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Study in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients to Determine the Recommended Dose of CYAD-02

NCT04167696

Description:

An open-label, phase I, multi-center study to determine in relapsed/refractory (r/r) acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients the recommended dose of CYAD‑02 after a non-myeloablative preconditioning chemotherapy followed by a potential CYAD‑02 consolidation cycle for non-progressive patient. A maximum of 27 r/r AML/MDS patients will be evaluated in this study in case of no dose limiting toxicity (DLT) and no replacement of patients.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Study in Relapsed/Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) Patients to Determine the Recommended Dose of the Investigational Product (CYAD-02)
  • Official Title: An 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 CYAD-02 Consolidation Cycle for Non-progressive Patients

Clinical Trial IDs

  • ORG STUDY ID: CYAD-02-001
  • NCT ID: NCT04167696

Conditions

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
CYAD-02Dose Escalation Dose Level 1
ENDOXANcyclophosphamideDose Escalation Dose Level 1
FludarafludarabineDose Escalation Dose Level 1

Purpose

An open-label, phase I, multi-center study to determine in relapsed/refractory (r/r) acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients the recommended dose of CYAD‑02 after a non-myeloablative preconditioning chemotherapy followed by a potential CYAD‑02 consolidation cycle for non-progressive patient. A maximum of 27 r/r AML/MDS patients will be evaluated in this study in case of no dose limiting toxicity (DLT) and no replacement of patients.

Detailed Description

      This open-label phase I, multi-center study aims 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 CYAD-02 consolidation
      cycle for non-progressive patients.

      During dose escalation, three prespecified dose-levels of CYAD-02 will be evaluated in three
      cohorts. Patient enrollment during dose-escalation will be staggered according to the
      Fibonacci 3+3 design and extension of cohorts II and III will be done in parallel. The first
      CYAD-02 infusion will be administered after prior non-myeloablative preconditioning
      chemotherapy (CYFLU) administered on three consecutive days.

      Non-progressive patients meeting the criteria specified below may receive a consolidation
      cycle with three additional CYAD-02 infusions at a 2-week interval without prior
      preconditioning.

      For all patients who received at least one CYAD-02 infusion, the overall study duration will
      be approximately 15 years.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Dose Level 1Experimentalin 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.
  • CYAD-02
  • ENDOXAN
  • Fludara
Dose Escalation Dose Level 2Experimentalin 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.
  • CYAD-02
  • ENDOXAN
  • Fludara
Dose Escalation Dose Level 3Experimentalin 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.
  • CYAD-02
  • ENDOXAN
  • Fludara

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Occurrence of Dose Limiting Toxicities as defined per protocol in order to define the final recommended dose.
Time Frame:from start the first infusion of CYAD-02 (Day1) up to Day36.
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Celyad (formerly named Cardio3 BioSciences)

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