Back to resultsA Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin's Lymphoma (ENGAGE-501)
Primary Purpose
Hodgkin's Lymphoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Entinostat
Sponsored by
About this trial
This is an interventional treatment trial for Hodgkin's Lymphoma focused on measuring Hodgkin's Lymphoma, Relapsed Hodgkin's Lymphoma, Refractory Hodgkin's Lymphoma
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.
Sites / Locations
- Tower Cancer Research Foundation
- University of Colorado
- Johns Hopkins
- University of Nebraska Medical Center
- Roswell Park Cancer Institute
- MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Entinostat
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Duration of Objective Response for Participants Achieving CR or PR
Duration of objective response was defined as the number of days from the start date of CR or PR (whichever status is recorded first), until the first date that recurrent or progressive disease was objectively documented.
Number of Participants With Serious Adverse Events (SAE) and Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A Treatment-Emergent Adverse Event (TEAE) is an AE that occurred after receive study drug. Any changes from baseline in vital signs, electrocardiogram results, and laboratory parameters assessed by the investigator to be clinically significant were reported as AEs. A SAE is defined as an AE that: is fatal, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity is a congenital anomaly/birth defect, is another significant medical hazard, such as new malignancy.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00866333
Brief Title
A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin's Lymphoma
Acronym
ENGAGE-501
Official Title
A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patients With Relapsed or Refractory Hodgkin's Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Terminated
Why Stopped
Terminated prior to completion of accrual per corporate decision.
Study Start Date
April 13, 2009 (undefined)
Primary Completion Date
February 8, 2013 (Actual)
Study Completion Date
February 8, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Syndax Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the efficacy and safety of entinostat, SNDX-275, in patients with relapsed or refractory Hodgkin's lymphoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin's Lymphoma
Keywords
Hodgkin's Lymphoma, Relapsed Hodgkin's Lymphoma, Refractory Hodgkin's Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
The Single Group Assignment is one of three regimens based on the protocol version at the time of enrollment.
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Entinostat
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Entinostat
Other Intervention Name(s)
SNDX-275
Intervention Description
Entinostat tablets
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Percentage of Participants With Best Overall Response Based on the Participant's Best Response Documented Through the Entire Course of Protocol Therapy
Description
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.
Time Frame
Regimen 1 and 2 median follow-up 36.6 months; Regimen 3 median follow-up 18.4 months
Title
Duration of Objective Response for Participants Achieving CR or PR
Description
Duration of objective response was defined as the number of days from the start date of CR or PR (whichever status is recorded first), until the first date that recurrent or progressive disease was objectively documented.
Time Frame
Regimen 1 and 2 median follow-up 36.6 months; Regimen 3 median follow-up 18.4 months
Title
Number of Participants With Serious Adverse Events (SAE) and Adverse Events (AEs)
Description
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A Treatment-Emergent Adverse Event (TEAE) is an AE that occurred after receive study drug. Any changes from baseline in vital signs, electrocardiogram results, and laboratory parameters assessed by the investigator to be clinically significant were reported as AEs. A SAE is defined as an AE that: is fatal, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity is a congenital anomaly/birth defect, is another significant medical hazard, such as new malignancy.
Time Frame
First dose to within 30 days of the last dose of study drug (Up to 34 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 Information:
Facility Name
Tower Cancer Research Foundation
City
Beverly Hills
State/Province
California
Country
United States
Facility Name
University of Colorado
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Johns Hopkins
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27151994
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.
Results Reference
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A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin's Lymphoma
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