Trial Outcomes & Findings for A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin's Lymphoma (NCT NCT00866333)

Last Updated: 2019-10-22

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

49 participants

Primary outcome timeframe

Up to 6 months

Results posted on

2019-10-22

Participant Flow

Participants took part in the study at 6 investigative sites in the United States from 13 April 2009 to 8 February 2013.

Participants with a diagnosis of Relapsed or Refractory Hodgkin's Lymphoma (HL) were enrolled into one of three entinostat dosing regimens based on the version of the protocol at their time of enrollment in the study.

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	16	17	16
Overall Study COMPLETED	11	10	4
Overall Study NOT COMPLETED	5	7	12

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Overall Study Withdrawal of consent	0	1	2
Overall Study Reason not Specified	3	1	1
Overall Study Study Terminated by Sponsor	2	5	9

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Regimen 1: Entinostat 10 mg n=16 Participants 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/15 mg n=17 Participants 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 n=16 Participants 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.	Total n=49 Participants Total of all reporting groups
Age, Continuous	32.8 years STANDARD_DEVIATION 10.33 • n=5 Participants	37.4 years STANDARD_DEVIATION 13.53 • n=7 Participants	34.8 years STANDARD_DEVIATION 10.31 • n=5 Participants	35.0 years STANDARD_DEVIATION 11.45 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants	24 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	12 Participants n=7 Participants	6 Participants n=5 Participants	25 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White	10 Participants n=5 Participants	17 Participants n=7 Participants	15 Participants n=5 Participants	42 Participants n=4 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment United States	16 participants n=5 Participants	17 participants n=7 Participants	16 participants n=5 Participants	49 participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 6 months

Population: 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.

Outcome measures

Outcome measures
Measure	Regimen 1: Entinostat 10 mg n=12 Participants 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/15 mg n=17 Participants 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 n=12 Participants 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.
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	8.3 percentage of participants Interval 0.2 to 38.5	11.8 percentage of participants Interval 1.5 to 36.4	16.7 percentage of participants Interval 2.1 to 48.4

SECONDARY outcome

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

Population: PP population included all participants who met all of the following criteria: Completed at least 2 cycles of entinostat therapy and Underwent CT or PET scans at Screening and Day 1 of Cycle 3.

Outcome measures

Outcome measures
Measure	Regimen 1: Entinostat 10 mg n=12 Participants 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/15 mg n=17 Participants 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 n=12 Participants 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.
Percentage of Participants With Best Overall Response Based on the Participant's Best Response Documented Through the Entire Course of Protocol Therapy	8.3 percentage of participants Interval 0.2 to 38.5	17.6 percentage of participants Interval 3.8 to 43.4	16.7 percentage of participants Interval 2.1 to 48.4

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Regimen 1: Entinostat 10 mg n=1 Participants 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/15 mg n=3 Participants 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 n=2 Participants 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.
Duration of Objective Response for Participants Achieving CR or PR	NA months Median, Lower and Upper Confidence Interval (CI) were not estimable because there were no participants with CR or PR who progressed.	28.6 months Interval 20.2 to 28.6	8.3 months Lower and Upper CI were not estimable because there was only 1 participant with CR or PR who progressed.

SECONDARY outcome

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

Population: Safety Population included all participants who received at least one dose of study drug.

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.

Outcome measures

Outcome measures
Measure	Regimen 1: Entinostat 10 mg n=16 Participants 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/15 mg n=17 Participants 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 n=16 Participants 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.
Number of Participants With Serious Adverse Events (SAE) and Adverse Events (AEs) Any TEAE	16 Participants	17 Participants	16 Participants
Number of Participants With Serious Adverse Events (SAE) and Adverse Events (AEs) SAE	2 Participants	7 Participants	3 Participants

Adverse Events

Regimen 1: Entinostat 10 mg

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Regimen 2: Entinostat 10 mg/15 mg

Serious events: 7 serious events

Other events: 17 other events

Deaths: 0 deaths

Regimen 3: Entinostat 15 mg

Serious events: 3 serious events

Other events: 16 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Michael L. Meyers, MD, PhD, Chief Medical Officer

Syndax Pharmaceuticals, Inc.

Phone: +1-646-690-7620

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publication of the results of the multi-center Study shall not be made before the first multi-site publication by Sponsor or Publications Committee. No Public Presentation by Institution or Investigator will be made until Study Documentation/Results from all sites are received and analyzed by Sponsor. Separate publication by Investigator will be delayed for a period of 18 months until the initial publication by Committee or Sponsor, or a determination is made not to make such publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Regimen 1: Entinostat 10 mg n=16 participants at risk 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/15 mg n=17 participants at risk 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 n=16 participants at risk 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.
Blood and lymphatic system disorders Anemia	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	11.8% 2/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	11.8% 2/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	6.2% 1/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Cardiac disorders Cardio-respiratory arrest	6.2% 1/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Hepatobiliary disorders Cholangitis	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	5.9% 1/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Metabolism and nutrition disorders Dehydration	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	5.9% 1/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	6.2% 1/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	6.2% 1/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Metabolism and nutrition disorders Hyponatraemia	6.2% 1/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Endocrine disorders Hypothyroidism	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	5.9% 1/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Infections and infestations Liver abscess	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	5.9% 1/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Respiratory, thoracic and mediastinal disorders Lung infection pseudomonal	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	5.9% 1/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Renal and urinary disorders Nephrolithiasis	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	5.9% 1/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Blood and lymphatic system disorders Neutropenia	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	5.9% 1/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Psychiatric disorders Panic attack	6.2% 1/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Cardiac disorders Pericardial effusion	6.2% 1/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Cardiac disorders Pericarditis	6.2% 1/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	6.2% 1/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
General disorders Pyrexia	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	5.9% 1/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	6.2% 1/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Infections and infestations Sepsis	6.2% 1/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)
Vascular disorders Subdural haemorrhage	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)	5.9% 1/17 • First dose of study drug to within 30 days of last dose (Up to 34 months)	0.00% 0/16 • First dose of study drug to within 30 days of last dose (Up to 34 months)