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Study in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients to Determine the Recommended Dose of CYAD-02 (CYCLE-1)

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ClinicalTrials.gov Identifier: NCT04167696
Recruitment Status : Recruiting
First Posted : November 19, 2019
Last Update Posted : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
Celyad Oncology SA

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myelodysplastic Syndrome Biological: CYAD-02 Drug: ENDOXAN Drug: Fludara Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 25, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : February 2035


Arm Intervention/treatment
Experimental: Dose Escalation Dose Level 1

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.

Biological: CYAD-02
CYAD-02 is a Chimeric Antigen Receptor-T (CAR-T) administered after CYFLU.

Drug: ENDOXAN
administered as preconditioning chemotherapy
Other Name: cyclophosphamide

Drug: Fludara
administered as preconditioning chemotherapy
Other Name: fludarabine

Experimental: Dose Escalation Dose Level 2

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.

Biological: CYAD-02
CYAD-02 is a Chimeric Antigen Receptor-T (CAR-T) administered after CYFLU.

Drug: ENDOXAN
administered as preconditioning chemotherapy
Other Name: cyclophosphamide

Drug: Fludara
administered as preconditioning chemotherapy
Other Name: fludarabine

Experimental: Dose Escalation Dose Level 3

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.

Biological: CYAD-02
CYAD-02 is a Chimeric Antigen Receptor-T (CAR-T) administered after CYFLU.

Drug: ENDOXAN
administered as preconditioning chemotherapy
Other Name: cyclophosphamide

Drug: Fludara
administered as preconditioning chemotherapy
Other Name: fludarabine




Primary Outcome Measures :
  1. 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. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04167696


Contacts
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Contact: Frederic LEHMANN, MD, PhD 003210394100 flehmann@celyad.com

Locations
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United States, Florida
Mayo Clinic Cancer Center Not yet recruiting
Jacksonville, Florida, United States, 32224
Contact: Mohamed Kharfan Dabaja, MD    904-953-3376      
Principal Investigator: Mohamed Kharfan Dabaja, MD         
United States, Kansas
University of Kansas Cancer Center Recruiting
Fairway, Kansas, United States, 66205
Contact: Tara LIN, MD    913-945-5052      
Principal Investigator: Tara LIN, MD         
Belgium
Uz Leuven Recruiting
Leuven, Belgium, 3000
Contact: Johan MAERTENS, MD    003216 34 68 80    johan.maertens@uzleuven.be   
Principal Investigator: Johan MAERTENS         
Chu Liege Recruiting
Liège, Belgium, 4000
Contact: YVES BEGUIN, MD    0032 4 242 52 00    yves.beguin@chuliege.be   
Principal Investigator: YVES BEGUIN, MD         
AZ DELTA Recruiting
Roeselare, Belgium, 8800
Contact: Dries DEEREN, MD    003251 23 73 22    Dries.Deeren@azdelta.be   
Principal Investigator: Dries DEEREN, MD         
Sponsors and Collaborators
Celyad Oncology SA
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Responsible Party: Celyad Oncology SA
ClinicalTrials.gov Identifier: NCT04167696    
Other Study ID Numbers: CYAD-02-001
First Posted: November 19, 2019    Key Record Dates
Last Update Posted: June 9, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites