Hodgkin's LymphomaPhase 2ENGAGE-501NCT00866333
A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin's Lymphoma
A Phase 2 study testing Entinostat in people with Hodgkin's Lymphoma, run by Syndax Pharmaceuticals at 6 sites in United States.
Trial summary
This study will evaluate the efficacy and safety of entinostat, SNDX-275, in patients with relapsed or refractory Hodgkin's lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin's Lymphoma
- What is being tested?
- Entinostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 6 sitesUnited States
- Study dates
- 13 Apr 2009to 8 Feb 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Johns Hopkins
Baltimore, Maryland
Tower Cancer Research Foundation
Beverly Hills, California
Roswell Park Cancer Institute
Buffalo, New York
University of Colorado
Denver, Colorado
MD Anderson Cancer Center
Houston, Texas
University of Nebraska Medical Center
Omaha, Nebraska
About this study
Official title: A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patients With Relapsed or Refractory Hodgkin's Lymphoma
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
- Being tested
- Entinostat
- Keywords
- Hodgkin's Lymphoma, Relapsed Hodgkin's Lymphoma, Refractory Hodgkin's Lymphoma
- Medical subject headings
- Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntinostatDrug
Also called SNDX-275
Entinostat tablets
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Entinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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)
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.
Measured: First dose to within 30 days of the last dose of study drug (Up to 34 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2009 (estimated)
- Study start13 Apr 2009
- Primary completion8 Feb 2013
- Study completion8 Feb 2013
Why it stopped: Terminated prior to completion of accrual per corporate decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hodgkin's LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syndax Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00866333
- Sponsor's protocol ID
- SNDX-275-0501
- Acronym
- ENGAGE-501
- Status last verified
- Oct 2019
- First submitted
- 19 Mar 2009
- Last updated
- 22 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 27151994
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patients With Relapsed or Refractory Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT00866333
- Acronym / sponsor ID
- ENGAGE-501 / SNDX-275-0501
- Conditions
- Hodgkin's Lymphoma
- Keywords
- Hodgkin's Lymphoma, Relapsed Hodgkin's Lymphoma, Refractory Hodgkin's Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated prior to completion of accrual per corporate decision.
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Syndax PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 13 Apr 2009
- Primary completion
- 8 Feb 2013 (actual)
- Study completion
- 8 Feb 2013 (actual)
- First posted
- 20 Mar 2009 (estimated)
- Results
- Posted 22 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the efficacy and safety of entinostat, SNDX-275, in patients with relapsed or refractory Hodgkin's lymphoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The Single Group Assignment is one of three regimens based on the protocol version at the time of enrollment.
| Arm | Type | Receives |
|---|---|---|
| Entinostat | Experimental | Drug: EntinostatRegimen 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EntinostatAlso: SNDX-275Entinostat tablets | Drug | Entinostat |
Primary outcome
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
Time frame: Up to 6 months
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.
3 secondary outcomes
Percentage of Participants With Best Overall Response Based on the Participant's Best Response Documented Through the Entire Course of Protocol Therapy
Time frame: 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
Time frame: 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)
Time frame: First dose to within 30 days of the last dose of study drug (Up to 34 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27151994Batlevi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Entinostat in people with Hodgkin's Lymphoma, run by Syndax Pharmaceuticals at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00866333, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2019.