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

June 8, 2020 updated by: Celyad Oncology SA

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

27

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
      • Liège, Belgium, 4000
        • Recruiting
        • CHU Liege
        • Contact:
        • Principal Investigator:
          • YVES BEGUIN, MD
      • Roeselare, Belgium, 8800
        • Recruiting
        • AZ Delta
        • Contact:
        • Principal Investigator:
          • Dries DEEREN, MD
  • United States
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Not yet recruiting
        • Mayo Clinic Cancer Center
        • Contact:
          • Mohamed Kharfan Dabaja, MD
          • Phone Number: 904-953-3376
        • Principal Investigator:
          • Mohamed Kharfan Dabaja, MD
    • Kansas
      • Fairway, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Cancer Center
        • Contact:
          • Tara LIN, MD
          • Phone Number: 913-945-5052

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / 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 Names:
  • cyclophosphamide
Drug: Fludara
administered as preconditioning chemotherapy
Other Names:
  • 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 Names:
  • cyclophosphamide
Drug: Fludara
administered as preconditioning chemotherapy
Other Names:
  • 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 Names:
  • cyclophosphamide
Drug: Fludara
administered as preconditioning chemotherapy
Other Names:
  • fludarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
from start the first infusion of CYAD-02 (Day1) up to Day36.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celyad Oncology SA

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 25, 2019

Primary Completion (ANTICIPATED)

December 1, 2021

Study Completion (ANTICIPATED)

February 1, 2035

Study Registration Dates

First Submitted

November 12, 2019

First Submitted That Met QC Criteria

November 14, 2019

First Posted (ACTUAL)

November 19, 2019

Study Record Updates

Last Update Posted (ACTUAL)

June 9, 2020

Last Update Submitted That Met QC Criteria

June 8, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CYAD-02-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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