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

NCT06343376 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: I-3641523NCI-2024-01818
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent High Grade B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Transformed Chronic Lymphocytic Leukemia; Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory High Grade B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Transformed Chronic Lymphocytic Leukemia; Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Will be graded on a scale of 1 to 5 as described by the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v 5.0).

  Up to 5 years

• Maximal tolerated dose (MTD) of EGFRt/19-28z/IL-12 chimeric antigen receptor T-cells

  Will be defined as the highest dose with an observed incidence of dose limiting toxicities in no more than one out of six patients treated at a particular dose level. Will be assessed using NCI CTCAE v 5.0.

  Within 30 days from the final infusion of the EGFRt/19-28z/IL-12 T cells

Secondary Outcomes (6)

• Incidence of complete remission (CR)/complete remission with incomplete count recovery (CRi)

  Within 3 months of CAR T-cell infusion

• Incidence of CR/CRi + partial response (PR) (ORR)

  Within 3 months of CAR T-cell infusion

• Event free survival

  Up to 5 years

• Overall survival

  Up to 5 years

• Progression-free survival

  Up to 5 years

Study Arms (2)

Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)

EXPERIMENTAL

Patients undergo leukapheresis prior to treatment. Patients 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.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Echocardiography; Biological: EGFRt/19-28z/IL-12 CAR T-lymphocytes; Procedure: Leukapheresis; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography

Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

EXPERIMENTAL

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.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography; Biological: EGFRt/19-28z/IL-12 CAR T-lymphocytes; Drug: Fludarabine Phosphate; Procedure: Leukapheresis; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography

Interventions

Biopsy PROCEDURE

Undergo tissue biopsy

Also known as: BIOPSY_TYPE, Bx

Cohort A (EGFRt/19- 28z/IL-12 CAR T cells); Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Cohort A (EGFRt/19- 28z/IL-12 CAR T cells); Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspiration

Cohort A (EGFRt/19- 28z/IL-12 CAR T cells); Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Cohort A (EGFRt/19- 28z/IL-12 CAR T cells); Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Cohort A (EGFRt/19- 28z/IL-12 CAR T cells); Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B-518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719, WR-138719

Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Cohort A (EGFRt/19- 28z/IL-12 CAR T cells); Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

EGFRt/19-28z/IL-12 CAR T-lymphocytes BIOLOGICAL

Given IV

Cohort A (EGFRt/19- 28z/IL-12 CAR T cells); Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Cohort A (EGFRt/19- 28z/IL-12 CAR T cells); Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Cohort A (EGFRt/19- 28z/IL-12 CAR T cells); Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Cohort A (EGFRt/19- 28z/IL-12 CAR T cells); Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with relapsed refractory B Cell malignancies which commonly express CD-19.
• Eligible disease subtypes include the following:
• Patients with diffuse large B-cell lymphoma (de novo or diffuse large B-cell lymphoma \[DLBCL\] transformed from an indolent lymphoma (follicular lymphoma, chronic lymphocytic leukemia) or high grade B-cell Lymphoma (HGBL):
• Relapsed or refractory DLBCL or high-grade B-cell lymphoma (HGBL) following 2 or more prior chemoimmunotherapy regimens containing an anthracycline and CD20-directed therapy following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma and requiring further treatment.
• Relapse following a single prior chemoimmunotherapy regimen containing an anthracycline and CD20-directed therapy following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma and considered ineligible for high dose chemotherapy and autologous stem cell rescue as determined by the investigator.
• Patients must have at least one fludeoxyglucose F-18 (FDG)-avid (PET-avid) measurable lesion.
• Biopsy confirmation of relapsed or refractory DLBCL is required.
• Chronic lymphocytic leukemia after 2 lines of therapy including a BTKi (bruton tyrosine kinase inhibitor).
• Mantle cell lymphoma after 2 lines of therapy. Patients must have previously received chemoimmunotherapy and a prior BTK inhibitor.
• Follicular lymphoma after 2 lines of therapy.
• For cohort 1A specifically, patients must additionally have received a prior CD19-targeted CAR T-cell therapy or not have an indication for a Food and Drug Administration (FDA)-approved commercial CD19-targeted CAR T-cell therapy. This will include patients with relapsed/refractory DLBCL, FL, CLL and MCL.
• For cohorts other than cohort 1A (and if needed, cohort -1), patients with an indication for an FDA approved commercial CD19-targeted CAR T-cell therapy are eligible following an informed consent discussion that reviews the risks and benefits of the FDA-approved commercial CD19-targeted CAR T-cell therapy vs the investigational product.
• Prior CD19-targeted therapies, including CAR T-cell therapy, does not exclude participation; however, CD19 expression by immunohistochemical staining or flow cytometry must be confirmed prior to enrollment for patients who have received such therapies.
• Age ≥ 18 years of age.
• Creatinine Clearance \> 30 mL/min (Cockroft-Gault equation).

You may not qualify if:

• Pregnant or lactating patients.
• Impaired cardiac function (left ventricular ejection fraction \[LVEF\] \< 40%) as assessed by ECHO or MUGA scan during screening.
• Patients with active graft versus host disease following allogeneic hematopoietic cell transplantation requiring systemic T cell suppressive therapy are ineligible.
• Patients with active autoimmune disease requiring systemic T cell suppressive therapy are ineligible.
• Patients with following cardiac conditions will be excluded:
• New York Heart Association (NYHA) stage III or IV congestive heart failure.
• Myocardial infarction ≤ 6 months prior to enrollment.
• Any history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration.
• Patients with HIV are ineligible.
• Patients with active hepatitis B infection (as manifest by either detectable hepatitis B virus deoxyribonucleic acid \[DNA\] by polymerase chain reaction \[PCR\] and/or positivity for hepatitis B surface antigen) are ineligible.
• Patients with active hepatitis C infection (as manifest by detectable hepatitis C virus ribonucleic acid \[RNA\] by PCR) are ineligible. Patients with detectable antibodies to hepatitis C virus will be screened by PCR for evidence of active infection.
• Patients with uncontrolled systemic fungal, bacterial, viral or other infection are ineligible.
• Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of skin.
• Patients with history or presence of clinically significant neurological disorders such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible.
• Patients with primary central nervous system (CNS) disease are ineligible.

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Interventions

Biopsy; Specimen Handling; Cyclophosphamide; fludarabine phosphate; Leukapheresis; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Francisco J Hernandez-ILizaliturri

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2024
• First Posted: April 2, 2024
• Study Start: November 26, 2024
• Primary Completion: January 3, 2025
• Study Completion: January 3, 2025
• Last Updated: August 3, 2025

Record last verified: 2025-07

Locations

US (1)