CAR T-Cell Therapy and Vaccine for Acute Lymphoblastic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: City of Hope Medical Center

Must not be taking: Systemic steroids

Disqualifiers: Autoimmune disease, CNS disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 21

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Who Is on the Research Team?

Ibrahim Aldoss, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for high-risk acute lymphoblastic leukemia patients who have undergone a stem cell transplant from a matched related donor. Participants must be eligible for all study procedures and interventions.

Inclusion Criteria

Negative for COVID-19 within 72 hours of day 0 of protocol therapy

Participants with Gilbert syndrome may be included if their total bilirubin is ≤ 3.0

Total serum bilirubin ≤ 2.0 mg/dL

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent

I have no health issues that prevent me from undergoing standard transplant procedures.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

HSCT Conditioning and Transplantation

Patients receive HSCT conditioning regimen followed by alloHSCT per standard of care

4-7 weeks

Multiple visits for conditioning and transplantation

CAR T Cell Infusion

Patients receive allo CMV-specific CD19-CAR T cells intravenously

1 day

1 visit (in-person)

Vaccine Administration

Patients receive CMV-MVA triplex vaccine intramuscularly on day 28 and possibly on day 56

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Monthly for the first year, then at 18, 24, 30, and 36 months, followed by yearly visits

What Are the Treatments Tested in This Trial?

Interventions

• Anti-CD19-CAR CMV-specific T-lymphocytes
• Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Trial Overview The trial tests the safety and effectiveness of CMV-specific CD19-CAR T cells combined with a CMV-MVA vaccine in treating leukemia post-stem cell transplant. It involves modifying immune cells to target cancer, followed by vaccination to enhance the immune response.

How Is the Trial Designed?

Group I: Part 2 (allo CMV-specific CD19-CAR T cells, CMV-MVA vaccine) Experimental Treatment 15 Interventions

Patients receive HSCT conditioning regimen followed by alloHSCT per standard of care. Starting 28-49 days after alloHSCT, patients receive allo CMV-specific CD19-CAR T cells IV over 10-15 minutes on day 0. Patients receive CMV-MVA triplex vaccine IM on day 28 in the absence of DLTs and may receive an additional CMV-MVA triplex vaccine IM on day 56 in the absence of DLTs during the second evaluation period. Patients undergo ECHO or MUGA, blood and optional CSF sample collection and bone marrow biopsy and aspiration throughout the study. Patient may also undergo chest x-ray and lumbar puncture as needed per PI discretion and PET/CT or CT as clinically indicated throughout the study. Additionally, patients with neurological abnormalities at baseline may undergo MRI of brain throughout the study.

Group II: Part 1 (allo CMV-specific CD19-CAR T cells Experimental Treatment 14 Interventions

Patients receive HSCT conditioning regimen followed by alloHSCT per standard of care. Starting 28-49 days after alloHSCT, patients receive allo CMV-specific CD19-CAR T cells IV over 10-15 minutes on day 0. Patients undergo ECHO or MUGA, blood and optional CSF sample collection and bone marrow biopsy and aspiration throughout the study. Patient may also undergo chest x-ray and lumbar puncture as needed per PI discretion and PET/CT or CT as clinically indicated throughout the study. Additionally, patients with neurological abnormalities at baseline may undergo MRI of brain throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+