Determining the best dose of CYAD-02 for patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome

Open-label, Phase I, Multi-center Study to Determine in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients the Recommended Dose of CYAD-02 After a Non-myeloablative Preconditioning Chemotherapy Followed by a Potential Consolidation Cycle

This study is testing different doses of a new treatment called CYAD-02 to see which one works best for people with relapsed or hard-to-treat acute myeloid leukemia or myelodysplastic syndrome.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Celyad Oncology SA (industry)
• Drugs / interventions: chemotherapy
• Locations: 5 sites (Jacksonville, Florida and 4 other locations)
• Trial ID: NCT04167696 on ClinicalTrials.gov

What this trial studies

This open-label, phase I, multi-center study aims to find the recommended dose of CYAD-02 in patients with relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Participants will undergo non-myeloablative preconditioning chemotherapy before receiving CYAD-02 infusions. The study will evaluate three dose levels of CYAD-02 using a staggered enrollment approach based on a Fibonacci 3+3 design. Non-progressive patients may receive additional infusions without prior preconditioning. The overall study duration is expected to last approximately 15 years.

Who should consider this trial

Good fit: Ideal candidates include patients with relapsed or refractory AML or high-risk MDS who have failed prior treatments and are not eligible for standard care.

Not a fit: Patients with early-stage AML or MDS who are eligible for standard treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with relapsed or refractory AML or MDS who are not eligible for standard therapies.

How similar studies have performed: Other studies have shown promise with similar approaches in targeting relapsed or refractory hematological malignancies, suggesting potential for success.

Eligibility criteria

Inclusion Criteria (main):

* The patient must not be eligible for standard of care therapy and have one of the following hematological malignancy:

  1. 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.
  2. A confirmed MDS as defined by revised International Prognostic Scoring System criteria for intermediate, high-risk or very high-risk disease or MDS with Tumor Protein 53 mutation as detected by next-generation sequencing, after failure of prior treatment with at least 4 cycles of azacitidine or decitabine defined as:

     * No response to treatment,
     * Loss of response at any time point, or
     * Intolerance to therapy.
* 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.
* The patient must have adequate hepatic and renal functions, as assessed by standard laboratory criteria.
* The patient must have a left ventricular ejection fraction of ≥ 40 %, as determined by echocardiography or a multigated acquisition scan.
* The patient must have a Forced Expiratory Volume (FEV) in the first second /Forced Vital Capacity = 0.7 with FEV-1 at 50 % predicted (GOLD 1 or 2 severity) as determined by spirometry

Exclusion Criteria (main):

* Patients with a confirmed or history of tumor involvement in the central nervous system
* Patients who have received any cancer therapy with therapeutic intent (investigational agent or not)
* Patients with any positive serology test results at baseline
* Patients who plan to receive, are concurrently receiving or have received any investigational agent within 3 weeks before the planned day for the first CYAD-02 infusion
* Patients with uncontrolled intercurrent illness or serious uncontrolled medical disorder
* Patients with significant coagulation disorder or who are receiving treatment with warfarin derivatives, heparin or direct oral anticoagulants
* Patients who have active infections
* Patients with documented history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis and/or active or acute exacerbation of chronic obstructive pulmonary disease

Where this trial is running

Jacksonville, Florida and 4 other locations

• Mayo Clinic Cancer Center — Jacksonville, Florida, United States (NOT_YET_RECRUITING)
• University of Kansas Cancer Center — Fairway, Kansas, United States (RECRUITING)
• Uz Leuven — Leuven, Belgium (RECRUITING)
• Chu Liege — Liège, Belgium (RECRUITING)
• AZ DELTA — Roeselare, Belgium (RECRUITING)

Study contacts

• Study coordinator: Frederic LEHMANN, MD, PhD

Conditions: Acute Myeloid Leukemia, Myelodysplastic Syndrome