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Follicular LymphomaPhase 2Lymvac-2NCT02677155

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

A Phase 2 study testing Radiotherapy, Rituximab and Autologous dendritic cells in people with Follicular Lymphoma, run by Oslo University Hospital at 1 site in Norway.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Follicular Lymphoma
What is being tested?
Radiotherapy, Rituximab and Autologous dendritic cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteNorway
Study dates
Jan 2016to Feb 2021
Phase
Phase 2
Are there results?
None posted in the registry

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

  • 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
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy.

Trial locations and contacts

1 site in 1 country.

Norway1 site

  • Oslo University Hospital Radiumhospitalet

    Oslo, 0310

Other trials in Norway

About this study

Official title: Open Label, Phase II, Study: Sequential Intranodal Immunotherapy (SIIT) Combined With Anti-PD1 (Pembrolizumab) in Patients With Stage III/IV Untreated and Relapsed Follicular Lymphoma

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.

Read the detailed description

Patients with advanced stage follicular lymphoma, untreated and relapsed are eligible for this study. Staging includes PET/CT, CT and bone marrow specimens. Lymphoma nodes must be available for surgical biopsy, radiation and intranodal treatment. Additionally, there must be evaluable lesions for measuring systemic effects. The patient undergo leukapheresis for collection of monocytes then cultured ex vivo to obtain immature dendritic cells (DC). The treatment targets single lymphoma nodes with radiation (single fraction of 8 Gy), ultrasound-guided injections of autologous DCs , low-dose rituximab (5 mg) and GM-CSF sc. This sequential intranodal immunotherapy (SIIT) is repeated three times, targeting different lymphoma nodes. Anti-PD1 monoclonal antibody (Pembrolizumab) is given iv at each cycle of SIIT and then every third week for a total of 11 cycles. Patients are evaluated for clinical response with PET/CT, CT and bone marrow analysis. CD8 and CD4 T cell responses against autologous tumor cells are measured in blood after treatment by flow cytometry. The primary aims are to induce systemic clinical responses and correlated T cell responses which may prolong time to next standard therapy.

Being tested
Radiotherapy, Rituximab, Autologous dendritic cells, GM-CSF, Pembrolizumab
Keywords
Follicular lymphoma, Intranodal therapy, Autologous dendritic cells, Rituximab, Immunotherapy, Cancer vaccine, Anti-PD1, Pembrolizumab, Radiotherapy
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RadiotherapyRadiation

    Radiotherapy 8 Gy single dose

  • RituximabBiological

    Also called Mabthera

    Intranodal injection 5 mg

  • Autologous dendritic cellsBiological

    Intranodal injection of 1 x 10 e8 cells

  • GM-CSFBiological

    Also called Sagramostim

    Subcutaneous injection of 50 ug

  • PembrolizumabBiological

    Also called Anti-PD1

    Intravenous infusion of 200 mg

Study groups in NCT02677155
Study groupRoleWhat they receive
Intranodal immunotherapy and anti-PD1ExperimentalInduction 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
Receives: Radiation: Radiotherapy; Biological: Rituximab; Biological: Autologous dendritic cells; Biological: GM-CSF; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate

    Change in tumor load from baseline until maximal regression

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

Secondary outcomes (7)

  1. Duration of response

    DOR

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

  2. Progression-free survival

    PFS

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

  3. Time to next treatment

    TNT

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

  4. Overall survival

    OS

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

  5. Change in total tumor volume

    cTTV

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

  6. Safety: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Measured: From inclusion, assessed up to 60 months

  7. Anti-tumor T cell responses in blood

    T-cell proliferation

    Measured: Assessed at inclusion and up to 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Feb 2016 (estimated)
  2. Study startJan 2016
  3. Primary completionFeb 2021
  4. Study completionFeb 2021

Resources

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
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02677155
Sponsor's protocol ID
Lymvac-2
Acronym
Lymvac-2
Status last verified
Feb 2021
First submitted
2 Feb 2016
Last updated
1 Mar 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: Shared when study is published

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Radiotherapy, Rituximab and Autologous dendritic cells in people with Follicular Lymphoma, run by Oslo University Hospital at 1 site in Norway.

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 11 inclusion and 22 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: finished, as of the sponsor's last update on 1 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Norway. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Overall response rate (time frame: Evaluated at baseline, 2, 4, 8, 12 and 24 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 NCT02677155.

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 1 Mar 2021.

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