CAR T-Cell Therapy for Leukemia

Recruiting at 1 trial location

Overseen By Melissa S Varghese, M.S.

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Stephan Grupp MD PhD

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Hepatitis B, Hepatitis C, HIV, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

89 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for producing a cancer treatment called huCART19 (Autologous Humanized CD19-Directed Chimeric Antigen Receptor T-Cells) for individuals with B cell Acute Lymphoblastic Leukemia (B-ALL). Researchers aim to determine the safety and effectiveness of this new manufacturing process. The trial will explore different doses to identify the optimal one, particularly for those whose previous treatments were unsuccessful. Individuals with B-ALL and a history of treatment resistance might be suitable candidates. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in participants and measure its effectiveness in an initial group, offering a chance to be among the first to benefit from this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use systemic steroids or immunosuppressants at the time of cell infusion or collection. Some steroids are allowed at other times, and inhaled steroids or physiologic replacement hydrocortisone are permitted.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that huCART19, a treatment using a patient's own modified immune cells, has been studied in people with various blood cancers. One study with 58 patients who had B-cell Acute Lymphoblastic Leukemia (B-ALL) found the treatment generally well-tolerated. However, some patients experienced side effects like cytokine release syndrome (CRS), a strong reaction to the treatment, and neurological issues.

Another study with a similar group of patients found that while the treatment was safe, the benefits, such as cancer remission, did not last long for everyone. Despite the side effects, the treatment has shown promise for some patients with limited other options.

The current trial is in its early stages, focusing on finding the best dose to reduce side effects and increase benefits. This phase usually involves fewer patients and is closely monitored to ensure safety.

Patients considering joining a trial like this should discuss the potential risks and benefits with their healthcare provider to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for leukemia?

Researchers are excited about huCART19 because it offers a novel approach to treating leukemia with a focus on precision and adaptability. Unlike traditional chemotherapy or radiation that broadly target cancer cells, huCART19 employs a chimeric antigen receptor (CAR) T-cell technique, specifically engineered to recognize and attack CD19 proteins found on leukemia cells. This personalized therapy has the potential to be more effective and less harmful to healthy cells, making it a promising option for patients who have relapsed or are resistant to existing CAR T-cell therapies.

What evidence suggests that huCART19 could be an effective treatment for leukemia?

Research has shown that a new treatment called humanized CAR T cells, specifically huCART19, may help treat B-cell Acute Lymphoblastic Leukemia (B-ALL) that has returned or is unresponsive to other treatments. In studies with 58 patients with this leukemia, these CAR T cells proved effective. Patients experienced a decrease in leukemia cells, indicating that the treatment can locate and destroy cancer cells. In this trial, participants will join either the Dose Escalation Arm or the Dose Expansion Arms to evaluate the safety and effectiveness of huCART19. However, it remains too early to determine if these humanized CAR T cells outperform older versions. Overall, the early results are promising for those seeking new treatment options for B-ALL. ^{1 2 4 6 7}

Who Is on the Research Team?

Allison Barz Leahy, MD

Principal Investigator

Children's Hospital of Philadelphia

Stephan Grupp, MD,PhD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 0-29 with B-cell Acute Lymphoblastic Leukemia (B-ALL) who have either relapsed or didn't respond well to previous treatments. Participants must have CD19+ ALL, adequate organ function, and a performance score of at least 50. They should not be pregnant, nursing, or have active infections like hepatitis B/C or HIV.

Inclusion Criteria

My brain-related disease is responding to treatment.

I had a poor response to previous B cell therapy.

Signed Informed Consent

Exclusion Criteria

I currently have an infection that is not under control.

My brain condition is getting worse despite treatment, or I have brain lesions that could make treatment risky.

I am HIV positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1 dose escalation using a '3+3' design to establish the recommended phase 2 dose of huCART19 cells

Varies

Dose Expansion

Phase 2b dose expansion where subjects receive the highest safe dose of huCART19 cells

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Humanized CD19-Directed Chimeric Antigen Receptor T-Cells (huCART19)

Trial Overview The study tests the safety and effectiveness of huCART19 T cells made using a new method called CliniMACS Prodigy platform in patients with B-ALL. It aims to see if this second-generation process can improve treatment outcomes for these patients.

How Is the Trial Designed?

Group I: Dose Expansion Arms Experimental Treatment 1 Intervention

If at least one dose level of the dose escalation phase is determined to be safe, the phase 2b dose expansion phase of the trial will be opened to enrollment. Subjects will receive the highest dose of huCART19 cells that were determined to be safe in the dose escalation part of the trial. 2 cohorts are planned: * Cohort A (relapsed/refractory, CAR T cell naïve) * Cohort B (prior treatment with CD19-directed CAR T cells)

Group II: Dose Escalation Arm Experimental Treatment 1 Intervention

The phase 1 dose escalation portion of the trial will use a standard "3+3" design to establish the recommended phase 2 dose of huCART19 cells in patients with subjects with prior treatment with CD19-directed CAR T cells. Two dose escalations of huCART19 are planned for the dose escalation phase.

Autologous Humanized CD19-Directed Chimeric Antigen Receptor T-Cells (huCART19) is already approved in United States for the following indications:

Approved in United States as huCART19 for:

• B-cell Acute Lymphoblastic Leukemia (B-ALL)

Who Is Running the Clinical Trial?

Stephan Grupp MD PhD

Lead Sponsor

Trials

5

Recruited

370+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Published Research Related to This Trial

Chimeric antigen receptor (CAR) therapy, particularly targeting CD19, has shown significant efficacy in treating patients with chemorefractory B cell malignancies, leading to its potential regulatory approval as a cell-based immunotherapy.

While CAR therapy is effective, it is associated with toxicities such as cytokine release syndrome, neurotoxicity, and B cell aplasia, which require careful management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology and clinical application of CAR T cells for B cell malignancies. Davila, ML., Sadelain, M.[2023]

Chimeric antigen receptor-modified T cells targeting CD19 showed significant clinical activity in two children with relapsed acute lymphoblastic leukemia (ALL), leading to complete remission in one patient for 11 months after treatment.

While the treatment was effective, both patients experienced severe adverse events, including cytokine-release syndrome and B-cell aplasia, highlighting the need for careful monitoring and potential additional targeting strategies due to the emergence of CD19-negative tumor cells in one patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. Grupp, SA., Kalos, M., Barrett, D., et al.[2023]

In a pilot clinical trial involving 9 patients with relapsed or chemotherapy-refractory B-cell acute lymphocytic leukemia (B-ALL), genetically modified T cells targeting the CD19 antigen showed a 56% overall survival rate at 18 weeks.

The study demonstrated that donor-derived anti-CD19 CAR T cells can lead to significant regression of both hematopoietic and extramedullary B-ALL, although some patients experienced grade 2-3 graft-versus-host disease (GVHD) after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia. Dai, H., Zhang, W., Li, X., et al.[2021]

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), compared to a 30% response rate with traditional chemotherapy.

The therapy involves genetically modifying T cells to express a chimeric antigen receptor, allowing them to effectively target and eliminate cancer cells, although it is important to note that there are unique toxicities associated with this treatment that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Davila, ML., Brentjens, RJ.[2023]

CAR T cell therapy has shown effectiveness in treating various hematological malignancies, including B lymphoblastic leukemia and lymphoma, with advancements in CD19, BCMA, and CD7 CAR-T cells.

Research is ongoing to improve CAR T cell therapies by developing multi-target and universal CAR-T cells, as well as iPSC-derived CAR cells, aiming for enhanced efficacy and reduced side effects in treating myeloid malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress on CAR-T cell therapy for hematological malignancies. Hu, K., Huang, Y., Hu, Y., et al.[2022]

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]

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 and CD20 has shown a promising overall response rate of 61% in treating B-cell hematologic malignancies, with a complete response rate of 42% and partial response rate of 19% across 16 studies involving 195 patients.

However, the therapy is associated with significant adverse events, including cytokine release syndrome and neurotoxicity (both at 33%), and B-cell aplasia in 54% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. Riaz, IB., Zahid, U., Kamal, MU., et al.[2023]

Chimeric-antigen-receptor T cells (CAR-T) targeting CD19 are associated with several adverse drug reactions (ADRs), with the most common being cytokine release syndrome (CRS), neurological disorders, and hematological disorders, as identified in a study analyzing 1783 safety reports.

While CAR-T therapy can lead to severe ADRs, particularly in the week following administration, the overall fatality rate from these reactions is relatively low at 5.5%, though serious conditions like hemophagocytic-lymphohistiocytosis and infections require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study. Dolladille, C., Ederhy, S., Ezine, E., et al.[2021]

In a phase I clinical trial involving 20 patients with B-cell lymphoma, 55% achieved complete remission using the new anti-CD19 CAR T-cell therapy Hu19-CD828Z, demonstrating its effectiveness against lymphoma.

Hu19-CD828Z therapy resulted in significantly lower rates of severe neurologic toxicity (5%) compared to the previously tested FMC63-28Z therapy (50%), likely due to reduced cytokine release associated with the Hu19-CD828Z CAR design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Brudno, JN., Lam, N., Vanasse, D., et al.[2021]

In a phase I trial involving 12 younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia, the use of chimeric antigen receptor T cells targeting CD19 and CD22 showed manageable toxicity levels.

Out of the 12 patients, 5 achieved complete responses, indicating promising efficacy of this treatment approach in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD19-CD22 Aids Younger Patients with ALL. [2021]

CD4 is identified as a promising target for CAR-T cell therapy in treating acute myeloid leukemia (AML), as it is expressed in certain AML subtypes but not on normal hematopoietic stem cells, allowing for targeted treatment.

CD4 redirected CAR-T cells effectively eliminated CD4-expressing AML cells in laboratory settings and demonstrated strong anti-leukemic effects in a mouse model, suggesting potential for clinical application in refractory AML cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Targeting of Human Acute Myeloid Leukemia Using CD4-specific Chimeric Antigen Receptor (CAR) T Cells and NK Cells. Salman, H., Pinz, KG., Wada, M., 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]

Chimeric antigen receptor (CAR) T cells targeting both CD123 and CD33, in addition to CLL-1, showed improved anti-tumor activity against acute myeloid leukemia (AML) cells, especially when the target cells expressed low levels of these antigens.

The study demonstrated that dual targeting led to enhanced T cell activation and better tumor control in vivo, resulting in improved survival rates in animal models without any antigen escape in residual tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combinatorial antigen targeting strategies for acute leukemia: application in myeloid malignancy. Atilla, PA., McKenna, MK., Watanabe, N., et al.[2023]

Citations

1. 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).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9944646/

Safety and efficacy of autologous and allogeneic humanized ... Here, we report the results of 58 patients with R/R B-ALL with a median follow-up of 1.1 years who received humanized CD19-targeted CAR-T cells ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05480449

Study Details | NCT05480449 | Autologous HuCART19 T ... This study will determine the safety and efficacy of moving to a second-generation manufacturing process using the CliniMACS Prodigy platform to manufacture ...

4. ashpublications.org ashpublications.org/bloodadvances/article/9/8/1916/536668/Humanizing-CAR-T-cell-therapy-in-B-ALL

Humanizing CAR T-cell therapy in B-ALL | Blood Advances The collective data suggest that it is too early to know whether humanized CAR T cells offer benefits over murine constructs in B-ALL. To ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.3007

Efficacy of humanized CD19-targeted chimeric antigen ... We now report on retreatment with murine (CTL019) or humanized (CTL119) CD19-directed CAR T cells. Methods: Patient-derived T cells were ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03792633

NCT03792633 | Study of huCART19 for Very High-Risk ... This is a phase 2 study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) with CD19 expressing relapsed and refractory B-cell ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6511615/

Survival outcomes and efficacy of autologous CD19 ... 9 Zhou et al reported the safety and efficacy of CD20 and CD19 CAR-T cells in 185 patients.10 Anwer et al included allogeneic T cells, though most CAR-T cell ...