A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin's Lymphoma

Hodgkin's Lymphoma Clinical Trial

— ENGAGE-501  

Official title:

A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patients With Relapsed or Refractory Hodgkin's Lymphoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00866333
• Other study ID #: SNDX-275-0501
• Status: Terminated
• Phase: Phase 2
• Start date: April 13, 2009
• Est. completion date: February 8, 2013

Study information

• Verified date: October 2019
• Source: Syndax Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 49
• Est. completion date: February 8, 2013
• Est. primary completion date: February 8, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 > 38.5°C 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.

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin's Lymphoma
• Lymphoma

Intervention

Drug:
• Entinostat
Entinostat tablets

Locations

Country	Name	City	State
United States	Johns Hopkins	Baltimore	Maryland
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Colorado	Denver	Colorado
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Nebraska Medical Center	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Syndax Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Up to 6 months
Secondary	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.	Regimen 1 and 2 median follow-up 36.6 months; Regimen 3 median follow-up 18.4 months
Secondary	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.	Regimen 1 and 2 median follow-up 36.6 months; Regimen 3 median follow-up 18.4 months
Secondary	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.	First dose to within 30 days of the last dose of study drug (Up to 34 months)