search
Back to results

A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma (SIDNEY)

Primary Purpose

Follicular Lymphoma, Marginal Zone Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
EO2463
lenalidomide
rituximab
Sponsored by
Enterome
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Follicular Lymphoma focused on measuring Follicular Lymphoma, Marginal Zone Lymphoma, Rituximab, Lenalidomide, Vaccine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. For inclusion in Cohorts 1 and 4 patients should have relapsed/refractory, biopsy-proven grade 1, 2 or 3A, FL or MZL, ECOG performance status 0 to 2, and have received at least one prior line of treatment.
  2. For inclusion in Cohort 2 patients should have newly diagnosed, previously untreated (radiotherapy as only prior treatment is allowed), biopsy-proven grade 1, 2 or 3A, FL or MZL. ECOG performance status 0 or 1, and not be in need of standard of care therapy according to the assessment of the treating physician.
  3. Patients with only one prior treatment and a high-risk profile as defined by first progression of disease within 24 months of diagnosis (the exclusion is not applicable for patients with more than one prior line treatment).
  4. For inclusion in Cohort 3 patients should have newly diagnosed, previously untreated (radiotherapy as only prior treatment is allowed), biopsy-proven grade 1, 2 or 3A, FL or MZL. ECOG performance status 0 or 1, low tumor burden by Groupe d'Etude des Lymphomes Folliculaires criteria and be in need of therapy according to the assessment of the treating physician.
  5. Patients with an age ≥ 18 years old.
  6. Patients who are human leukocyte antigen (HLA)-A2 positive.
  7. Patients should have radiologically measurable disease with a lymph node or tumor mass greater than or equal to 1.5 cm in at least one dimension.
  8. Males or non-pregnant, non-lactating, females.
  9. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
  10. Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures.

Exclusion Criteria:

  1. Patients treated with dexamethasone > 2 mg/day or equivalent (i.e. 13 mg/day of prednisone, or 53 mg/day of hydrocortisone) within 14 days before the first EO2463 administration, unless required to treat an adverse event.
  2. Patients with grade 3B FL or transformation to an aggressive lymphoma subtype.
  3. Patients with only one prior treatment and a high-risk profile as defined by first progression of disease within 24 months of diagnosis (the exclusion is not applicable for patients with more than one prior line treatment).
  4. Patients with prior exposure to EO2463.
  5. Patients treated with immunotherapy (meaning immunostimulatory or immunosuppressive therapy; beside excluded, or allowed, compounds per other inclusion/exclusion criteria specifications), radionuclide therapy, radiotherapy, cytoreductive therapy, or received treatment with any other investigational agent within 28 days before the first EO2463 administration.
  6. Patients to be included in Cohorts 1 and 4, and who have received rituximab or other B cell ablation therapy within 8 weeks of start of study treatment.
  7. Patients with abnormal laboratory values.
  8. Patients with persistent Grade 3 or 4 toxicities.
  9. Uncontrolled central nervous system (CNS) metastasis.
  10. Other malignancy or prior malignancy with a disease-free interval of less than 3 years.
  11. Patients with clinically significant disease.
  12. Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g. Guillain-Barré syndrome).
  13. Patients with history of solid organ transplantation or hematopoietic stem cell transplantation.
  14. Pregnant and breastfeeding patients.
  15. Patients with history or presence of human immunodeficiency virus and/or potentially active hepatitis B virus/hepatitis C virus infection.

Sites / Locations

  • Dana Farber Cancer Institute
  • Mayo ClinicRecruiting
  • University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center)Recruiting
  • University of Washington-Seattle Cancer Care AllianceRecruiting
  • University of Bologna
  • IRCCS Policlinico San Matteo Foundation - University of PaviaRecruiting
  • IRCCS Policlinico San Matteo Foundation - University of PaviaRecruiting
  • University Hospital Vall d'Hebron, Institute of OncologyRecruiting
  • Clinica Universidad de NavarraRecruiting
  • Hospital Clinico Universitario de SalamancaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Arm Description

Safety Lead-In, Dose-Finding, Cohort, with a 3-by-3 design of EO2463 for 6 weeks followed by addition of lenalidomide week 7 and rituximab week 19 (depending on response). Four to 18 evaluable (previously treated) patients with Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) will be Included based on safety findings

15 Previously untreated patients with FL Or MZL. Evaluation of EO2463 monotherapy at the established dose in Cohort 1

15 Previously untreated patients with FL or MZL. Evaluation of EO2463 at the established dose in cohort 1 as monotherapy for 6 weeks and in combination with rituximab from week 7

15 Previously treated patients with FL Or MZL. Evaluation of EO2463 at the established dose in Cohort 1 in combination with lenalidomide and with addition of rituximab from week 19 onwards (depending on response)

Outcomes

Primary Outcome Measures

Phase 1: Recommended Phase 2 Dose | Adverse Events Assessment |
Incidences of adverse events, Treatment-Emergent Adverse events, Serious Adverse Events, Deaths, and Laboratory Abnormalities Using the National Cancer Institute-Common Terminology Criteria for Adverse events (NCI-CTCAE) V5.0.
Phase 2: Overall Response Rate
Overall Response Rate According to the Lugano Classification 2014 during EO2463 Monotherapy

Secondary Outcome Measures

Safety and Tolerability for EO2463 Administered as Monotherapy and in Combination with Lenalidomide, Rituximab and Lenalidomide/Rituximab
Incidences Of Adverse Events, Treatment-Emergent Adverse events, Serious Adverse events, Deaths, Treatment Discontinuations/Delays, And Laboratory Abnormalities Using The NCI-CTCAE V5.0 Grading System
Assessment of the Immunogenicity in Relation to OMP72, OMP64, OMP65, OMP66, and UCP2 that Compose EO2463
Immunogenicity will be assessed by interferon-Gamma (IFN-Γ) enzyme-Linked immunospot , and by intracellular cytokines staining, and multimers staining assays
Overall Response Rate
Overall Response Rate as described by the Lugano Classification 2014, and by the Lymphoma Response to Immunomodulatory Therapy Criteria (Lyric) 2016 by trial cohort
Duration of response
Duration of Response as described by the Lugano Classification 2014, and by the Lymphoma Response to Immunomodulatory Therapy Criteria (Lyric) 2016 by trial cohort
Evaluation of Overall Survival
The time interval from the date of first study treatment administration to the date of death due to any cause

Full Information

First Posted
December 8, 2020
Last Updated
February 17, 2023
Sponsor
Enterome
search

1. Study Identification

Unique Protocol Identification Number
NCT04669171
Brief Title
A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma
Acronym
SIDNEY
Official Title
A Global Multicenter Phase 1/2 Trial of EO2463, a Novel Microbial-Derived Peptide Therapeutic Vaccine, as Monotherapy, and in Combination With Lenalidomide and Rituximab, for Treatment of Patients With Indolent Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 5, 2021 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
September 30, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Enterome

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to define the recommended Phase 2 Dose, safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 during monotherapy and in combination with lenalidomide and/or rituximab in patients with indolent NHL
Detailed Description
EO2463 Is an innovative cancer peptide therapeutic vaccine based on the homologies between tumor associated antigens and microbiome-derived peptides that will be administered alone and in combination with lenalidomide, rituximab, and lenalidomide/rituximab to generate safety and preliminary efficacy data in patients with indolent NHL

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma, Marginal Zone Lymphoma
Keywords
Follicular Lymphoma, Marginal Zone Lymphoma, Rituximab, Lenalidomide, Vaccine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Safety Lead-In, Dose-Finding, Cohort, with a 3-by-3 design of EO2463 for 6 weeks followed by addition of lenalidomide week 7 and rituximab week 19 (depending on response). Four to 18 evaluable (previously treated) patients with Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) will be Included based on safety findings
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
15 Previously untreated patients with FL Or MZL. Evaluation of EO2463 monotherapy at the established dose in Cohort 1
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
15 Previously untreated patients with FL or MZL. Evaluation of EO2463 at the established dose in cohort 1 as monotherapy for 6 weeks and in combination with rituximab from week 7
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
15 Previously treated patients with FL Or MZL. Evaluation of EO2463 at the established dose in Cohort 1 in combination with lenalidomide and with addition of rituximab from week 19 onwards (depending on response)
Intervention Type
Biological
Intervention Name(s)
EO2463
Intervention Description
Multiple dose of EO2463
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
D1-21 of 4-weekly cycles
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
MabThera
Intervention Description
Multiple doses of rituximab
Primary Outcome Measure Information:
Title
Phase 1: Recommended Phase 2 Dose | Adverse Events Assessment |
Description
Incidences of adverse events, Treatment-Emergent Adverse events, Serious Adverse Events, Deaths, and Laboratory Abnormalities Using the National Cancer Institute-Common Terminology Criteria for Adverse events (NCI-CTCAE) V5.0.
Time Frame
Up to 24 months
Title
Phase 2: Overall Response Rate
Description
Overall Response Rate According to the Lugano Classification 2014 during EO2463 Monotherapy
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Safety and Tolerability for EO2463 Administered as Monotherapy and in Combination with Lenalidomide, Rituximab and Lenalidomide/Rituximab
Description
Incidences Of Adverse Events, Treatment-Emergent Adverse events, Serious Adverse events, Deaths, Treatment Discontinuations/Delays, And Laboratory Abnormalities Using The NCI-CTCAE V5.0 Grading System
Time Frame
Up to 24 months
Title
Assessment of the Immunogenicity in Relation to OMP72, OMP64, OMP65, OMP66, and UCP2 that Compose EO2463
Description
Immunogenicity will be assessed by interferon-Gamma (IFN-Γ) enzyme-Linked immunospot , and by intracellular cytokines staining, and multimers staining assays
Time Frame
Up to 24 months
Title
Overall Response Rate
Description
Overall Response Rate as described by the Lugano Classification 2014, and by the Lymphoma Response to Immunomodulatory Therapy Criteria (Lyric) 2016 by trial cohort
Time Frame
Up to 24 months
Title
Duration of response
Description
Duration of Response as described by the Lugano Classification 2014, and by the Lymphoma Response to Immunomodulatory Therapy Criteria (Lyric) 2016 by trial cohort
Time Frame
Up to 7 years after last patient enrolled
Title
Evaluation of Overall Survival
Description
The time interval from the date of first study treatment administration to the date of death due to any cause
Time Frame
Up to 7 years after last patient enrolled

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: For inclusion in Cohorts 1 and 4 patients should have relapsed/refractory, biopsy-proven grade 1, 2 or 3A, FL or MZL, ECOG performance status 0 to 2, and have received at least one prior line of treatment. For inclusion in Cohort 2 patients should have newly diagnosed, previously untreated (radiotherapy as only prior treatment is allowed), biopsy-proven grade 1, 2 or 3A, FL or MZL. ECOG performance status 0 or 1, and not be in need of standard of care therapy according to the assessment of the treating physician. Patients with only one prior treatment and a high-risk profile as defined by first progression of disease within 24 months of diagnosis (the exclusion is not applicable for patients with more than one prior line treatment). For inclusion in Cohort 3 patients should have newly diagnosed, previously untreated (radiotherapy as only prior treatment is allowed), biopsy-proven grade 1, 2 or 3A, FL or MZL. ECOG performance status 0 or 1, low tumor burden by Groupe d'Etude des Lymphomes Folliculaires criteria and be in need of therapy according to the assessment of the treating physician. Patients with an age ≥ 18 years old. Patients who are human leukocyte antigen (HLA)-A2 positive. Patients should have radiologically measurable disease with a lymph node or tumor mass greater than or equal to 1.5 cm in at least one dimension. Males or non-pregnant, non-lactating, females. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol. Patients having received the information sheet and who have provided written informed consent prior to any study-related procedures. Exclusion Criteria: Patients treated with dexamethasone > 2 mg/day or equivalent (i.e. 13 mg/day of prednisone, or 53 mg/day of hydrocortisone) within 14 days before the first EO2463 administration, unless required to treat an adverse event. Patients with grade 3B FL or transformation to an aggressive lymphoma subtype. Patients with only one prior treatment and a high-risk profile as defined by first progression of disease within 24 months of diagnosis (the exclusion is not applicable for patients with more than one prior line treatment). Patients with prior exposure to EO2463. Patients treated with immunotherapy (meaning immunostimulatory or immunosuppressive therapy; beside excluded, or allowed, compounds per other inclusion/exclusion criteria specifications), radionuclide therapy, radiotherapy, cytoreductive therapy, or received treatment with any other investigational agent within 28 days before the first EO2463 administration. Patients to be included in Cohorts 1 and 4, and who have received rituximab or other B cell ablation therapy within 8 weeks of start of study treatment. Patients with abnormal laboratory values. Patients with persistent Grade 3 or 4 toxicities. Uncontrolled central nervous system (CNS) metastasis. Other malignancy or prior malignancy with a disease-free interval of less than 3 years. Patients with clinically significant disease. Patients with suspected autoimmune or active autoimmune disorder or known history of an autoimmune neurologic condition (e.g. Guillain-Barré syndrome). Patients with history of solid organ transplantation or hematopoietic stem cell transplantation. Pregnant and breastfeeding patients. Patients with history or presence of human immunodeficiency virus and/or potentially active hepatitis B virus/hepatitis C virus infection.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jan Fagerberg, MD, PhD
Phone
+32 3 205 55 55
Email
medicalmonitoring-hem@enterome.com
First Name & Middle Initial & Last Name or Official Title & Degree
Karlijn Kroon, MD
Phone
+33 611300589
Email
kkroon-ext@enterome.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan Fagerberg, MD
Organizational Affiliation
Enterome
Official's Role
Study Director
Facility Information:
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Reid Merryman, Dr
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jose Caetano Villasboas Bisneto, Dr
Facility Name
University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center)
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonathan Friedberg, Dr
Facility Name
University of Washington-Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephen Smith, Dr
Facility Name
University of Bologna
City
Bologna
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
IRCCS Policlinico San Matteo Foundation - University of Pavia
City
Naples
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Pinto, Dr
Facility Name
IRCCS Policlinico San Matteo Foundation - University of Pavia
City
Pavia
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luca Arcaini, Dr
Facility Name
University Hospital Vall d'Hebron, Institute of Oncology
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francisco Bosch Albareda, Dr
Facility Name
Clinica Universidad de Navarra
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carlos Grande, Dr
Facility Name
Hospital Clinico Universitario de Salamanca
City
Salamanca
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ramon Garcia Sanz, Dr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma

We'll reach out to this number within 24 hrs