Lymphocytic Leukemia
Conditions
Keywords
Leukemia, Lymphocytic Leukemia
Brief summary
This research study is studying a novel type of CLL vaccine as a possible treatment for chronic lymphocytic leukemia (CLL) The names of the study interventions involved in this study are: * Personalized NeoAntigen Vaccine * Poly-ICLC * Cyclophosphamide * Pembrolizumab
Detailed description
This research study evaluates the feasibility and tolerability of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. Investigational means that the intervention is being studied and that research doctors are trying to find more about it. It also means that the FDA (US Food and Drug Administration) has not approved the Personalized Neoantigen Cancer Vaccine for any use in patients, including people with CLL. This is the first time NeoVax vaccine will be given in combination with cyclophosphamide and Pembrolizumab in humans. The purpose of this study is to determine if it is possible to make and safely administer a vaccine against CLL. The investigators plan to analyze the specific genetic characteristics (mutations) of the participant's own CLL and use that information to produce proteins that may help the immune system recognize and fight CLL cells. This vaccine is also being tested in clinical trials in patients with advanced melanoma (a type of skin cancer) or glioblastoma (a type of brain cancer). The current study will examine the ability of the vaccine to stimulate the immune system when given at several different timepoints, and will examine the participant blood cells for signs that the CLL has changed or decreased. CLL cells will be obtained from bone marrow biopsy and blood draws. The genetic material contained in the CLL 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 may also be included to boost the immune response. A third of the patients enrolled in this trial will receive the personalized neoantigen vaccine. Another third of the patients will also receive low doses of a chemotherapy drug called cyclophosphamide in combination of personalized neoantigen vaccine. The last third of patients enrolled in this study will receive the personalized neoantigen vaccine in combination with low dose cyclophosphamide and a drug called Pembrolizumab. 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. Cyclophosphamide (also called Cytoxan) is a chemotherapy drug used to treat many cancers, including CLL. At the much lower dose used in this study, it is an investigational drug to help the immune cells to be better at attacking cancer cells. Pembrolizumab is a monoclonal antibody used to treat other types of cancer and information from these studies suggests that it may be beneficial in CLL.
Interventions
DRUGNeoVax
It stimulates the immune system to attack cancer cells.
DRUGCyclophosphamide
It is a chemotherapy drug used to treat many cancers. At low doses, it is an investigational drug to help the immune cells to be better at attacking cancer cells while avoiding chemotherapy toxicity.
DRUGPembrolizumab
Is a monoclonal antibody that helps the immune cells to be better at attacking cancer cells.
Sponsors
Oncovir, Inc.
BioNTech SE
Merck Sharp & Dohme LLC
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of CLL as per IWCLL 2018 criteria * Patient's CLL must have an unmutated immunoglobulin heavy chain variable (IGHV) region gene, defined as \< 2% mutated compared to germline. * Patient must have had no history of CLL-directed therapy due to meeting IWCLL 2018 criteria; no present indication for treatment by iwCLL 2018 criteria; and in the opinion of the treating investigator be anticipated not to require CLL-directed treatment within the next 6 months. * Patient must have measurable disease (absolute lymphocyte count \> 10K/uL or total white blood cell count ≥ 20K/uL of peripheral blood). * Patient must have had at least two other absolute lymphocyte counts (ALC) measured since diagnosis of CLL that are at least 2 weeks apart and at least 2 months prior to the one used for initial registration. * Age ≥ 18 years. * ECOG performance status 0 or 1 * Participants must have normal organ and marrow function as defined below: * total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal * absolute neutrophil count ≥1000 cells/μL * 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 (minimum sensitivity 25 IU/L or equivalent of HCG) before entry onto the trial and within 7 days prior to start of study medication. It is the investigators' responsibility to repeat the pregnancy test should start of treatment be delayed. * 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. * Patient is agreeable to allow tumor (from peripheral blood) 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. * At least 7 immunizing peptides can be designed. * Continue to meet inclusion and
Exclusion criteria
for Screening Registration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of neoantigen identification | 6 months | The proportion of all enrolled patients for whom sequencing and analysis leads to identification of at least 7 actionable peptides to initiate vaccine production |
| Feasibility of vaccine generation | 6 months | 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 |
| Safety of NeoVax | 1 year | The number of patients with treatment-limiting toxicities based on NCI CTCAE v5.0 |
Countries
United States
Contacts
Primary ContactOriol Olive Noguer
Outcome results
None listed