A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in... | NCT00866333

NCT00866333

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Entinostat	Experimental	Regimen determined by protocol version. Regimen 1: entinostat 10 mg (two 5 mg tablets) orally, once every two weeks (Days 1 and 15) in a 28-day cycle until disease progression or unacceptable toxicity. Regimen 2: entinostat 10 mg (two 5 mg tablets) orally on Day 1, increased to 15 mg (three 5 mg tablets) beginning on Day 15 of Cycle 1 for participants who had not experienced treatment-related adverse events with severity grade ≥2 (moderate), then continue 15 mg every two weeks (Days 1 and 15) in a 28-day cycle until disease progression or unacceptable toxicity. Regimen 3: entinostat 15 mg (three 5 mg tablets), orally, once weekly for 3 weeks followed by a 1-week break in a 4-week (28-day) cycle until disease progression or unacceptable toxicity.	Drug: Entinostat

Name	Type	Description	Arm Group Labels	Other Names
Entinostat	Drug	Entinostat tablets	Entinostat	SNDX-275

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	Best Overall Response was defined as Complete Response (CR) or Partial Response (PR). Tumor response was assessed by the Investigators using the International Working Group revised response criteria for malignant lymphoma (Cheson, Pfistner et al. 2007). CR was defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to HL. PR was defined as: At least a 50% decrease in sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses, No increase in the size of other nodes, No new sites of disease.	Up to 6 months

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Best Overall Response Based on the Participant's Best Response Documented Through the Entire Course of Protocol Therapy	Best Overall Response was defined as Complete Response (CR) or Partial Response (PR). Tumor response was assessed by the Investigators using the International Working Group revised response criteria for malignant lymphoma (Cheson, Pfistner et al. 2007). CR was defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to HL. PR was defined as: At least a 50% decrease in sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses, No increase in the size of other nodes, No new sites of disease.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.
Must have progressed after, or been ineligible for, stem cell transplantation.
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.
Last dose of cytotoxic chemotherapy must be > 21 days before the first dose of study drug.
European Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Age 18 years or older.
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.
Serum Creatinine ≤ 1.5 x ULN.
Absolute neutrophil counts of ≥ 1,000/µL, and platelet counts ≥ 50,000/µL
Patients or their legal representative must be able to read, understand, and sign a written informed consent

Exclusion Criteria:

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.
Prior allogeneic stem cell transplantation requiring active immunosuppressive therapy within 3 months of registration or with evidence of active Graft Versus Host Disease (GVHD).
Pregnant or lactating women. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test prior to start of study drug.
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.
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.
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.
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).
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.
Known human immunodeficiency virus (HIV) or a history of active Hepatitis B or C as evidenced by laboratory abnormalities in addition to positive serology.
Active central nervous system lymphoma and lymphoma with leptomeningeal involvement.
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.
Any condition that will put the patient at undue risk or discomfort as a result of adherence to study procedures.
History of gastrointestinal disorders (medical disorder or extensive surgery) that could interfere with absorption of study drug.

Facility	Status	City	State	ZIP	Country	Contacts
Tower Cancer Research Foundation		Beverly Hills	California		United States
University of Colorado

PubMed Identifier	Type	Citation	Retractions
27151994	Derived	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.

Arm/Group Information

ID	Title	Description
FG000	Regimen 1: Entinostat 10 mg	Regimen 1: entinostat 10 mg (two 5 mg tablets) orally, once every two weeks (Days 1 and 15) in a 28-day cycle until disease progression or unacceptable toxicity.
FG001	Regimen 2: Entinostat 10 mg/15 mg	Regimen 2: entinostat 10 mg (two 5 mg tablets) orally on Day 1, increased to 15 mg (three 5 mg tablets) beginning on Day 15 of Cycle 1 for participants who had not experienced treatment-related adverse events with severity grade ≥2 (moderate), then continue 15 mg every two weeks (Days 1 and 15) in a 28-day cycle until disease progression or unacceptable toxicity.
FG002	Regimen 3: Entinostat 15 mg	Regimen 3: entinostat 15 mg (three 5 mg tablets), orally, once weekly for 3 weeks followed by a 1-week break in a 4-week (28-day) cycle until disease progression or unacceptable toxicity.

ID	Title	Description
BG000	Regimen 1: Entinostat 10 mg	Regimen 1: entinostat 10 mg (two 5 mg tablets) orally, once every two weeks (Days 1 and 15) in a 28-day cycle until disease progression or unacceptable toxicity.
BG001	Regimen 2: Entinostat 10 mg/15 mg

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

Best Overall Response was defined as Complete Response (CR) or Partial Response (PR). Tumor response was assessed by the Investigators using the International Working Group revised response criteria for malignant lymphoma (Cheson, Pfistner et al. 2007). CR was defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to HL. PR was defined as: At least a 50% decrease in sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses, No increase in the size of other nodes, No new sites of disease.

Per-Protocol (PP) population included all participants who met all of the following criteria: Completed at least 2 cycles of entinostat therapy and Underwent computed tomography (CT) or positron emission tomography (PET) scans at Screening and Day 1 of Cycle 3.

Posted

Number

95% Confidence Interval

percentage of participants

Up to 6 months

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Regimen 1: Entinostat 10 mg	Regimen 1: entinostat 10 mg (two 5 mg tablets) orally, once every two weeks (Days 1 and 15) in a 28-day cycle until disease progression or unacceptable toxicity.

ID	Term
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders

OG000	Regimen 1: Entinostat 10 mg	Regimen 1: entinostat 10 mg (two 5 mg tablets) orally, once every two weeks (Days 1 and 15) in a 28-day cycle until disease progression or unacceptable toxicity.
OG001	Regimen 2: Entinostat 10 mg/15 mg	Regimen 2: entinostat 10 mg (two 5 mg tablets) orally on Day 1, increased to 15 mg (three 5 mg tablets) beginning on Day 15 of Cycle 1 for participants who had not experienced treatment-related adverse events with severity grade ≥2 (moderate), then continue 15 mg every two weeks (Days 1 and 15) in a 28-day cycle until disease progression or unacceptable toxicity.
OG002	Regimen 3: Entinostat 15 mg	Regimen 3: entinostat 15 mg (three 5 mg tablets), orally, once weekly for 3 weeks followed by a 1-week break in a 4-week (28-day) cycle until disease progression or unacceptable toxicity.