Health Trials

IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors

ConditionsRelapsed Solid Tumor MalignanciesRefractory Solid Tumor Malignancies
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-120
SponsorNational Cancer Institute (NCI)

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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

Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy and close monitoring for over 3 months shows no active progression.

Disqualifiers

Participants with history of primary CNS tumors or leptomeningeal disease.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, IL-12, or other agents used in the study.

Concurrent untreated opportunistic infections as evidenced by history, blood test or imaging at screening.

Active systemic infections requiring anti-infective treatment.

Trial design

Design model

Sequential

Treatments tested in this trial

  • IL-12 GEMys

    Biological/Vaccine

    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.

  • Cyclophosphamide

    Drug

    Lymphodepletive chemotherapy administered as 30 mg/kg IV infusion over 1 hour daily on days -6 and -5.

  • Fludarabine

    Drug

    Lymphodeleptive chemotherapy administered as 25 mg/m\^2 IV infusion over 30 minutes on days -6 through -2.

  • Cetuximab

    Drug

    Administered as IV infusion at 500 mg/m\^2, if needed.

Treatment groups

95 Participants
are divided into 2 treatment groups
Group A: Arm 1Experimental treatment 4 interventions
Group B: Arm 2Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Part A (Escalation): Determine the recommended phase 2 dose (RP2D) of IL-12

Maximum dosage of GEMys IL-12 with which no more than 1 participant experience dose limiting toxicity as assessed by grade of adverse event

Time frame
0-28 Days
2

Part B (Expansion): Assess whether IL-12 or IFNy levels, or both increase in tumors post treatment at the RP2D

Increased IL-12 and/or IFNy levels and IL-12 production as measured by ELISA, using a paired t-test or Wilcoxon signed rank test

Time frame
1 week

Secondary outcomes

1

Determine the feasibility of manufacturing IL-12 GEMys that express a truncated epidermal growth factor receptor (EGFRt) meeting release criteria

Number of participants at each dose level for whom the target number of cells at that dose level can be manufactured and assessed prior to infusion

Time frame
Time of cell infusion
2

Determine the safety of IL-12 GEMys

Safety data will be analyzed per standard methods and interpreted descriptively for each dose level. Ongoing analysis of toxicity using CTCAE and RCL collected from the blood

Time frame
0-12 months
3

Assess the antitumor activity of IL-12 GEMys

Overall response rate (ORR) (PR + CR) per RECIST 1.1

Time frame
0-5 years
4

Assess the re-treatment utility of IL-12 GEMys

Assessment of clinical response per RECIST

Time frame
0-5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: