NCT03219450

A Personalized Neoantigen Cancer Vaccine in Treatment Naïve, Asymptomatic Patients With IGHV Unmutated CLL.

A Pilot Study of a Personalized Neoantigen Cancer Vaccine With and Without Low-Dose Cyclophosphamide or Pembrolizumab in Treatment Naïve, Asymptomatic Patients With IGHV Unmutated Chronic Lymphocytic Leukemia.

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Dana-Farber Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Lymphocytic Leukemia

Interventions

Type	Name	Description
DRUG	NeoVax	It stimulates the immune system to attack cancer cells.
DRUG	Cyclophosphamide	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.
DRUG	Pembrolizumab	Is a monoclonal antibody that helps the immune cells to be better at attacking cancer cells.

Timeline

• Start date: 2021-08-18
• Primary completion: 2027-05-31
• Completion: 2028-03-31
• First posted: 2017-07-17
• Last updated: 2025-05-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study