Trial Outcomes & Findings for UCDCC#271: Phase I/II Trial of Epacadostat, Intralesional SD101, Radiotherapy in Patients With Lymphoma (NCT NCT03322384)

Last Updated: 2022-02-01

Results Overview

To determine the maximum tolerated dose (MTD) of epacadostat that can be given with radiotherapy and intralesional SD-101 immunotherapy for the phase I portion of the study. The MTD will be determined using a standard 3+3 design. Patients will be monitored weekly during a 30-day dose-limiting toxicity (DLT) period. MTD can be defined as The maximum dose at which \<2 of 6 patients experienced a DLT.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Up to 30 days of treatment

Results posted on

2022-02-01

Participant Flow

Participant milestones

Participant milestones
Measure	Experimental All patients will begin epacadostat on day 1 of radiotherapy, which will consist of three threatments over one week. Epacadostat will continue until disease progression or intolerance occurs. On days 1, 8, 15, 22, 29, intralesional injectinons of SD101 will be given to patients. epacadostat: Epacadostat will be administered orally, in pill form, twice daily until disease progression. SD-101: Four milligrams of SD-101 will be delivered into the treatment lesion by intralesional injection on days 1, 8, 15, 22, and 29. Radiotherapy: Radiotherapy will be delivered to the treatment lesion during the first week of ERS therapy.
Overall Study STARTED	20
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

UCDCC#271: Phase I/II Trial of Epacadostat, Intralesional SD101, Radiotherapy in Patients With Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental n=20 Participants All patients will begin epacadostat on day 1 of radiotherapy, which will consist of three threatments over one week. Epacadostat will continue until disease progression or intolerance occurs. On days 1, 8, 15, 22, 29, intralesional injectinons of SD101 will be given to patients. epacadostat: Epacadostat will be administered orally, in pill form, twice daily until disease progression. SD-101: Four milligrams of SD-101 will be delivered into the treatment lesion by intralesional injection on days 1, 8, 15, 22, and 29. Radiotherapy: Radiotherapy will be delivered to the treatment lesion during the first week of ERS therapy.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 30 days of treatment

Outcome measures

Outcome measures
Measure	Experimental n=6 Participants All patients will begin epacadostat on day 1 of radiotherapy, which will consist of three threatments over one week. Epacadostat will continue until disease progression or intolerance occurs. On days 1, 8, 15, 22, 29, intralesional injectinons of SD101 will be given to patients. epacadostat: Epacadostat will be administered orally, in pill form, twice daily until disease progression. SD-101: Four milligrams of SD-101 will be delivered into the treatment lesion by intralesional injection on days 1, 8, 15, 22, and 29. Radiotherapy: Radiotherapy will be delivered to the treatment lesion during the first week of ERS therapy.
Maximum Tolerated Dose (MTD)	300 mg

PRIMARY outcome

Timeframe: Through study completion, an average of one year

To characterize the safety profile of this regimen using CTCAE v4.03 (Common Toxicity Criteria for Adverse Events version 4.03) in the phase II expansion . The expansion phase (phase II) will be conducted using the MTD defined as the highest dose at which no more than one of six patients develops a DLT or Dose Level 1 if the MTD is not reached. Patients will be monitored every week during the first 30 days of study and then monthly thereafter up to a period of 1 year.

Outcome measures

Outcome measures
Measure	Experimental n=20 Participants All patients will begin epacadostat on day 1 of radiotherapy, which will consist of three threatments over one week. Epacadostat will continue until disease progression or intolerance occurs. On days 1, 8, 15, 22, 29, intralesional injectinons of SD101 will be given to patients. epacadostat: Epacadostat will be administered orally, in pill form, twice daily until disease progression. SD-101: Four milligrams of SD-101 will be delivered into the treatment lesion by intralesional injection on days 1, 8, 15, 22, and 29. Radiotherapy: Radiotherapy will be delivered to the treatment lesion during the first week of ERS therapy.
Incidence of Related Adverse Events [Safety and Tolerability]	17 Participants

SECONDARY outcome

Timeframe: Through study completion, an average of one year

Abscopal Response Rate (ARR) is defined as objective response rate (the percentage of patient that achieve a partial or complete response) at unirradiated sites using irRECIST criteria using imaging obtained every 60 days during the 1 year study period.

Outcome measures

Outcome measures
Measure	Experimental n=14 Participants All patients will begin epacadostat on day 1 of radiotherapy, which will consist of three threatments over one week. Epacadostat will continue until disease progression or intolerance occurs. On days 1, 8, 15, 22, 29, intralesional injectinons of SD101 will be given to patients. epacadostat: Epacadostat will be administered orally, in pill form, twice daily until disease progression. SD-101: Four milligrams of SD-101 will be delivered into the treatment lesion by intralesional injection on days 1, 8, 15, 22, and 29. Radiotherapy: Radiotherapy will be delivered to the treatment lesion during the first week of ERS therapy.
Abscopal Response Rate	4 Participants

Adverse Events

Experimental

Serious events: 9 serious events

Other events: 18 other events

Deaths: 10 deaths

Serious adverse events

Serious adverse events
Measure	Experimental n=20 participants at risk All patients will begin epacadostat on day 1 of radiotherapy, which will consist of three threatments over one week. Epacadostat will continue until disease progression or intolerance occurs. On days 1, 8, 15, 22, 29, intralesional injectinons of SD101 will be given to patients. epacadostat: Epacadostat will be administered orally, in pill form, twice daily until disease progression. SD-101: Four milligrams of SD-101 will be delivered into the treatment lesion by intralesional injection on days 1, 8, 15, 22, and 29. Radiotherapy: Radiotherapy will be delivered to the treatment lesion during the first week of ERS therapy.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify: lower GI bleed	5.0% 1/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Infections and infestations Sepsis	5.0% 1/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Infections and infestations Upper respiratory infection	5.0% 1/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Investigations Investigations - Other, specify: transanimitis	5.0% 1/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Metabolism and nutrition disorders Hyponatremia	5.0% 1/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify: electrolyte and fluid disorder	5.0% 1/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Musculoskeletal and connective tissue disorders Generalized muscle weakness	5.0% 1/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	5.0% 1/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify:disease progres	5.0% 1/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Renal and urinary disorders Acute kidney injury	5.0% 1/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Renal and urinary disorders Urinary retention	5.0% 1/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03

Other adverse events

Other adverse events
Measure	Experimental n=20 participants at risk All patients will begin epacadostat on day 1 of radiotherapy, which will consist of three threatments over one week. Epacadostat will continue until disease progression or intolerance occurs. On days 1, 8, 15, 22, 29, intralesional injectinons of SD101 will be given to patients. epacadostat: Epacadostat will be administered orally, in pill form, twice daily until disease progression. SD-101: Four milligrams of SD-101 will be delivered into the treatment lesion by intralesional injection on days 1, 8, 15, 22, and 29. Radiotherapy: Radiotherapy will be delivered to the treatment lesion during the first week of ERS therapy.
Blood and lymphatic system disorders Anemia	25.0% 5/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Cardiac disorders Sinus tachycardia	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Gastrointestinal disorders Constipation	25.0% 5/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Gastrointestinal disorders Diarrhea	15.0% 3/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Gastrointestinal disorders Dysphagia	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Gastrointestinal disorders Nausea	65.0% 13/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Gastrointestinal disorders Vomiting	45.0% 9/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
General disorders Chills	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
General disorders Edema limbs	30.0% 6/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
General disorders Fatigue	55.0% 11/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
General disorders Injection site reaction	25.0% 5/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Investigations Alkaline phosphatase increased	15.0% 3/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Investigations Aspartate aminotransferase increased	20.0% 4/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Investigations Creatinine increased	20.0% 4/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Investigations Lymphocyte count decreased	50.0% 10/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Investigations Neutrophil count decreased	35.0% 7/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Investigations Weight loss	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Investigations White blood cell decreased	30.0% 6/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Metabolism and nutrition disorders Anorexia	45.0% 9/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Metabolism and nutrition disorders Dehydration	15.0% 3/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Metabolism and nutrition disorders Hyperglycemia	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Metabolism and nutrition disorders Hypoalbuminemia	15.0% 3/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Metabolism and nutrition disorders Hyponatremia	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Musculoskeletal and connective tissue disorders Generalized muscle weakness	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Nervous system disorders Dizziness	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Nervous system disorders Dysgeusia	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Nervous system disorders Headache	25.0% 5/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Nervous system disorders Paresthesia	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Psychiatric disorders Confusion	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Psychiatric disorders Depression	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03
Skin and subcutaneous tissue disorders Skin hyperpigmentation	10.0% 2/20 • Up to 1 year. Incidence of Treatment-Emergent Adverse Events according CTCAE v4.03

Additional Information

Analyst

University of California, Davis

Phone: 9167348053

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place