CART19 for Acute Lymphoblastic Leukemia

Overseen By Melissa S Varghese, M.S.

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Stephan Grupp MD PhD

Must not be taking: Systemic steroids

Disqualifiers: Hepatitis B, Hepatitis C, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

133 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Murine CART19, a type of CAR T-cell therapy, for various types of acute lymphoblastic leukemia (ALL) in children and young adults. Researchers aim to determine the treatment's effectiveness for patients with specific leukemia profiles, such as those with fewer chromosomes than usual, certain genetic changes, or a type of relapse affecting the brain. Suitable candidates include individuals diagnosed with B-ALL who meet specific genetic or relapse criteria, such as certain chromosome changes or a central nervous system relapse without prior radiation or bone marrow transplant. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in leukemia therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use systemic steroids at the time of cell infusion or collection. Other medications might be allowed, so it's best to discuss your specific situation with the trial team.

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

Research has shown that treatments like murine CART19, such as tisagenlecleucel (Kymriah®), have been studied for safety. These treatments are generally well-tolerated, but risks exist. Common side effects include cytokine release syndrome (CRS), where the immune system overreacts, and immune effector cell-associated neurotoxicity syndrome (ICANS), which can affect the brain.

Despite these risks, the treatments have shown positive results. In some studies, about 8 out of 10 patients experienced remission, meaning they had a period without disease symptoms after treatment. Real-world data also supports the safety of these treatments, showing that side effects can often be managed with medical care.

This trial is in an early phase, so the treatment's safety is still under close study. Knowing these potential risks and benefits can help anyone considering joining the trial make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute lymphoblastic leukemia?

Researchers are excited about Murine CART19 for treating Acute Lymphoblastic Leukemia (ALL) because it offers a novel approach using engineered T-cells. Unlike traditional treatments like chemotherapy and radiation, which can harm healthy cells, CART19 specifically targets cancer cells by recognizing a protein called CD19 on their surface. This precision potentially leads to fewer side effects and more effective elimination of leukemia cells. Additionally, CART19’s ability to be tailored for specific genetic profiles of leukemia, like hypodiploid B-ALL and t(17;19) B-ALL, makes it a promising personalized therapy, offering hope for patients with high-risk forms of leukemia.

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

Research has shown that Murine CART19, similar to Kymriah® (tisagenlecleucel), offers promising results for treating certain types of B-cell acute lymphoblastic leukemia (B-ALL). In earlier studies, about 80% of patients who received a similar treatment went into remission, with no cancer cells found three months after treatment. This trial will evaluate Murine CART19 in various patient groups, including those with hypodiploid B-ALL, t(17;19) B-ALL, very high-risk KMT2A B-ALL in infants, and those with central nervous system (CNS) relapse. This therapy uses specially modified immune cells to locate and destroy leukemia cells and has proven effective in children and young adults with B-ALL that has returned or is difficult to treat. Real-world evidence also supports its success, showing high remission rates and improved outcomes for patients. This treatment harnesses the body's immune system to attack and kill cancer cells, offering hope for those with challenging cases of leukemia. ^{1 2 5 6 7}

Who Is on the Research Team?

Stephan Grupp, MD, PhD

Principal Investigator

Children's Hospital of Philadelphia

Amanda DiNofia, MD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for pediatric and young adult patients (0-29 years) with specific types of B-cell Acute Lymphoblastic Leukemia (B-ALL), including those with hypodiploid karyotype, t(17;19) translocation, high-risk KMT2A rearrangement, or CNS relapse without prior cranial radiation or bone marrow transplant. Participants must have CD19+ expression on leukemia cells and meet organ function criteria.

Inclusion Criteria

My leukemia cells test positive for CD19.

I have B-cell Acute Lymphoblastic Leukemia that is CD19 positive.

I am between 0 and 29 years old.

Exclusion Criteria

I have not had brain radiation or bone marrow transplant for my current CNS relapse.

I am HIV positive.

I do not have any ongoing infections that aren’t responding to treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CART19 therapy targeting CD19 in pediatric and young adult patients with specific B-ALL subtypes

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including relapse-free survival and event-free survival assessments

1 year

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Murine CART19

Trial Overview The study tests the effectiveness of Murine CART19 therapy in four different patient cohorts with various high-risk conditions of B-ALL. It's an open-label phase 2 trial where all participants receive the experimental treatment to see how well it works against their leukemia.

How Is the Trial Designed?

Group I: Subjects with t(17;19) B-ALL Experimental Treatment 1 Intervention

Group II: Subjects with hypodiploid B-ALL Experimental Treatment 1 Intervention

Group III: Subjects with central nervous system (CNS) relapse Experimental Treatment 1 Intervention

who did not receive cranial radiation (XRT) or bone marrow transplantation (BMT)

Group IV: Infant subjects with very high risk KMT2A B-ALL Experimental Treatment 1 Intervention

Murine CART19 is already approved in European Union, United States for the following indications:

Approved in European Union as tisagenlecleucel for:

• B-cell acute lymphoblastic leukemia (ALL)
• Diffuse large B-cell lymphoma (DLBCL)

Approved in United States as tisagenlecleucel for:

• B-cell precursor acute lymphoblastic leukemia (ALL)
• Diffuse large B-cell lymphoma (DLBCL)

Who Is Running the Clinical Trial?

Stephan Grupp MD PhD

Lead Sponsor

Trials

5

Recruited

370+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

In a global study involving 75 pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), the CAR T-cell therapy tisagenlecleucel achieved an impressive overall remission rate of 81% within 3 months, with all responders showing no minimal residual disease.

While 73% of patients experienced serious adverse events, including cytokine release syndrome in 77% and neurologic events in 40%, these effects were mostly manageable and reversible, indicating that tisagenlecleucel can provide durable remission despite the risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. Maude, SL., Laetsch, TW., Buechner, J., et al.[2022]

Tisagenlecleucel, a CAR-T cell therapy, shows high overall remission rates of 69% to 93% in patients with relapsed/refractory B-cell acute lymphoblastic leukemia, with durable 12-month relapse-free survival rates of 55% to 59%.

However, the treatment is associated with significant risks, including potentially life-threatening cytokine release syndrome in 77% to 100% of patients and neurotoxicity in 31% to 45%, highlighting the need for careful patient selection and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in Acute Lymphoblastic Leukemia: A Review of the Literature and Practical Considerations. Halford, Z., Anderson, MK., Bennett, LL., et al.[2021]

Tisagenlecleucel, a CAR T cell therapy for relapsed/refractory B cell acute lymphoblastic leukemia, showed a high incidence of grade 3/4 adverse events (77% of patients), including cytokine-release syndrome (79%) and prolonged cytopenias (40%).

Despite the significant adverse events, the therapy led to complete remission in patients, with effective management of complications such as CRS using tocilizumab and corticosteroids, and a low incidence of severe infections after one year due to immunoglobulin replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia. Levine, JE., Grupp, SA., Pulsipher, MA., et al.[2022]

Tisagenlecleucel (Kymriah) is an effective treatment for B-cell precursor acute lymphoblastic leukemia (ALL) in patients up to 25 years old, achieving a complete remission rate of 63% in a study of 63 participants, with all remissions showing minimal residual disease (MRD) below 0.01%.

While the treatment shows promise, it is associated with serious side effects, including cytokine release syndrome (79%) and neurologic events (65%), but the overall benefit-risk profile is considered acceptable for patients with resistant forms of ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Tisagenlecleucel for Treatment of Patients with Relapsed or Refractory B-cell Precursor Acute Lymphoblastic Leukemia. O'Leary, MC., Lu, X., Huang, Y., et al.[2020]

In a study of 79 pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia, those who responded to the CAR T-cell therapy tisagenlecleucel showed approximately double the expansion of the therapy in their blood compared to nonresponders, indicating a strong correlation between cellular expansion and treatment efficacy.

The therapy demonstrated persistence in responders for over two years, and its expansion continued even after treatment with tocilizumab, which is used to manage cytokine release syndrome, suggesting that tisagenlecleucel can remain effective despite potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacology of Tisagenlecleucel in B-cell Acute Lymphoblastic Leukemia. Mueller, KT., Waldron, E., Grupp, SA., et al.[2020]

Tisagenlecleucel is the first FDA-approved CD19-targeted CAR T cell therapy specifically for pediatric patients with pre-B-cell acute lymphoblastic leukemia (B-ALL), showing excellent responses in a multicenter phase II trial for those with highly refractory disease.

While CAR T cell therapy can lead to durable remissions in many patients, close monitoring for unique toxicities such as cytokine release syndrome and neurotoxicity is essential after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 CAR T Cells for the Treatment of Pediatric Pre-B Cell Acute Lymphoblastic Leukemia. Pacenta, HL., Laetsch, TW., John, S.[2020]

In a study of 14 infants with B-cell acute lymphoblastic leukemia (B-ALL) treated with tisagenlecleucel, 64% achieved minimal residual disease-negative remission, indicating significant efficacy of this CAR T-cell therapy in a population previously excluded from clinical trials.

The therapy was generally well-tolerated, with only 3 patients experiencing severe cytokine release syndrome and no reports of neurotoxicity, suggesting that tisagenlecleucel is a safe treatment option for infants with this aggressive form of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world use of tisagenlecleucel in infant acute lymphoblastic leukemia. Moskop, A., Pommert, L., Baggott, C., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10294746/

Kymriah® (tisagenlecleucel) – An overview of the clinical ... This article presents a high-level overview of the clinical development journey of tisagenlecleucel, including its efficacy outcomes and safety considerations.

2. kymriah-hcp.com kymriah-hcp.com/acute-lymphoblastic-leukemia-children/efficacy

KYMRIAH® (tisagenlecleucel) Efficacy Data & Clinical Trials About 8/10 patients achieved minimal residual disease negative (MRD-negative) remission at 3 months after treatment with KYMRIAH (tisagenlecleucel).

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07039383

NCT07039383 | A Real-world Study of the Effectiveness ... This was a retrospective, cross-sectional, center-based chart review study that collected real-world data for relapsed/refractory (R/R) ...

4. ashpublications.org ashpublications.org/bloodadvances/article/9/20/5249/537901/Real-world-data-for-tisagenlecleucel-in-patients

Real-world data for tisagenlecleucel in patients with R/R B-ALL This represents the largest data set for any chimeric antigen receptor T-cell therapy in pediatric and young adult patients with B-ALL. Outcomes in the ...

5. astctjournal.org astctjournal.org/article/S2666-6367(25)00363-X/fulltext

Kymriah Real-World Effectiveness and Functional ... 65% of pts who went on to alloSCT (22/34) were in B-cell recovery at time of transplant; 71% of pts (24/34) were relapse-free prior to alloSCT. Safety and ...

6. astctjournal.org astctjournal.org/article/S2666-6367(25)00362-8/fulltext

Excellent Outcomes in Patients Receiving ... Safety outcomes included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and other severe complications.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11095278/

Comprehensive analysis of the efficacy and safety of CAR ... CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events.