CAR T Cell Therapy for Acute Lymphoblastic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: CNS pathology, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 4

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAR T-cell therapy for individuals with acute lymphoblastic leukemia (ALL) that has returned or not responded to previous treatments. The goal is to determine the safety and effectiveness of this treatment. It involves modifying a person's immune cells in a lab to enhance their ability to attack cancer cells. Individuals diagnosed with relapsed or treatment-resistant CD19 positive ALL might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that certain medications be stopped before participation. For example, systemic chemotherapy must be stopped at least 2 weeks before a key procedure, and there are specific timeframes for stopping steroids, vincristine, and other drugs. It's best to discuss your current medications with the study team to understand any necessary changes.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

In a previous study, researchers examined the safety of a special type of immune cell therapy in patients. These immune cells were modified in a lab to specifically target cancer cells. The study found that most patients tolerated this CAR T-cell therapy well. Common side effects included fever and low blood counts, which can usually be managed with medical care. As this is a Phase 1 trial, the main goal is to assess the treatment's safety, so researchers continue to learn about possible side effects. However, early results suggest that the treatment could be safe for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

CAR T Cell Therapy is unique because it uses genetically engineered T-lymphocytes to specifically target and destroy cancer cells expressing the CD19 protein, which is common in acute lymphoblastic leukemia (ALL). Unlike traditional chemotherapy, which broadly attacks rapidly dividing cells and can cause significant side effects, this treatment harnesses the patient's own immune system to fight the cancer more precisely. Researchers are excited about this approach because it offers a personalized treatment option with the potential for long-lasting remission, even in patients who have not responded well to existing therapies.

What evidence suggests that CAR T cell therapy might be an effective treatment for acute lymphoblastic leukemia?

Research has shown that CAR T-cell therapy can be effective for patients with acute lymphoblastic leukemia (ALL). In this trial, participants will receive huCD19-CAR T cells, specially modified T cells designed to find and destroy cancer cells by targeting a protein called CD19 on their surface. Initial findings suggest that this treatment can help patients whose leukemia has returned or not responded to other treatments. Specifically, studies have demonstrated that many patients experience a significant reduction in cancer cells after receiving this therapy. While more research is needed, early results are promising for those with this challenging condition. ^{1 2 3 4 5}

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 patients with CD19 positive B-cell acute lymphoblastic leukemia that has relapsed or is refractory. Participants must have adequate organ function and no active infections. They cannot join if they've had certain recent treatments, other cancers, central nervous system involvement by leukemia, or are pregnant.

Inclusion Criteria

Left ventricular ejection fraction (LVEF) ≥ 45%

Prohibited medications have not been administered

I don't have a fever above 38.5°C and no recent infections.

Exclusion Criteria

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

I received CAR T therapy less than 3 months ago.

I have severe heart condition limitations.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Lymphodepletion Chemotherapy

Patients undergo leukapheresis and receive lymphodepletion chemotherapy with fludarabine and cyclophosphamide

1 week

3 visits (in-person)

CAR T Cell Infusion

Patients receive huCD19-CAR T cells infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year monthly, then yearly up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The trial tests huCD19-CAR T cell therapy where a patient's immune cells are modified to attack cancer cells, combined with chemotherapy drugs fludarabine and cyclophosphamide. It aims to see if this approach is safe and effective against relapsed/refractory ALL.

How Is the Trial Designed?

Group I: Treatment (huCD19-CAR T) Experimental Treatment 14 Interventions

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.

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+

Published Research Related to This Trial

CAR-T cell therapy targeting CD19 has been FDA-approved for treating relapsed and refractory acute lymphoblastic leukemia (ALL) in children and young adults, showing promising efficacy.

Recent trials with CD22-directed CAR-T cells indicate they can also effectively target leukemia, providing a potential alternative to CD19 therapy, although challenges like toxicity management and relapse rates remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment of Relapsed and Refractory Disease. Pehlivan, KC., Duncan, BB., Lee, DW.[2019]

In a phase I/II trial involving 13 patients with B cell acute lymphoblastic leukemia (B-ALL) who relapsed after stem cell transplantation, donor-derived CD19 CAR T cells showed promising results, with 6 out of 7 patients receiving the highest doses achieving complete remission (CR) or CR with incomplete blood count recovery (CRi) by day 28.

The CAR T cell therapy demonstrated a favorable safety profile, with only mild cytokine-release syndrome reported and no severe toxicities such as graft-versus-host disease or neurotoxicity, indicating that this approach could be a viable treatment option for relapsed B-ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping Beauty-engineered CAR T cells achieve antileukemic activity without severe toxicities. Magnani, CF., Gaipa, G., Lussana, F., et al.[2021]

In a study of 15 patients with B cell acute lymphoblastic leukemia (B-ALL) who experienced extramedullary relapse, CD19 CAR-T cell therapy resulted in a high overall response rate of 93.3%, with 73.3% achieving complete response and a median duration of response of 6 months.

The therapy was associated with manageable adverse effects, including cytokine release syndrome in 86.7% of patients, but these were well controlled, indicating that CD19 CAR-T cell therapy is both effective and relatively safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CD19 CAR-T cell therapy for patients with B cell acute lymphoblastic leukemia involving extramedullary relapse. Huang, L., Zhang, M., Wei, G., et al.[2022]

Adoptive cellular therapy using CD19 CAR T cells has shown remarkable efficacy in achieving remission in 67-90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), indicating a promising treatment option for this high-risk group.

While CD19 CAR T-cell therapy can lead to significant toxicities such as cytokine release syndrome and neurologic dysfunction, these effects are generally manageable with supportive care, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Tasian, SK., Gardner, RA.[2020]

CAR T-cell therapy has significantly improved treatment options for acute lymphoblastic leukemia (ALL), achieving over 70% complete remission rates in clinical trials, and has been FDA approved for use in relapsed/refractory cases.

Despite its effectiveness, challenges such as relapse, resistance, and loss of CAR T-cell persistence pose barriers to long-term remission, highlighting the need for advancements in CAR T-cell engineering to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving CAR T-cells: The next generation. Marple, AH., Bonifant, CL., Shah, NN.[2021]

CD19/20/22 CAR T-cells have been developed to effectively target B-lineage acute lymphoblastic leukemia (BL-ALL) that has relapsed with CD19(-) disease, showing efficacy in both laboratory and animal models.

These CAR T-cells maintain their effectiveness against CD19(+) disease while also being able to kill CD19(-) blasts, suggesting they could serve as a new treatment option for patients who do not respond to traditional CD19-targeting therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression. Fousek, K., Watanabe, J., Joseph, SK., et al.[2022]

In a phase 1 trial of 53 adults with relapsed B-cell acute lymphoblastic leukemia, 83% achieved complete remission after receiving CD19-specific CAR T cells, indicating high initial efficacy.

Patients with a low disease burden before treatment experienced significantly longer overall survival (20.1 months) and fewer severe side effects, such as cytokine release syndrome, compared to those with a higher disease burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. Park, JH., Rivière, I., Gonen, M., et al.[2023]

CAR T cell therapy, specifically targeting the CD19 antigen, has shown high response rates in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), indicating its potential as a new treatment option.

Despite its effectiveness, CAR T cell therapy is associated with severe toxicities like cytokine release syndrome and neurotoxicity, which pose challenges for its widespread use and highlight the need for ongoing improvements in the technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice. Luskin, MR., DeAngelo, DJ.[2018]

In a study of 168 patients with refractory/relapsed B-cell acute lymphoblastic leukemia, those who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) after CAR-T therapy had similar long-term survival rates compared to those who underwent haplo-HSCT after achieving minimal residual disease-negative complete remission from chemotherapy.

Patients who achieved a first complete remission (CR1) after chemotherapy had better overall survival and leukemia-free survival rates than those who had a second or more complete remission (≥CR2), highlighting the importance of achieving an earlier remission for better transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparable outcomes in patients with B-cell acute lymphoblastic leukemia receiving haploidentical hematopoietic stem cell transplantation: Pretransplant minimal residual disease-negative complete remission following chimeric antigen receptor T-cell therapy versus chemotherapy. Yang, TT., Meng, Y., Kong, DL., et al.[2022]

An 11-year-old girl with relapsed acute B lymphoblastic leukemia (B-ALL) was treated with fourth generation CD19 CAR-T therapy, which was found to be effective and safe, resulting in a negative minimal residual disease after treatment.

Despite initial success and 10 months of disease-free survival, the patient ultimately relapsed due to increasing TEL-AML1 gene copies, highlighting the need for ongoing monitoring and potential further interventions in CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chimeric antigen receptors T cells in treatment of a relapsed pediatric acute lymphoblastic leukemia, relapse after allogenetic hematopoietic stem cell transplantation: case report and review of literature review]. Zuo, Y., Wang, J., Lu, A., et al.[2020]

The study found that Tn/mem-derived CD19-CAR T cells were safe and effective in treating adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL), with 87% of participants achieving complete remission or partial remission.

Among the 46 participants treated, those with Philadelphia-like ALL and extramedullary disease showed high response rates, and undergoing allogeneic hematopoietic cell transplantation after treatment significantly improved relapse-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Favorable Activity and Safety Profile of Memory-Enriched CD19-Targeted Chimeric Antigen Receptor T-Cell Therapy in Adults with High-Risk Relapsed/Refractory ALL. Aldoss, I., Khaled, SK., Wang, X., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02146924

Study Details | NCT02146924 | Cellular Immunotherapy in ... Patients receive CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/nem-enriched T cells IV over 15 minutes on day 0. Patients who have evidence of disease, whose tumor(s) ...

2. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/cd19car-cd28-cd3zeta-egfrt-expressing-tn-mem-enriched-t-lymphocytes

Clinical Trials Using CD19CAR-CD28-CD3zeta-EGFRt- ... Review the clinical trials studying cd19car-cd28-cd3zeta-egfrt-expressing tn/mem-enriched t-lymphocytes on this list and use the filters to refine the ...

3. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/cd19car-cd28-cd3zeta-egfrt-expressing-tn-mem-enriched-t-lymphocytes

CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem- ... ... CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T lymphocytes. A preparation of genetically modified lymphocytes comprised of CD62L-positive naïve and memory T ...

4. withpower.com withpower.com/trial/phase-1-leukemia-7-2024-b6be3

CAR T Cell Therapy for Acute Lymphoblastic Leukemia This Phase 1 medical study run by City of Hope Medical Center is evaluating whether CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes will ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11539471/

Advances in CAR-T therapy for central nervous system tumors This review examined the research progress of chimeric antigen receptor T-cell therapy in gliomas, medulloblastomas, and lymphohematopoietic tumors of the ...