What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) that involve genetically modified T cells, such as CAR-T cell therapies, can have several side effects. These include cytokine release syndrome (CRS), which may cause fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing. Neurotoxicity is another significant side effect, potentially leading to confusion, seizures, and severe headaches. Additionally, there is an increased risk of infections due to the immunosuppressive nature of the treatment, as well as potential off-target effects where the modified T cells attack healthy tissues.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myeloid Leukemia (AML), including targeted therapies and immunotherapies. Gemtuzumab ozogamicin, an anti-CD33 monoclonal antibody-drug conjugate, is one such targeted therapy approved for relapsed AML. Additionally, the FDA has approved CAR-T cell therapies for other hematologic malignancies, such as brexucabtagene autoleucel for mantle cell lymphoma, which is similar in concept to the genetically modified T cells being studied in the DARIC trial. These therapies represent significant advancements in the treatment of AML and related conditions.

What other types of research exist?

Promising novel alternatives for AML treatment in 2024 include hypomethylating agents (HMAs) such as azacitidine and decitabine, which have shown comparable efficacy and tolerability. Additionally, targeted therapies like ivosidenib for mutant IDH1 and enasidenib for mutant IDH2 are promising options. Immunotherapy strategies, including genetically engineered NK cells with enhanced CD38-directed antitumor activity, also hold potential.

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CAR T-cell Therapy

SC-DARIC33 CAR T Cells for Acute Myeloid Leukemia

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

Common treatments for Acute Myeloid Leukemia (AML) include chemotherapy, hypomethylating agents, and immunotherapies. Chemotherapy, such as the combination of cytarabine and daunorubicin, works by killing rapidly dividing cells, including leukemic blasts. Hypomethylating agents like azacitidine and decitabine inhibit DNA methylation, leading to reactivation of tumor suppressor genes and induction of cancer cell death. Emerging immunotherapies, such as CAR-T cells, involve genetically modifying a patient's T cells to express receptors that specifically target and kill AML cells. The DARIC T cell product is a novel approach where T cells are engineered to express a Dimerizing Agent Regulated Immunoreceptor Complex, enhancing their ability to recognize and destroy AML cells. These mechanisms are crucial for AML patients as they offer targeted and potentially more effective treatment options, especially for those with relapsed or refractory disease.

Phase 1

Recruiting

Research Sponsored by Seattle Children's Hospital

Eligibility Criteria Checklist

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

Must have

Performance status score of Lansky ≥ 50 for subjects <16 years of age or Karnofsky score ≥ 50 for subjects ≥ 16 years

AML that expresses CD33 by flow cytometry and meets specific criteria including relapse of AML, refractory AML, or evidence of AML re-emergence post HCT detectable by flow cytometry

Must not have

Prior virotherapy

Presence of active severe infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 28 days

Awards & highlights

Summary

This trial tests a new treatment using a patient's own enhanced immune cells to fight hard-to-treat leukemia in young patients. The modified cells are designed to better detect and destroy cancer cells when activated by a special agent. This approach has shown remarkable results in treating young patients with acute lymphoblastic leukemia (ALL) and adults with lymphoma and multiple myeloma.

Who is the study for?

This trial is for pediatric and young adult patients up to 30 years old with relapsed or refractory CD33+ acute myeloid leukemia (AML). They must have adequate organ function, not be pregnant or breastfeeding, agree to use effective contraception, and be able to undergo apheresis. Those with active severe infections, other cancers, primary immunodeficiency syndrome, or who can't tolerate lymphodepleting regimens are excluded.

What is being tested?

The study tests SC-DARIC33 CAR T cells in children and young adults with AML that's come back after treatment or hasn't responded at all. It's an early-phase trial assessing the safety of using genetically modified T cells designed to target cancerous cells expressing CD33.

What are the potential side effects?

While specific side effects aren't listed here, CAR T cell therapies like SC-DARIC33 may cause symptoms such as fever, fatigue, headache, difficulty breathing, rapid heartbeat and low blood pressure. Some people might experience more serious issues affecting the brain or immune system.

Eligibility Criteria

Inclusion Criteria

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

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I can do most activities but may need help, regardless of my age.

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My AML shows CD33 and has relapsed or is not responding to treatment.

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I can undergo apheresis or have enough T cells for treatment production.

Exclusion Criteria

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

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I have had virotherapy before.

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I am currently suffering from a severe infection.

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I have a cancer diagnosis that is not acute myeloid leukemia.

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I cannot take rapamycin due to health reasons.

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I have or had brain or spinal cord disease that needed treatment.

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My brain or spinal cord leukemia symptoms can't be managed before getting DARIC T cell treatment.

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.

Primary study objectives

Ability to successfully manufacture SC-DARIC33

Adverse events associated with SC-DARIC33 cell product infusions will be assessed

Secondary study objectives

Acute Myeloid Leukemia response to SC-DARIC in subjects with relapsed or refractory CD33+ myeloid leukemia will be assessed

Trial Design

1Treatment groups

Experimental Treatment

Group I: DARIC-33Experimental Treatment1 Intervention

0 / 9Eligibility 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

Common treatments for Acute Myeloid Leukemia (AML) include chemotherapy, hypomethylating agents, and immunotherapies. Chemotherapy, such as the combination of cytarabine and daunorubicin, works by killing rapidly dividing cells, including leukemic blasts. Hypomethylating agents like azacitidine and decitabine inhibit DNA methylation, leading to reactivation of tumor suppressor genes and induction of cancer cell death. Emerging immunotherapies, such as CAR-T cells, involve genetically modifying a patient's T cells to express receptors that specifically target and kill AML cells. The DARIC T cell product is a novel approach where T cells are engineered to express a Dimerizing Agent Regulated Immunoreceptor Complex, enhancing their ability to recognize and destroy AML cells. These mechanisms are crucial for AML patients as they offer targeted and potentially more effective treatment options, especially for those with relapsed or refractory disease.

Current Limitations and Perspectives of Chimeric Antigen Receptor-T-Cells in Acute Myeloid Leukemia.Targeting of a B7-1 (CD80) immunoglobulin G fusion protein to acute myeloid leukemia blasts increases their costimulatory activity for autologous remission T cells.