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 trial tests a new treatment for individuals with high-risk acute lymphoblastic leukemia, a type of blood cancer. The therapy involves engineering T cells (immune cells) to target and destroy cancer cells, known as Anti-CD19-CAR CMV-specific T-lymphocytes, and includes a vaccine to boost the immune response. The trial aims to determine if this combination is safe and effective after a stem cell transplant. Individuals with acute lymphoblastic leukemia that is difficult to treat or has recurred after treatment might be suitable candidates. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use systemic steroids, and if you have an active autoimmune disease requiring immune suppressive therapy, you may not be eligible.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that CD19-targeted CAR T-cell therapy is generally well-tolerated. Studies have found that this treatment can lead to complete remission in 70%–90% of patients with recurring blood cancers like acute lymphoblastic leukemia. While side effects can occur, the overall safety is promising, with many patients experiencing manageable symptoms.

Previous studies suggest that the CMV-MVA vaccine is safe and helps strengthen the immune system. Participants in trials have tolerated the vaccine well, with few serious side effects reported. It has effectively boosted the body's defense against cytomegalovirus, a common virus that can cause problems in people with weakened immune systems.

Both treatments have shown encouraging safety results. However, this trial is in an early phase, so the complete safety picture is still being studied. Researchers will closely monitor participants for any adverse events as they continue to evaluate these therapies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for acute lymphoblastic leukemia because they use a novel approach known as CAR T-cell therapy. Unlike traditional treatments like chemotherapy and radiation, which broadly target cancer cells, CAR T-cells are engineered to specifically recognize and attack leukemia cells by targeting a protein called CD19 on their surface. Additionally, one of the treatment arms includes a CMV-MVA vaccine, which is given to further stimulate the immune system's response, potentially enhancing the effectiveness of the CAR T-cells. This combination could offer a more precise and powerful approach to eliminating cancer cells while minimizing damage to healthy cells.

What evidence suggests that this trial's treatments could be effective for acute lymphoblastic leukemia?

Studies have shown that CD19 CAR-T cell therapy can effectively treat B-cell acute lymphoblastic leukemia. It eliminates residual cancer cells and improves long-term survival. Research indicates that this treatment is generally safe, with manageable side effects. In this trial, some participants will receive CD19 CAR-T cell therapy alone, while others will receive both CD19 CAR-T cell therapy and the CMV-MVA vaccine. The CMV-MVA vaccine aims to strengthen the immune system against cancer cells in patients who have undergone a stem cell transplant. Although still under study, early data suggest it boosts immunity and helps prevent cytomegalovirus reactivation, which is crucial for patient safety post-transplant. Both the CAR-T therapy and the vaccine offer promising ways to combat high-risk leukemia, especially when combined. ^{2 4 6 7 8}

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10776428/

Donor-derived Anti-CD19 CAR T cells GC007g for relapsed or ... Although chimeric antigen receptor-modified T cells (CAR T) cell therapy has been widely reported in improving the outcomes of B-cell acute lymphoblastic ...

2. nature.com nature.com/articles/s41409-025-02691-2

Safety and efficacy of autologous humanized CD19 CAR-T ... Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).

3. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1672509/full

Effective MRD clearance and long-term survival with CD19 ... Conclusion: CD19 CAR-T therapy demonstrates highly effective MRD clearance and provides long-term survival benefits with a manageable safety ...

4. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-cd19-car-cmv-specific-t-lymphocytes

Clinical Trials Using Anti-CD19-CAR CMV-specific T- ... Review the clinical trials studying anti-cd19-car cmv-specific t-lymphocytes on this list and use the filters to refine the results by age and location.

5. ehoonline.biomedcentral.com ehoonline.biomedcentral.com/articles/10.1186/s40164-024-00593-5

Prominent efficacy and good safety of sequential CD19 ... Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10604728/

CAR T-Cells in Acute Lymphoblastic Leukemia: Current Status ... Considering that only anti-CD19 CAR T-cells are the currently FDA-approved CAR T-cell therapy for B-ALL, we can classify relapse to either CD19- ...

7. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00554-0/fulltext

Donor-derived Anti-CD19 CAR T cells GC007g for ... CD19-targeted CAR T cell therapy has shown promising results in which the complete remission (CR) rates as high as 70%–90% in treating relapsed ...

8. ashpublications.org ashpublications.org/blood/article/127/26/3312/35352/CD19-targeted-CAR-T-cell-therapeutics-for

CD19-targeted CAR T-cell therapeutics for hematologic ... We review clinical results reflecting the investigational use of CD19-targeted CAR T-cell therapeutics in patients with B-cell hematologic malignancies.