatment with other experimental drugs or anti-cancer therapy.
7. Prior treatment with Histone Deacetylase (HDAC) inhibitors (e.g. valproic acid, Zolinza (SAHA), romidepsin (Istodax),and experimental compounds such as MethylGene's MCGD0103 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 human immunodeficiency virus (HIV) or a history of active Hepatitis B or C as evidenced by laboratory abnormalities in addition to positive serology.
10. Active central nervous system lymphoma and lymphoma with leptomeningeal involvement.
11. 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.
12. Any condition that will put the patient at undue risk or discomfort as a result of adherence to study procedures.
13. History of gastrointestinal disorders (medical disorder or extensive surgery) that could interfere with absorption of study drug.

Primary outcomes:
measure: Percentage of Participants With Best Overall Response Based on the Participant's Best Response That is Documented Within the First 6 Cycles of Protocol Therapy
timeFrame: Up to 6 months
Secondary outcomes:
measure: Percentage of Participants With Best Overall Response Based on the Participant's Best Response Documented Through the Entire Course of Protocol Therapy
timeFrame: Regimen 1 and 2 median follow-up 36.6 months; Regimen 3 median follow-up 18.4 months
measure: Duration of Objective Response for Participants Achieving CR or PR
timeFrame: Regimen 1 and 2 median follow-up 36.6 months; Regimen 3 median follow-up 18.4 months
measure: Number of Participants With Serious Adverse Events (SAE) and Adverse Events (AEs)
timeFrame: First dose to within 30 days of the last dose of study drug (Up to 34 months)
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
References:
citation: Batlevi CL, Kasamon Y, Bociek RG, Lee P, Gore L, Copeland A, Sorensen R, Ordentlich P, Cruickshank S, Kunkel L, Buglio D, Hernandez-Ilizaliturri F, Younes A. ENGAGE- 501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma. Haematologica. 2016 Aug;101(8):968-75. doi: 10.3324/haematol.2016.142406. Epub 2016 May 5.