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

NCT00866333 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: SNDX-275-0501
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Hodgkin's Lymphoma

Keywords

Hodgkin's Lymphoma; Relapsed Hodgkin's Lymphoma; Refractory Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 (3)

• Percentage of Participants With Best Overall Response Based on the Participant's Best Response Documented Through the Entire Course of Protocol Therapy

  Regimen 1 and 2 median follow-up 36.6 months; Regimen 3 median follow-up 18.4 months

• Duration of Objective Response for Participants Achieving CR or PR

  Regimen 1 and 2 median follow-up 36.6 months; Regimen 3 median follow-up 18.4 months

• Number of Participants With Serious Adverse Events (SAE) and Adverse Events (AEs)

  First dose to within 30 days of the last dose of study drug (Up to 34 months)

Study Arms (1)

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

Interventions

Entinostat DRUG

Entinostat tablets

Also known as: SNDX-275

Entinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Syndax Pharmaceuticals: lead

Study Sites (6)

Tower Cancer Research Foundation

Beverly Hills, California, United States

Location

University of Colorado

Denver, Colorado, United States

Location

Johns Hopkins

Baltimore, Maryland, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, United States

Location

MD Anderson Cancer Center

Houston, Texas, United States

Location

Related Publications (1)

• 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.

  PMID: 27151994 DERIVED

MeSH Terms

Conditions

Hodgkin Disease

Interventions

entinostat

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Michael L. Meyers, MD, PhD, Chief Medical Officer
• Organization: Syndax Pharmaceuticals, Inc.

mmeyers@syndax.com

+1-646-690-7620

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The Single Group Assignment is one of three regimens based on the protocol version at the time of enrollment.

Study Record Dates

• First Submitted: March 19, 2009
• First Posted: March 20, 2009
• Study Start: April 13, 2009
• Primary Completion: February 8, 2013
• Study Completion: February 8, 2013
• Last Updated: October 22, 2019
• Results First Posted: October 22, 2019

Record last verified: 2019-10

Locations

US (6)