What side effects are associated with this type of intervention?

Common treatments for Acute Lymphoblastic Leukemia (ALL) similar to CD19/CD22 CAR T cell therapy include other CAR T cell therapies, chemotherapy, and immunotherapy agents like blinatumomab and inotuzumab ozogamicin. The known side effects of CAR T cell therapies often include cytokine release syndrome (CRS), which can cause fever, low blood pressure, and difficulty breathing, as well as neurotoxicity, which can lead to confusion, seizures, and encephalopathy. Chemotherapy can cause a range of side effects such as nausea, vomiting, hair loss, and increased risk of infections due to bone marrow suppression. Immunotherapy agents like blinatumomab and inotuzumab ozogamicin can also cause CRS, as well as liver toxicity and low blood cell counts.

What prior FDA approvals exist?

The FDA has approved several CAR T cell therapies for the treatment of Acute Lymphoblastic Leukemia (ALL). Tisagenlecleucel (Kymriah) is a CD19-directed genetically modified autologous T cell immunotherapy approved for the treatment of relapsed or refractory B-cell ALL in patients up to 25 years old. Another notable approval is for blinatumomab (Blincyto), a bispecific T cell engager (BiTE) antibody construct that targets CD19 on B cells and CD3 on T cells, facilitating T cell-mediated killing of leukemia cells. These therapies represent significant advancements in the treatment of ALL, leveraging the immune system to target and destroy cancer cells.

What other types of research exist?

Promising novel alternatives to CD19/CD22 CAR T cells for ALL patients include: 1) Bispecific antibodies like blinatumomab, which targets CD3 on T cells and CD19 on B cells, facilitating immune-mediated killing of leukemia cells. 2) Other CAR T cell therapies targeting different antigens such as BCMA, which have shown success in other hematologic malignancies. 3) Novel targeted agents like tyrosine kinase inhibitors (e.g., imatinib, dasatinib) for Philadelphia chromosome-positive ALL. These alternatives are being actively investigated and have shown potential in clinical trials.

← Back to Search

CAR T-cell Therapy

CAR T-Cell Therapy for Acute Lymphoblastic Leukemia

Phase 1

Recruiting

Led By Crystal Mackall

Research Sponsored by Crystal Mackall, MD

Eligibility Criteria Checklist

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

Must have

Diagnosis of ALL with no available alternative curative therapies or subject has declined to pursue alternative therapy; must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, recurred after SCT, or have disease activity that prohibits SCT at the time of enrollment

Recurrence of disease after achieving a complete response (CR)

Must not have

CNS disorders that may impair the ability to evaluate neurotoxicity

Recurrent or refractory ALL limited to isolated testicular

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 15 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies a new treatment combining modified immune cells and chemotherapy for children and young adults with difficult-to-treat leukemia. The immune cells are engineered to target and kill cancer cells, while chemotherapy helps them work more effectively.

Who is the study for?

This trial is for children and young adults aged 1 to 30 with B-cell acute lymphoblastic leukemia that's resistant or has returned after treatment. They should have tried at least two therapies, be free of uncontrolled infections, not pregnant or breastfeeding, and without severe heart conditions. Participants must also have no history of certain other diseases within the last three years.

What is being tested?

The study tests different doses of CD19/CD22 CAR T cells combined with chemotherapy (fludarabine phosphate and cyclophosphamide) in patients whose leukemia expresses CD19 proteins. It aims to find the best dose that is effective while monitoring side effects.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as fever, fatigue, headache, drops in blood pressure; organ inflammation; possible worsening of leukemia symptoms; and risks associated with chemotherapy like nausea, hair loss, mouth sores.

Eligibility Criteria

Inclusion Criteria

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

Select...

I have ALL and can't have or don't want a stem cell transplant.

Select...

My cancer came back after it was completely gone.

Select...

My organs and bone marrow are functioning normally.

Select...

I am between 1 and 30 years old.

Select...

I can do most activities myself if I am over 10, or my child can do most activities if they are 10 or under.

Select...

My cancer cells show high levels of CD19.

Select...

I have Ph+ALL and my condition didn't improve after two treatments, including TKIs.

Select...

My B-ALL cancer did not respond to two different treatments.

Select...

My lymphoma didn't improve or returned after treatment with specific drugs.

Exclusion Criteria

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

Select...

I do not have brain disorders that could affect nerve damage assessment.

Select...

My ALL has come back or didn't respond to treatment, and is only in my testicles.

Select...

I have lymphoma or a disease affecting my brain detected through imaging.

Select...

My white blood cell count is very high or my disease is getting worse quickly.

Select...

I have an infection that isn't controlled or needs IV drugs to manage.

Select...

I have an ongoing infection with HIV, hepatitis B, or hepatitis C.

Select...

I have not had an autoimmune disease or primary immunodeficiency in the last 2 years.

Select...

I am currently on blood thinners.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 15 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 15 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 15 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/CD22 chimeric antigen receptor (CAR) T cells

Rate of successful manufacture and expansion of the CD19/CD22 chimeric antigen receptor (CAR) T cells to satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis (COA)

Secondary study objectives

The ability to achieve a clinical response after administration of CD19/CD22 chimeric antigen receptor (CAR) T cells

Other study objectives

Alterations in early B cell development induced by immune pressure exerted via CD19/CD22-CAR T cells

CD19/CD22 chimeric antigen receptor (CAR) T cell properties

Frequency of CD22+ expression on lymphoma cells

+2 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (CD19/CD22-CAR T cells, chemotherapy)Experimental Treatment5 Interventions

Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and cyclophosphamide IV over 60 minutes on day -2. Patients then receive CD19/CD22-CAR T cells IV over 10-20 minutes on day 0. Patients that benefited from the first dose of CD19/CD22-CAR T cells, had no unacceptable side effects, and have enough cells left over may receive 2 or 3 additional doses of CD19/CD22-CAR T cells.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Fludarabine Phosphate

1997

Completed Phase 3

~2390

0 / 17Eligibility 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 therapies, such as tyrosine kinase inhibitors, block specific molecules involved in cancer cell growth and survival. Immunotherapy, particularly CD19/CD22 CAR T cell therapy, involves genetically engineering a patient's T cells to express receptors that specifically target CD19 and CD22 proteins on leukemia cells, enabling the immune system to recognize and destroy these cancer cells. This matters for ALL patients as it provides a highly targeted treatment option that can be effective in cases where traditional therapies have failed, potentially leading to better outcomes and fewer side effects.