Follicular Lymphoma
Conditions
Keywords
Follicular Lymphoma
Brief summary
This research study is studying a novel type of FL vaccine as a possible treatment for follicular lymphoma (FL). The agents involved in this study are: * Rituximab * Personalized NeoAntigen vaccine * Poly-ICLC * Pembrolizumab
Detailed description
This research study is a Pilot Study, which is the first time investigators are examining the Personalized Neoantigen Vaccine (NeoVax) in patients diagnosed with follicular lymphoma. The FDA (the U.S. Food and Drug Administration) has not approved the Personalized Neoantigen Vaccine as a treatment for any disease. Patients will receive 4 weekly doses rituximab (a CD20 monoclonal antibody) during NeoVax manufacturing (see below). Patients who have stable disease or achieve a response with rituximab therapy will next receiving NeoVax alone (first 5 patients) or NeoVax in combination with pembrolizumab (a PD-1 monoclonal antibody). The purpose of this study is to determine if it is possible to make and safely administer a vaccine against FL by using information gained from specific genetic characteristics of the participant's own FL cells. The investigators plan to analyze the specific genetic characteristics of the participant's own FL cells and use that information to produce proteins that may help the participant's immune system recognize and fight FL cells. This vaccine has already been tested in clinical trials in patients with advanced melanoma (a type of skin cancer) and glioblastoma (a type of brain cancer). The current study will examine the ability of the vaccine to stimulate the participant's immune system when given at several different timepoints, and will examine the participant's blood cells for signs that the FL has changed or decreased. FL cells will be obtained from a tumor biopsy. The genetic material contained in the FL cells will be examined for the presence of tumor-specific mutations. This information will be used to prepare small protein fragments, which are called "peptides." The vaccine will consist of up to 20 of these peptides as well as a drug called Poly-ICLC. A peptide from the tetanus vaccine will also be included to boost the immune response. Poly-ICLC (also called Hiltonol) is an experimental "viral mimic" and an activator of immunity. Poly-ICLC binds proteins on the surface of certain immune cells to make it appear as if a virus is present. When the cells detect the vaccine, they think it is a virus and turn on the immune system. Poly-ICLC will be mixed with NeoAntigen peptides and administered as an injection given underneath the skin. Poly-ICLC is an investigational drug, meaning the FDA has not approved it as a treatment for any disease.
Interventions
DRUGRituximab
Rituximab is classified as a monoclonal antibody. It works by targeting the CD20 antigen on normal and malignant B-cells. Then the body's natural immune defenses are recruited to attack and kill the marked B-cells
BIOLOGICALNeo Vax
Neo Vax is an experimental "viral mimic" and an activator of immunity.
DRUGPembrolizumab
Pembrolizumab is a monoclonal antibody that targets PD-1. It is a type of immunotherapy
Sponsors
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All patients will receive 4 weekly doses of rituximab. Afterwards, will receive either NeoVax alone (first 5 patients) or NeoVax in combination with pembrolizumab (5 patients)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of grade I-IIIA follicular lymphoma (pathology must be confirmed at DFCI/BWH) * Planned treatment with 4 weekly doses of rituximab. * No prior systemic therapy for follicular lymphoma; prior radiation with palliative or curative intent is allowed if radiation occurred more than 3 months prior to study entry * Patient must have measurable disease by Cheson criteria * Age ≥ 18 years. * ECOG performance status \< 2. * Participants must have normal organ and marrow function as defined below: * Hemoglobin \> 9 gm/dl (ESAs or transfusion are not allowed) \[greater than 8 gm/dl if there is lymphoma involvement of the bone marrow\] * ANC \> 1000 (greater than 750 if there is lymphoma involvement of the bone marrow) * Platelet count \>100,000 (greater than 50,000 if there is lymphoma involvement of the bone marrow\] * International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) \< 1.5 x ULN unless subject is on anticoagulation as long as PT or aPTT is within intended therapeutic range of anticoagulant used * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal (\< 5 x ULN if there are hepatic metastases) * Creatinine \< 1.5 x ULN or measured or calculated creatinine clearance (GFR can also be used in place of creatinine clearance) \> 30 ml/min for subject with creatinine \> 1.5 x institutional ULN * total bilirubin less than institutional 1.5 x ULN (or a direct bilirubin \< ULN if total bilirubin is \>1.5 x ULN) * The effects of NeoVax and poly-ICLC on the developing human fetus are unknown. For this reason, women of childbearing potential (WOCBP) must have a negative pregnancy test (serum) before entry onto the trial and within 7 days prior to start of study vaccination. * Female patients enrolled in the study, who are not free from menses for \>2 years, post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity throughout the study, starting with visit 1 through 4 weeks after the last dose of study therapy. Approved contraceptive methods include for example; intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception. Male participants need to agree to use an adequate method of contraception * Patient is agreeable to allow tumor (from peripheral blood, lymph node, or effusion) and normal tissue (from saliva) samples to be submitted for complete exome and transcriptome sequencing. * Ability to understand and the willingness to sign a written informed consent document. Additional Inclusion Criteria for Treatment Registration * Participants must meet the following criteria (in addition to the above) to be eligible to proceed to receive vaccine treatment on the study: * At least 7 immunizing peptides can be designed * Continue to meet inclusion and
Exclusion criteria
for Screening Registration (note: hepatitis B and hepatitis C serologies do not need to be repeated unless there is a clinical concern that an exposure has occurred since the screening phase). * Achieved a CR, PR, or SD with no residual mass greater than 5 cm per Lugano criteria following single agent rituximab per
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Neovax following 4 weekly doses of rituximab assessed by the following | 2 years | The proportion of all enrolled patients for whom sequencing and analysis leads to identification of at least 7 actionable peptides to initiate vaccine production and, of the patients who generate at least 7 actionable peptides, the proportion for whom the time from sample collection to vaccine availability is less than 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of participants who achieve an IFN-γ T cell response to one or more of the peptide pools | 2 years | The induction of IFN-γ T-cell response will be based on ELISPOT assessments taken prior to vaccine administration and at week 16 from both peripheral blood draws and bone marrow biopsies. The proportion of patients who achieve more than 55 SFU/106 PBMC or 3 times their baseline level will be presented with a 90% exact binomial confidence interval. Based on a cohort of size 10, the confidence interval will be no wider than 0.55. It is possible that the maximal response will occur at a different sampling time point or will vary between participants. Thus, this time point may vary from week 16. |
| The proportion of participants who convert from PR to CR | 2 years | The investigators will report the proportion of patients converting from SD to CR/PR or from PR to CR based upon Lugano criteria in a descriptive fashion. |
| The proportion of participants who convert from SD to PR/CR | 2 years | The investigators will report the proportion of patients converting from SD to CR/PR or from SD to PR or CR based upon Lugano criteria in a descriptive fashion. |
| Best Objective Response | 2 years | The investigators will report the best objective response (CR, PR, SD, or PD) based upon Lugano criteria in a descriptive fashion. |
| To describe the safety and tolerability of NeoVax following 4 weekly doses of rituximab in patient with previously untreated follicular lymphoma | 2 years | The investigators will report toxicity in a descriptive fashion using CTCAE version 4.0 |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORReid W Merryman, MD
Dana-Farber Cancer Institute
Outcome results
None listed