What side effects are associated with this type of intervention?

Common treatments for Acute Myelogenous Leukemia (AML), particularly CAR T cell therapies like CD371-YSNVZ-IL18 CAR T cells, are associated with several significant side effects. These include cytokine release syndrome (CRS), which can cause fever, hypotension, and multiorgan dysfunction, and immune effector cell-associated neurotoxicity syndrome (ICANS), which can lead to confusion, seizures, and cerebral edema. Additionally, patients undergoing these treatments are at an increased risk of infections due to the immunosuppressive effects of the therapy.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myelogenous Leukemia (AML), including targeted therapies and chemotherapies. While CAR T-cell therapies have shown promise in hematologic malignancies, their application in AML is still under investigation. Venetoclax, in combination with azacitidine or decitabine, has been approved for newly diagnosed AML in patients ineligible for intensive chemotherapy. Other notable treatments include decitabine and azacitidine for patients unfit for intensive chemotherapy. However, specific CAR T-cell therapies targeting AML, such as the CD371-YSNVZ-IL18 CAR T cells, are still in clinical trial phases and have not yet received FDA approval.

What other types of research exist?

Promising novel alternatives to CD371-YSNVZ-IL18 CAR T cells for AML patients include: 1) Anti-CD123 CAR T cells, which target the CD123 antigen commonly expressed on AML cells. 2) Bispecific T-cell engagers (BiTEs) like AMG 330, which direct T cells to target AML cells expressing CD33. 3) FLT3 inhibitors combined with immunotherapy, targeting the FLT3 mutation present in a subset of AML patients. These therapies have shown potential in recent clinical trials and may offer effective treatment options in 2024.

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CAR T-cell Therapy

CAR T Cell Therapy for Acute Myeloid Leukemia

Q: What is the mechanism of action of this treatment?

The most common treatments for Acute Myelogenous Leukemia (AML) include chemotherapy and immunotherapy. Chemotherapy agents like cytarabine and daunorubicin work by targeting rapidly dividing cells, thereby killing cancerous cells but also affecting normal cells, which can lead to significant side effects. Immunotherapy, particularly Chimeric Antigen Receptor (CAR) T-cell therapy, represents a more targeted approach. CAR T-cells are engineered to express receptors that specifically recognize antigens on AML cells, such as CD371. The addition of IL-18 in the CD371-YSNVZ-IL18 CAR T cells enhances the immune response, potentially improving the efficacy of the treatment. This targeted mechanism is crucial for AML patients as it aims to reduce the leukemia burden while minimizing damage to normal cells, thereby offering a more effective and potentially less toxic treatment option.

Phase 1

Recruiting

Led By Mark Geyer, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

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

Must have

Primary refractory AML: Patients are eligible from disease perspective in the event of failure to achieve a CR, CRh or CRi after one or more of the following regimens:

Age ≥ 16 years: ECOG ≤ 1 or Karnosfsky ≥ 60

Must not have

Pregnant or lactating women; women of childbearing age, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception while receiving study treatment and for at least 12 months after all treatment is finished

Impaired cardiac function (LVEF < 50%) as assessed by ECHO or MUGA scan

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the safety of using specially modified immune cells to treat cancer patients who haven't responded to other treatments. The goal is to find the highest dose that causes few or mild side effects.

Who is the study for?

This trial is for people with a type of blood cancer called Acute Myeloid Leukemia (AML) that has CD371+ expression. It's open to all ages, but kids must be over 1 year old and weigh at least 10kg. Adults need functioning liver and kidneys, no active graft-versus-host disease post-transplant, and can't have had certain treatments recently. Pregnant women or those who could become pregnant must use contraception.

What is being tested?

Researchers are testing a new therapy using special immune cells called CD371-YSNVZ-IL18 CAR T cells to treat AML. They want to find the highest dose that's still safe with few or mild side effects by gradually increasing the amount given to participants.

What are the potential side effects?

While specific side effects aren't listed here, CAR T cell therapies often include symptoms like fever, fatigue, headache, difficulty breathing, rapid heartbeat and low blood pressure which may occur shortly after treatment.

Eligibility Criteria

Inclusion Criteria

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

Select...

My AML did not respond to initial treatment attempts.

Select...

I am 16 or older and can care for myself with minimal assistance.

Select...

I have undergone at least two cycles of treatment combining venetoclax with azacitidine, decitabine, or low-dose cytarabine.

Select...

My AML has returned after treatment or a stem cell transplant.

Select...

My AML has relapsed or is not responding to treatment, and I haven't used all FDA-approved options.

Select...

My kidney function is within the required range for the trial.

Select...

My kidney function is normal for my age.

Select...

My heart's pumping ability is normal or above normal.

Select...

I am under 16 and can do most activities.

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My AML did not fully respond to targeted therapy for its specific mutation.

Select...

I cannot tolerate certain treatments for my advanced leukemia.

Select...

My kidney function, measured by creatinine, is within the normal range.

Select...

My oxygen levels are 92% or higher on room air.

Select...

My AML has returned or is not responding to treatment and tests positive for CD371.

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I have been diagnosed with CD371+ acute myeloid leukemia.

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My AML cancer cells show CD371 presence.

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I have undergone at least two intensive chemotherapy treatments.

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I do not have any signs of ongoing graft-versus-host disease.

Select...

I am receiving CD371-specific CAR T cell therapy.

Select...

I am over 1 year old and weigh more than 10kg.

Select...

I have completed at least 6 cycles of azacitidine or 4 cycles of decitabine.

Exclusion Criteria

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

Select...

I am not pregnant or breastfeeding and if I can become pregnant, I am using effective birth control.

Select...

My heart's pumping ability is below normal.

Select...

I have not had my T cells collected for Part A of the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 6 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Maximum Tolerated Dose (MTD) of CAR T cells

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Step-Down DoseExperimental Treatment1 Intervention

Participants with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Group II: Dose Level 2Experimental Treatment1 Intervention

Participants with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Group III: Dose Level 1Experimental Treatment1 Intervention

Participants with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

0 / 24Eligibility 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 Myelogenous Leukemia (AML) include chemotherapy and immunotherapy. Chemotherapy agents like cytarabine and daunorubicin work by targeting rapidly dividing cells, thereby killing cancerous cells but also affecting normal cells, which can lead to significant side effects. Immunotherapy, particularly Chimeric Antigen Receptor (CAR) T-cell therapy, represents a more targeted approach. CAR T-cells are engineered to express receptors that specifically recognize antigens on AML cells, such as CD371. The addition of IL-18 in the CD371-YSNVZ-IL18 CAR T cells enhances the immune response, potentially improving the efficacy of the treatment. This targeted mechanism is crucial for AML patients as it aims to reduce the leukemia burden while minimizing damage to normal cells, thereby offering a more effective and potentially less toxic treatment option.

Current Limitations and Perspectives of Chimeric Antigen Receptor-T-Cells in Acute Myeloid Leukemia.CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.Harnessing T Cells to Target Pediatric Acute Myeloid Leukemia: CARs, BiTEs, and Beyond.