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

Paused · Phase 1

Conditions studied: Recurrent Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia

In brief

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.

Key facts

Study ID: NCT06447987
Run by: City of Hope Medical Center
People needed: 24
Starts: 2024-11-06
Expected to finish: 2026-12-05
Last updated by the study team: 2026-06-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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)
Creatinine clearance of ≥ 50 mL/min per 24-hour urine test or the Cockcroft-Gault formula
Left ventricular ejection fraction (LVEF) ≥ 45%
Note: To be performed within 28 days prior to start of protocol therapy
Cardiac function (12 lead-electrocardiogram [ECG]): Corrected QT interval (QTc) must be ≤ 480 msec
Oxygen (O2) saturation > 92% on room air
Note To be performed within 28 days prior to start of protocol therapy
Seronegative for HIV quantitative polymerase chain reaction (qPCR), hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR])
If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed. OR
If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. The viral load must be undetectable
Meets other institutional and federal requirements for infectious disease titer requirements

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
Females only: Pregnant or breastfeeding
Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of topical or inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone ≤ 7.5 mg /day or equivalent) is allowed
Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Where it is running

City of Hope Medical Center — Duarte, California, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.