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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)

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndrome

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CYAD-02
ENDOXAN
Fludara
Sponsored by
Celyad Oncology SA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic Cancer Center
  • University of Kansas Cancer CenterRecruiting
  • Uz LeuvenRecruiting
  • Chu LiegeRecruiting
  • AZ DELTARecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Dose Escalation Dose Level 1

Dose Escalation Dose Level 2

Dose Escalation Dose Level 3

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Occurrence of Dose Limiting Toxicities as defined per protocol in order to define the final recommended dose.

Secondary Outcome Measures

Full Information

First Posted
November 12, 2019
Last Updated
June 8, 2020
Sponsor
Celyad Oncology SA
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1. Study Identification

Unique Protocol Identification Number
NCT04167696
Brief Title
Study in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients to Determine the Recommended Dose of CYAD-02
Acronym
CYCLE-1
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Recruiting
Study Start Date
November 25, 2019 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
February 2035 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celyad Oncology SA

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Dose escalation
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation Dose Level 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose Escalation Dose Level 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose Escalation Dose Level 3
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
CYAD-02
Intervention Description
CYAD-02 is a Chimeric Antigen Receptor-T (CAR-T) administered after CYFLU.
Intervention Type
Drug
Intervention Name(s)
ENDOXAN
Other Intervention Name(s)
cyclophosphamide
Intervention Description
administered as preconditioning chemotherapy
Intervention Type
Drug
Intervention Name(s)
Fludara
Other Intervention Name(s)
fludarabine
Intervention Description
administered as preconditioning chemotherapy
Primary Outcome Measure Information:
Title
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria (main): 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. 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Frederic LEHMANN, MD, PhD
Phone
003210394100
Email
flehmann@celyad.com
Facility Information:
Facility Name
Mayo Clinic Cancer Center
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohamed Kharfan Dabaja, MD
Phone
904-953-3376
First Name & Middle Initial & Last Name & Degree
Mohamed Kharfan Dabaja, MD
Facility Name
University of Kansas Cancer Center
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tara LIN, MD
Phone
913-945-5052
First Name & Middle Initial & Last Name & Degree
Tara LIN, MD
Facility Name
Uz Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johan MAERTENS, MD
Phone
003216 34 68 80
Email
johan.maertens@uzleuven.be
First Name & Middle Initial & Last Name & Degree
Johan MAERTENS
Facility Name
Chu Liege
City
Liège
ZIP/Postal Code
4000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
YVES BEGUIN, MD
Phone
0032 4 242 52 00
Email
yves.beguin@chuliege.be
First Name & Middle Initial & Last Name & Degree
YVES BEGUIN, MD
Facility Name
AZ DELTA
City
Roeselare
ZIP/Postal Code
8800
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dries DEEREN, MD
Phone
003251 23 73 22
Email
Dries.Deeren@azdelta.be
First Name & Middle Initial & Last Name & Degree
Dries DEEREN, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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