Sequential Intranodal Immunotherapy (SIIT) Combined With Anti-PD1 (Pembrolizumab) in Follicular Lymphoma

NCT02677155 | Completed Phase 2 DMC

• 1 other identifier: Lymvac-2
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin's lymphoma and is often diagnosed in advanced incurable stage. In our previous trail, Lymvac-1, patients were treated with sequential intratumoral injections of low-dose rituximab and autologous dendritic cells, combined with local radiotherapy at the same site. The aim was to overcome tumor tolerance. In this trial, clinical responses correlated strongly with systemic anti-tumor CD8+ T-cell responses detected in blood after therapy. The primary aim of the planned study (Lymvac-2) is to significantly improve rates of immunological and clinical responses by adding iv anti-PD-1 antibody (Pembrolizumab) relative to the cohort of patients previously treated with intranodal immunotherapy without Pembrolizumab (Lymvac-1). The study includes 10 patients with untreated or relapsed FL.

Conditions

Follicular Lymphoma

Keywords

Follicular lymphoma; Intranodal therapy; Autologous dendritic cells; Rituximab; Immunotherapy; Cancer vaccine; Anti-PD1; Pembrolizumab; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Change in tumor load from baseline until maximal regression

  Evaluated at baseline, 2, 4, 8, 12 and 24 months

Secondary Outcomes (7)

• Duration of response

  From date of documented response until progression, assessed up to 60 months

• Progression-free survival

  From date of inclusion until date of documented progression or death of any cause, whichever came first, assessed up to 60 months

• Time to next treatment

  From date of inclusion until start of next treatment, assessed up to 60 months

• Overall survival

  From date of inclusion until death of any cause, assessed up to 60 months

• Change in total tumor volume

  Compared assessments at inclusion and at time of best response, as assessed up to 60 months, an average of 12 months

Study Arms (1)

Intranodal immunotherapy and anti-PD1

EXPERIMENTAL

Induction phase: 3 cycles of sequential intranodal immunotherapy (SIIT), every second week: Radiotherapy 8 Gy single dose day 2, Rituximab 5 mg intranodal day 1 and 3, Autologous dendritic cells 1x 10 e8 intranodal day 4 and 5, GM-CSF 50 ug subcutaneously day 4 and 5, Pembrolizumab 200 mg intravenous day 5, Consolidation phase: Pembrolizumab 200 mg intravenous every third week for 8 cycles

Radiation: Radiotherapy; Biological: Rituximab; Biological: Autologous dendritic cells; Biological: GM-CSF; Biological: Pembrolizumab

Interventions

Radiotherapy RADIATION

Radiotherapy 8 Gy single dose

Intranodal immunotherapy and anti-PD1

Rituximab BIOLOGICAL

Intranodal injection 5 mg

Also known as: Mabthera

Intranodal immunotherapy and anti-PD1

Autologous dendritic cells BIOLOGICAL

Intranodal injection of 1 x 10 e8 cells

Intranodal immunotherapy and anti-PD1

GM-CSF BIOLOGICAL

Subcutaneous injection of 50 ug

Also known as: Sagramostim

Intranodal immunotherapy and anti-PD1

Pembrolizumab BIOLOGICAL

Intravenous infusion of 200 mg

Also known as: Anti-PD1

Intranodal immunotherapy and anti-PD1

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be \>= 18 years of age on day of signing informed consent.
• Histologically confirmed incurable asymptomatic untreated or relapsed follicular lymphoma grade I-IIIA stage III-IV
• Lymphoma nodes greater than 1.5 cm at sites suitable for radiation and ultrasound-guided injections
• Have measurable disease outside irradiated sites.
• Be willing to provide tissue from an excisional biopsy of a tumor lesion
• Have a performance status of 0 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined below. Absolute neutrophil count (ANC) \>=1,500 /mcL, Platelets \>=100,000 / mcL, Hemoglobin \>=9 g/dL, Serum creatinine \>=1.5 X upper limit of normal (ULN) Serum total bilirubin \>= 1.5 X ULN. AST (SGOT) and ALT (SGPT) \>= 2.5 X ULN OR \>= 5 X ULN for subjects with liver metastases, Albumin \>=2.5 mg/dL International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) \>=1.5 X ULN
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Has progressive lymphoma in need of standard therapy
• Has transformation to more aggressive disease like diffuse large B cell lymphoma
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to rituximab, GM-CSF, pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Oslo University Hospital: lead
• Norwegian Cancer Society: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Oslo University Hospital Radiumhospitalet

Oslo, 0310, Norway

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Radiotherapy; Rituximab; Granulocyte-Macrophage Colony-Stimulating Factor; Colony-Stimulating Factors; pembrolizumab; spartalizumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Arne Kolstad, MD PhD

  Dept of Oncology, Oslo University Hospital Radiumhospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: February 2, 2016
• First Posted: February 9, 2016
• Study Start: January 1, 2016
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: March 1, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After 5 year follow-up
• Access Criteria: Collaborating researchers on demand

Locations

NO (1)