Phase I Trial of IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
National Cancer Institute (NCI)
Summary
Background: Myeloid cells are a type of immune cell found in most tumors. Interleukin 12 (IL-12) is a protein that helps the immune system kill tumor cells. Researchers want to know if myeloid cells that have been genetically engineered to produce IL-12 (IL-12 GEMys) can activate the immune system to attack cancer cells in solid tumors. Objective: To test IL-12 GEMys in people with cancer. Eligibility People aged 18 years and older with cancer that returned or failed to respond to treatment. Design: Participants will be screened. They will have a physical exam with blood tests. They will have tests of their heart and lung function. They will have imaging scans of their tumors. A sample of tumor tissue may be taken. Participants will have daily injections for few days to prepare them to undergo leukapheresis: Blood will be taken from the body through a needle inserted into a vein. The blood will pass through a machine that separates out stem cells. The remaining blood will be returned to the body through a different needle. The collected stem cells will be modified in a lab to create IL-12 GEMys. Participants will check in to the hospital. They will receive drugs for 5 days to prepare their body for the treatment. Then they will have their own IL-12 GEMys infused through a needle inserted into a vein. They will stay in the hospital until they are well enough to go home. This may be 7 to 14 days or longer. Some participants may receive a second treatment with IL-12 GEMys within 2 years after the first. Participants will have follow-up visits for about 5 years. These will include imaging scans and blood tests.
Description
Background: * Myeloid cells are found in virtually all tumors, and they can play diverse roles in the tumor microenvironment including phagocytosing dying tumor cells, presenting antigen, suppressing anti-tumor immunity, and limiting natural killer (NK) and dendritic cell (DC) differentiation and function. * Hematopoietic stem and progenitor cells (HSPCs) and myeloid cells can be genetically modified to express cytokines, such as the anti-tumor cytokine interleukin (IL)-12, which can be delivered locally by recruited myeloid cells in tumor and metastatic tissues. * IL-12 is an important immun…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Relapsed or refractory solid tumor malignancies for whom standard measures do not exist or are no longer effective. Must have histologic confirmation of original diagnosis or relapse. * Participants must have evaluable (measurable or not measurable) disease. * Part B only: Participants must: * be willing to undergo mandatory pre- and post-treatment tumor biopsies. Tumor tissue should either be taken from non-target lesions or from target lesions where sampling can be done without impacting lesion measurement and --have disease amenable to biopsy to allow to perform…
Interventions
- BiologicalIL-12 GEMys
Cell therapy generated from autologous CD34+ cells. Administered on Day 0 as an IV infusion not to exceed 20ml/kg or 40ml/kg depending on DMSO levels.
- DrugCyclophosphamide
Lymphodepletive chemotherapy administered as 30 mg/kg IV infusion over 1 hour daily on days -6 and -5.
- DrugFludarabine
Lymphodeleptive chemotherapy administered as 25 mg/m\^2 IV infusion over 30 minutes on days -6 through -2.
- DrugCetuximab
Administered as IV infusion at 500 mg/m\^2, if needed.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland