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Trials / Terminated

TerminatedNCT06343376

Genetically Engineered Cells (EGFRt/19-28z/IL-12 CAR T Cells) for the Treatment of Relapsed or Refractory CD19+ Hematologic Malignancies

A Phase I Trial of CD19-Targeted Chimeric Antigen Receptor (CAR) Modified T Cells Genetically Engineered to Secrete Interleukin 12 (IL-12) and With a Truncated Human Epidermal Growth Factor Receptor (EGFRt) in Patients With Relapsed or Refractory CD19+ Hematologic Malignancies

Status
Terminated
Phase
Phase 1
Study type
Interventional
Enrollment
1 (actual)
Sponsor
Roswell Park Cancer Institute · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of genetically engineered cells called EGFRt/19-28z/IL-12 CAR T cells, and to see how they work in treating patients with hematologic malignancies that makes a protein called CD19 (CD19-positive) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Chimeric Antigen Receptor (CAR) T-cell Therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. To improve the effectiveness of the modified T cells and to help the immune system fight cancer cells better, the modified T cells given in this study will include a gene that makes the T cells produce a cytokine (a molecule involved in signaling within the immune system) called interleukin-12 (IL-12). The researchers think that IL-12 may improve the effectiveness of the modified T cells, and it may also strengthen the immune system to fight cancer. Giving EGFRt/19-28z/IL-12 CAR T cells may be safe and tolerable in treating patients with relapsed or refractory CD19+ hematologic malignancies.

Detailed description

PRIMARY OBJECTIVE: I. To determine the safety, toxicity and maximum tolerated dose (MTD) of EGFRt/19-28z/IL-12 CAR T-lymphocytes (EGFRt/19-28z/IL-12 CAR T cells) in patients with relapsed or refractory CD19+ aggressive hematologic malignancies. SECONDARY OBJECTIVES: I. To assess the anti-tumor efficacy of adoptively transferred EGFRt/19-28z/IL-12 T cells. II. To assess the in vivo persistence of adoptively transferred EGFRt/19-28z/IL-12 T cells. EXPLORATORY OBJECTIVES: I. To describe the cellular and cytokine microenvironment following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells. II. To characterize endogenous anti-tumor immune responses following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells. III. To summarize levels of normal B cells and the incidence of B cell aplasia following infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells. IV. To determine the proportion of evaluable patients who achieve minimal residual disease (MRD)-negativity in peripheral blood and/or bone marrow. V. To assess phenotype and in vitro function of end-of-production (EOP) EGFRt/19-28z/IL-12 CAR T cells and phenotype at recovery following CAR T cell administration. OUTLINE: This is a dose-escalation study of EGFRt/19- 28z/IL-12 CAR T cells. Patients are assigned to 1 of 2 cohorts. COHORT A: Patients undergo leukapheresis prior to treatment. Patients receive EGFRt/19- 28z/IL-12 CAR T cells intravenously (IV) over 5 to 30 minutes on day 0. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo computed tomography (CT) or positron emission tomography (PET) as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial. COHORT B: Patients undergo leukapheresis prior to treatment and receive lymphodepletion chemotherapy with cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on days -5, -4, and -3. Patients then receive EGFRt/19- 28z/IL-12 CAR T cells IV over 5 to 30 minutes on day 0. Patients also undergo ECHO or MUGA during screening. Patients also undergo CT or PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial. After completion of study treatment, patients are followed up weekly for 4 weeks, every 4 weeks until 24 months, every 3 months thereafter for 1 year, then annually for up to 5 years, followed by long-term follow up for up to 15 years.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiopsyUndergo tissue biopsy
PROCEDUREBiospecimen CollectionUndergo blood sample collection
PROCEDUREBone Marrow AspirationUndergo bone marrow biopsy and aspiration
PROCEDUREBone Marrow BiopsyUndergo bone marrow biopsy and aspiration
PROCEDUREComputed TomographyUndergo CT
DRUGCyclophosphamideGiven IV
PROCEDUREEchocardiographyUndergo ECHO
BIOLOGICALEGFRt/19-28z/IL-12 CAR T-lymphocytesGiven IV
DRUGFludarabine PhosphateGiven IV
PROCEDURELeukapheresisUndergo leukapheresis
PROCEDUREMultigated Acquisition ScanUndergo MUGA
PROCEDUREPositron Emission TomographyUndergo PET

Timeline

Start date
2024-11-26
Primary completion
2025-01-03
Completion
2025-01-03
First posted
2024-04-02
Last updated
2025-08-03

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT06343376. Inclusion in this directory is not an endorsement.