What is the mechanism of action of this treatment?

The most common treatments for Acute Lymphoblastic Leukemia (ALL) include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy uses drugs to kill rapidly dividing cancer cells, while targeted therapy involves drugs that specifically target genetic mutations or proteins that contribute to cancer growth, such as tyrosine kinase inhibitors for Philadelphia chromosome-positive ALL. Immunotherapy, including treatments like huCART19 cells, redirects a patient's own T cells to target and destroy CD19-expressing B cells, which are often malignant in ALL. This approach is significant for ALL patients as it offers a highly specific attack on cancer cells, potentially leading to better outcomes and fewer side effects compared to traditional therapies.

What side effects are associated with this type of intervention?

Common treatments for Acute Lymphoblastic Leukemia (ALL), such as CAR-T cell therapies like huCART19, often lead to side effects including cytokine release syndrome (CRS), which can cause fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and difficulty breathing. Neurological toxicities are also common, presenting as confusion, seizures, or encephalopathy. Other side effects of ALL treatments, including chemotherapy, can include myelosuppression (leading to increased risk of infection, anemia, and bleeding), gastrointestinal symptoms (nausea, vomiting, diarrhea), and organ toxicity (liver, kidney). Long-term effects may include secondary malignancies and endocrine dysfunctions.

What prior FDA approvals exist?

The FDA has approved several CAR-T cell therapies for the treatment of Acute Lymphoblastic Leukemia (ALL), particularly for patients with relapsed or refractory disease. Notably, Tisagenlecleucel (Kymriah) was the first CAR-T cell therapy approved for pediatric and young adult patients with B-cell ALL. This therapy involves redirecting autologous T cells to target and destroy CD19-expressing B cells, similar to the huCART19 cells being studied. Another approved CAR-T therapy is Brexucabtagene autoleucel (Tecartus), which is also directed against CD19 and used in certain types of B-cell malignancies. These therapies have shown significant efficacy in inducing remissions in patients who have not responded to conventional treatments.

What other types of research exist?

Promising novel alternatives to huCART19 cells for treating Acute Lymphoblastic Leukemia (ALL) include: 1) Bispecific T-cell Engagers (BiTEs) such as blinatumomab, which redirect T cells to target CD19-expressing B cells. 2) Other CAR-T cell therapies targeting different antigens like CD22 (e.g., moxetumomab pasudotox). 3) Antibody-drug conjugates (ADCs) like inotuzumab ozogamicin, which deliver cytotoxic agents directly to cancer cells. 4) Next-generation CAR-T cells with enhanced persistence and reduced toxicity. These therapies offer alternative mechanisms of action and may provide options for patients who do not respond to or relapse after huCART19 treatment.

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CAR T-cell Therapy

huCART19 for Acute Lymphoblastic Leukemia

Phase 2

Waitlist Available

Led By Shannon Maude, MD, PhD

Research Sponsored by University of Pennsylvania

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

ii. First marrow relapse of B-ALL at < 36 months from diagnosis OR iii. 2nd or greater relapse OR

CD19+ relapse after prior cell therapy

Must not have

Active hepatitis B or active hepatitis C.

CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 28 days

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment that uses a patient's own modified immune cells to fight cancer in young patients who have not responded well to other treatments or have relapsed. This approach extends the capacity of the patient's own immune cells to detect and eliminate cancer cells.

Who is the study for?

This trial is for children and young adults aged 1-29 with high-risk B-cell acute lymphoblastic leukemia (B-ALL) that hasn't responded well to other treatments, or has come back after treatment. Participants must have CD19+ cancer cells, be in good enough health to undergo the therapy, and agree to use birth control if they can have children.

What is being tested?

The study tests huCART19, a type of immunotherapy where a patient's own T cells are modified to target CD19 on leukemia cells. It focuses on those with very poor prognosis using standard chemotherapy or who've had an inadequate response or relapse after previous cell therapies.

What are the potential side effects?

Potential side effects may include reactions related to the immune system attacking normal cells by mistake (autoimmune responses), symptoms at the infusion site, tiredness, digestive issues like nausea or diarrhea, blood-related problems such as anemia or clotting issues, and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My B-ALL has relapsed for the first time in less than 3 years or I've had multiple relapses.

Select...

My cancer returned after cell therapy and is CD19 positive.

Select...

My B-cell ALL has returned or is not responding to treatment.

Select...

I have very high-risk B-ALL or high-risk relapsed B-ALL.

Select...

I cannot have a stem cell transplant from a donor.

Select...

My previous cell therapy didn't fully work.

Select...

My cancer still shows CD19 after treatment targeting CD19.

Select...

My condition has worsened or returned at least twice after treatment.

Select...

My recent blood cancer diagnosis did not respond to initial treatment.

Select...

My kidney function, based on my age and gender, is normal.

Select...

My cancer did not respond to at least 2 initial treatments or 1 re-treatment.

Select...

My disease did not respond to at least 2 initial treatments or 1 re-treatment.

Select...

I have no health issues that prevent me from undergoing a stem cell transplant.

Select...

My cancer still shows CD19 after treatment.

Select...

My leukemia did not respond to initial treatment.

Select...

I am mostly active and can do things for myself.

Select...

I am between 3 months and 29 years old.

Select...

I have had a stem cell transplant.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have active hepatitis B or C.

Select...

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

Select...

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

Select...

I am currently receiving treatment for active graft-versus-host disease.

Select...

I am HIV positive.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 28 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~28 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 28 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Overall Remission Rate (Cohort A)

Overall Remission Rate (Cohort B)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Poor Response to Prior B Cell Directed Engineered cell therapyExperimental Treatment1 Intervention

Group II: Newly Diagnosed VHR B-ALL or High-Risk Relapse of BExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

huCART19

2019

Completed Phase 2

~190

0 / 23Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Acute Lymphoblastic Leukemia (ALL) include chemotherapy, targeted therapy, and immunotherapy. Chemotherapy uses drugs to kill rapidly dividing cancer cells, while targeted therapy involves drugs that specifically target genetic mutations or proteins that contribute to cancer growth, such as tyrosine kinase inhibitors for Philadelphia chromosome-positive ALL. Immunotherapy, including treatments like huCART19 cells, redirects a patient's own T cells to target and destroy CD19-expressing B cells, which are often malignant in ALL. This approach is significant for ALL patients as it offers a highly specific attack on cancer cells, potentially leading to better outcomes and fewer side effects compared to traditional therapies.