Allogeneic CMV-Specific CD19-CAR T Cells Plus CMV-MVA Triplex Vaccine After Matched Related Donor Hematopoietic Cell Transplant for the Treatment of Patients With High-Risk Acute Lymphoblastic Leukemia

Recruiting now · Early Phase 1

Conditions studied: Acute Lymphoblastic Leukemia

In brief

This early phase I trial tests the safety and side effects of allogeneic CMV-specific CD19-CAR T cells plus CMV-MVA vaccine and how well it works in treating patients with high-risk acute lymphoblastic leukemia after a matched related donor (allogeneic) hematopoietic stem cell transplant (alloHSCT). Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which 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, in this study, the T cells are cytomegalovirus (CMV) specific. Then the gene for a special receptor that binds to a certain protein, CD19, on the patient's cancer cells is added to the CMV-specific T cells in the laboratory. The special receptor is called a 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. Vaccines made from three CMV tumor associated antigens, may help the body build an effective immune response to kill cancer cells. Giving allogeneic CMV-specific CD19-CAR T cells plus CMV-MVA vaccine after matched related alloHSCT may be safe, tolerable, and/or effective in treating patients with high-risk acute lymphoblastic leukemia.

Key facts

Study ID

NCT06735690

Run by

City of Hope Medical Center

People needed

15

Starts

2025-12-30

Expected to finish

2029-03-07

Last updated by the study team

2026-04-27

Who can join

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

You may qualify if…

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study 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
• Age: ≥ 18 years
• Karnofsky performance status (KPS) ≥ 70
• Participants with high-risk ALL defined as:
• Any complete remission (CR) with minimal residual disease (MRD)+ (by flow cytometry, polymerase chain reaction [PCR] or clonoSEQ) at the time of HSCT; or
• Blasts ≥ 5% at the time of transplant; or
• Complete response (CR)2 or higher irrespective of MRD status; or
• Requiring > 1 regimen to achieve CR1
• Pathology confirmed CD19+ ALL after the last targeted therapy if the patient has active disease or before the last therapy if the patient is in CR
• Note: CD19 positivity must be documented in a pathology report; however, it is not a requirement that the CD19 testing be performed by a COH pathologist
• Planned allogeneic HSCT (myeloablative or reduced intensity conditioning) according to institutional eligibility requirements with an available 8/8 (HLA A, B, C, DR) allele-matched related is allowed per discretion of the principal investigator. for allogeneic HSCT will be unmanipulated mobilized peripheral blood stem cell (PBSC) or bone marrow
• Participants who received other prior forms of CAR T therapy are eligible
• No known contraindications to HSCT, leukapheresis, steroids or tocilizum,ab, smallpox vaccine and any other modified vaccinia ankara virus (MVA)-based vaccines
• Total serum bilirubin ≤ 2.0 mg/dL (to be performed no more than 45-days prior to hematopoeitic stem cell [HSC] infusion unless otherwise stated)
• Participants with Gilbert syndrome may be included if their total bilirubin is ≤ 3.0 (to be performed no more than 45-days prior to HSC infusion unless otherwise stated)
• Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN) (to be performed no more than 45-days prior to HSC infusion unless otherwise stated)
• Alanine aminotransferase < 2.5 x ULN (to be performed no more than 45-days prior to HSC infusion unless otherwise stated)
• Serum creatinine ≤ 2.5 x ULN or estimated creatinine clearance of ≥ 40 mL/min per the Cockcroft-Gault formula, and the participant is not on hemodialysis (to be performed no more than 45-days prior to HSC infusion unless otherwise stated)
• Cardiac function (12 lead-electrocardiogram [ECG]): Corrected QT interval (QTc) must be ≤ 480 msec (to be performed no more than 45-days prior to HSC infusion unless otherwise stated)
• Left ventricular ejection fraction ≥ 45% within 8 weeks before protocol therapy (to be performed no more than 45-days prior to HSC infusion unless otherwise stated)
• Oxygen (O2) saturation > 92% without requiring supplemental oxygen (to be performed no more than 45-days prior to HSC infusion unless otherwise stated)

You may not qualify if…

• Concurrent use of systemic steroids. Recent or current use of inhaled or topical steroids in standard doses is not exclusionary. Physiologic replacement of steroids (prednisone ≤ 0.5 mg /day, or equivalent doses of other corticosteroids) is allowed
• Participants with active autoimmune disease requiring systemic immune suppressive therapy are not allowed
• Any contraindications to standard conditioning transplant regimens per standard of care practices at COH
• Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening
• History or prior diagnosis of other immunologic or inflammatory disease affecting the central nervous system (CNS), including uncontrolled seizure disorder, any measurable masses of CNS, or any other active CNS disease. Note: Research participants with a history of CNS disease that has been effectively treated to complete remission (< 5 white blood cells [WBC]/mm\^3 and no blasts in CSF) will be eligible
• Participants should not have any uncontrolled illness including symptomatic congestive heart failure, unstable angina pectoris, poorly controlled pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• History of stroke or intracranial hemorrhage within 3 months prior to screening
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
• Participants with uncontrolled seizures
• Active viral hepatitis
• 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 infection not responding to antibiotics
• Females only: Pregnant or breastfeeding
• 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 (enrolling)

Full record on ClinicalTrials.gov

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