Humanized CD19-Specific CAR T Cells for the Treatment of Patients With Positive Relapsed or Refractory CD19 Positive B-Cell Acute Lymphoblastic Leukemia

NCT06447987 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 23328NCI-2024-03338P30CA033572
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial tests the safety, side effects, and effectiveness of humanized (hu)CD19-chimeric antigen receptor (CAR) T cell therapy in treating patients with CD19 positive B-cell acute lymphoblastic leukemia (ALL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). CAR T-cell therapy is a 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, such as CD19, 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 huCD19 positive CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Chemotherapy drugs, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. huCD19-CAR T cell therapy may be safe, tolerable and effective in treating patients with relapsed or refractory CD19 positive ALL.

Conditions

Recurrent Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  Toxicity/ adverse events will be graded using Common Terminology Criteria for Adverse Events version 5.0. Cytokine release syndrome and neurotoxicity will be graded using American Society for Transplantation and Cellular Therapy Consensus Criteria. Toxicity will be summarized and tabulated by count and percentage of subjects stratified by severity (grade), relatedness, terms or organ level.

  Up to 28 days after T cell infusion

Secondary Outcomes (11)

• Percentage of patients undergoing leukapheresis who get sufficient T cells manufactured and infused at assigned dose level

  At time of infusion

• Overall response rate (ORR)

  Up to 28 days post infusion

• Progression-free survival (PFS)

  From the start of CD-19 CAR T cell infusion to the date of death or disease progression/relapse, whichever occurring first, assessed up to 15 years

• Duration of response (DOR)

  From the start of CD19-CAR T cell infusion to the date of death or disease progression/relapse, whichever occurring first, assessed up to 15 years

• Overall survival (OS)

  From start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 15 years

Study Arms (1)

Treatment (huCD19-CAR T)

EXPERIMENTAL

Patients undergo leukapheresis then receive lymphodepletion chemotherapy with fludarabine IV and cyclophosphamide IV on days -5, -4 and -3 and huCD19-CAR T IV cells over 10-15 minutes on day 0. Patients may optionally receive cetuximab IV over 60-120 minutes at least 28 days post T cell infusion and undergo alloHCT. Additionally, patients undergo ECHO or MUGA, CT or PET/CT and optional MRI on study and bone marrow biopsy and aspiration and blood sample collection throughout the study.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Biological: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes; Biological: Cetuximab; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography; Drug: Fludarabine; Procedure: Leukapheresis; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo alloHCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (huCD19-CAR T)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (huCD19-CAR T)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspiration

Treatment (huCD19-CAR T)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

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

Treatment (huCD19-CAR T)

CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes BIOLOGICAL

Given IV

Also known as: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T Cells, CD19R(EQ)28zeta/EGFRt+ Naive and Memory T Cells, CD19R(EQ)28zetaEGFRt+ Tn/mem Cells

Treatment (huCD19-CAR T)

Cetuximab BIOLOGICAL

Given IV

Also known as: C225, Cetuximab Biosimilar CDP-1, Cetuximab Biosimilar CMAB009, Cetuximab Biosimilar KL 140, Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225

Treatment (huCD19-CAR T)

Computed Tomography PROCEDURE

Undergo CT and PET

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

Treatment (huCD19-CAR T)

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

Treatment (huCD19-CAR T)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (huCD19-CAR T)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (huCD19-CAR T)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (huCD19-CAR T)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (huCD19-CAR T)

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

Treatment (huCD19-CAR T)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

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

Treatment (huCD19-CAR T)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies.
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed. However, the research participant is allowed to proceed with lymphodepletion and T cell infusion only after the translated full consent form is signed
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) 0-2 / Karnofsky performance status (KPS) ≥ 70
• Histologically confirmed CD19+ relapsed/refractory ALL with at least 2 prior lines of therapy
• Prior alloHCT \> 100 days prior to enrollment may be considered a prior line of therapy
• Research participants with confirmed 1st or higher relapse of disease by morphology, cytogenetics or molecular, or research participants with refractory or residual disease
• Participants with central nervous system (CNS) involvement by leukemia (CNS2 and CNS3) may be considered eligible after discussions with the study team
• Patients with only MRD+ disease may be eligible
• Patients with isolated extramedullary disease may also be eligible
• Total bilirubin ≤ 2.0 X upper limit of normal (ULN) (unless has Gilbert's disease or related to leukemia involving the liver)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN (unless related to leukemia involving the liver)
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN (unless related to leukemia involving the liver)

You may not qualify if:

• Allogeneic stem cell transplant within 100 days at the time of enrollment
• Received prior CAR T therapy within 90 days of enrollment
• EXCEPTION: Participants who have previously received B-cell-activating factor receptor (BAFFR)-CAR T cells will be excluded from this study
• Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent(s)
• History or presence of clinically relevant CNS pathology such as uncontrolled seizure disorder, recent stroke, severe brain injuries, dementia, cerebellar disease or psychosis
• Autoimmune disease or active graft versus host disease (GVHD) requiring systemic immunosuppressant therapy
• Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification
• History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for ≥ 2 years
• Clinically significant uncontrolled illness
• Active systemic uncontrolled infection requiring antibiotics
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
• Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result. Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded
• Subjects who are hepatitis B core antibody positive (or have a known history of HBV infection) should be monitored quarterly with a quantitative PCR test for HBV deoxyribonucleic acid (DNA). HBV monitoring should last until 12 months after the last dose of study drug. Any subject with a rising viral load (above lower limit of detection) should discontinue study drug and have antiviral therapy instituted and a consultation with a physician with expertise in managing hepatitis B. Subjects who are core antibody (Ab) positive at study enrollment are strongly recommended to start Entecavir before start and until completion of study treatment
• Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Stem Cell Transplantation; Specimen Handling; Biopsy; Cetuximab; Cyclophosphamide; fludarabine; Leukapheresis; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Ibrahim Aldoss

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 9, 2024
• First Posted: June 7, 2024
• Study Start: November 6, 2024
• Primary Completion (Estimated): December 5, 2026
• Study Completion (Estimated): December 5, 2026
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

US (1)