What side effects are associated with this type of intervention?

Common treatments for Myelodysplastic Syndrome (MDS) include hypomethylating agents like azacitidine and decitabine, which can cause side effects such as neutropenia, thrombocytopenia, anemia, and gastrointestinal symptoms. Thrombopoietin mimetics like romiplostim may increase the risk of progression to acute myeloid leukemia (AML) and cause bone marrow fibrosis. CAR-T cell therapies, such as those targeting NKG2D ligands, are associated with serious toxicities including cytokine-release syndrome, immune effector cell-associated neurotoxicity syndrome, and infections. These side effects highlight the need for careful monitoring and management during treatment.

What prior FDA approvals exist?

The FDA has approved several treatments for Myelodysplastic Syndrome (MDS), including hypomethylating agents such as azacitidine and decitabine, which are commonly used for lower-risk MDS. Additionally, lenalidomide is approved for MDS patients with a deletion 5q cytogenetic abnormality. While CAR-T cell therapies targeting NKG2D ligands, like CYAD-02, are still under investigation, other targeted therapies such as IDH inhibitors (ivosidenib for IDH1 mutations and enasidenib for IDH2 mutations) have been approved for specific genetic mutations in MDS. These treatments aim to manage symptoms, improve quality of life, and potentially extend survival in MDS patients.

What other types of research exist?

Promising novel alternatives to CYAD-02 for MDS patients include: 1) Hypomethylating agents (HMAs) such as azacitidine and decitabine, which have shown comparable efficacy and are well-tolerated. 2) Targeted therapies like ivosidenib for mutant IDH1 and enasidenib for mutant IDH2, which offer a favorable balance of toxicity and efficacy. 3) Combination therapies, such as low-dose cytarabine (LoDAC) combined with venetoclax or glasdegib, which have demonstrated superior outcomes compared to LoDAC monotherapy.

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CAR T-cell Therapy

CYAD-02 for Leukemia/Preleukemia (CYCLE-1 Trial)

Phase 1

Recruiting

Research Sponsored by Celyad Oncology SA

Eligibility Criteria Checklist

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

Must have

The patient must not be eligible for standard of care therapy and have one of the following hematological malignancy: A confirmed relapsed or refractory acute AML (i.e. ≥ 5% blasts in bone marrow or in peripheral blood) with revised European LeukemiaNet (ELN) 2017 risk stratification for favorable, intermediate or adverse groups, after at least one prior therapy defined as either Recurrence of disease after a first complete remission and not eligible for a second course of induction therapy, or Recurrence of disease after a second complete remission, or Failure to achieve a Complete Response after induction chemotherapy.

The patient must have evaluable disease as defined by: Revised Recommendations of the International Working Group (IWG) for Diagnosis, Standardization of Response Criteria for AML patients, IWG 2006 Uniform Response Criteria for patients with MDS. The absolute peripheral blast count should be < 15,000/L.

Must not have

Patients with significant coagulation disorder or who are receiving treatment with warfarin derivatives, heparin or direct oral anticoagulants

Patients with a confirmed or history of tumor involvement in the central nervous system

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Approved for 20 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial tests CYAD-02, a cell-based treatment, in patients with relapsed or refractory AML or MDS who haven't responded to standard treatments. Patients receive mild chemotherapy first, followed by CYAD-02 infusions to target cancer cells. If effective, they may receive additional doses.

Who is the study for?

This trial is for patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who can't have standard treatments. They must have had prior therapy, adequate liver and kidney function, a decent heart pump function, and acceptable lung capacity. Those with high blast counts in blood or central nervous system tumor history are excluded.

What is being tested?

The study tests the safety and optimal dose of CYAD-02 after preconditioning chemotherapy with ENDOXAN and Fludara in AML/MDS patients. It's an early-phase trial aiming to enroll up to 27 participants without dose-limiting toxicities.

What are the potential side effects?

Potential side effects may include reactions related to immune cell infusion such as fever, fatigue, bone pain; effects from chemotherapy like nausea, hair loss; organ inflammation; increased risk of infection due to low blood cell counts.

Eligibility Criteria

Inclusion Criteria

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

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I have a type of blood cancer that has come back or didn’t respond to treatment, and I can't receive standard care.

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My blood cancer can be measured for treatment response, and my blast cell count is below 15,000/L.

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My MDS is intermediate to very high-risk or has TP53 mutation, and I didn't respond to 4 cycles of specific treatments.

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My lung function test shows mild to moderate breathing difficulty.

Exclusion Criteria

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

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I have a serious blood clotting disorder or am on blood thinners.

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My cancer has spread to my brain or spinal cord.

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I have undergone treatment for cancer, whether experimental or approved.

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I have a history of specific lung conditions or flare-ups of chronic lung disease.

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I do not have any serious illnesses that are not under control.

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I currently have an active infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

Approved for 20 Other Conditions

This treatment demonstrated efficacy for 20 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

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: Dose Escalation Dose Level 3Experimental Treatment3 Interventions

in case of no dose limiting toxicity (DLT) and no replacement of patients,3 consecutive patients at the dose of 1x10e9 of CYAD-02 per infusion post preconditioning non-myeloablative chemotherapy according to a 3+3 study design. The preconditioning therapy consists of 3 consecutive days of cyclophosphamide (300 mg/m²/day) and fludarabine (30 mg/m²/day), two days before the CYAD-02 infusion. In case of no progression at D22, the patient is eligible to receive a consolidation cycle of 3 additional CYAD-02 infusion at the same dose level, without prior preconditioning chemotherapy.

Group II: Dose Escalation Dose Level 2Experimental Treatment3 Interventions

in case of no dose limiting toxicity (DLT) and no replacement of patients,3 consecutive patients at the dose of 3x10e8 of CYAD-02 per infusion post preconditioning non-myeloablative chemotherapy according to a 3+3 study design. The preconditioning therapy consists of 3 consecutive days of cyclophosphamide (300 mg/m²/day) and fludarabine (30 mg/m²/day), two days before the CYAD-02 infusion. In case of no progression at D22, the patient is eligible to receive a consolidation cycle of 3 additional CYAD-02 infusion at the same dose level, without prior preconditioning chemotherapy.

Group III: Dose Escalation Dose Level 1Experimental Treatment3 Interventions

in case of no dose limiting toxicity (DLT) and no replacement of patients, 3 consecutive patients at the dose of 1x10e8 of CYAD-02 per infusion post preconditioning non-myeloablative chemotherapy according to a 3+3 study design. The preconditioning therapy consists of 3 consecutive days of cyclophosphamide (300 mg/m²/day) and fludarabine (30 mg/m²/day), two days before the CYAD-02 infusion. In case of no progression at D22, the patient is eligible to receive a consolidation cycle of 3 additional CYAD-02 infusion at the same dose level, without prior preconditioning chemotherapy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fludarabine

FDA approved

0 / 10Eligibility 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 Myelodysplastic Syndrome (MDS) include hypomethylating agents like azacitidine and decitabine, which work by inhibiting DNA methyltransferase, leading to reactivation of tumor suppressor genes and induction of cell differentiation and apoptosis. Immunomodulatory drugs such as lenalidomide modulate the immune response and have anti-angiogenic properties. Erythropoiesis-stimulating agents (ESAs) like erythropoietin promote red blood cell production. CAR-T cell therapies, such as CYAD-02, target NKG2D ligands on malignant cells, enhancing the immune system's ability to recognize and destroy these cells. These treatments are crucial for MDS patients as they address the underlying pathophysiology, improve blood counts, reduce transfusion needs, and potentially modify disease progression.

Mutations in myelodysplastic syndromes: Core abnormalities and CHIPping away at the edges.SOHO State of the Art and Next Questions: Management of Myelodysplastic Syndromes With Deletion 5q.Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.