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

NCT ID: NCT04167696

Last Updated: 2020-06-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-25
• Study Completion Date: 2035-02-28

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

CYAD-02

Intervention Type: BIOLOGICAL

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

ENDOXAN

Intervention Type: DRUG

administered as preconditioning chemotherapy

Fludara

Intervention Type: DRUG

administered as preconditioning chemotherapy

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.

Group Type: EXPERIMENTAL

CYAD-02

Intervention Type: BIOLOGICAL

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

ENDOXAN

Intervention Type: DRUG

administered as preconditioning chemotherapy

Fludara

Intervention Type: DRUG

administered as preconditioning chemotherapy

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.

Group Type: EXPERIMENTAL

CYAD-02

Intervention Type: BIOLOGICAL

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

ENDOXAN

Intervention Type: DRUG

administered as preconditioning chemotherapy

Fludara

Intervention Type: DRUG

administered as preconditioning chemotherapy

Interventions

CYAD-02

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

Intervention Type: BIOLOGICAL

ENDOXAN

administered as preconditioning chemotherapy

Intervention Type: DRUG

Fludara

administered as preconditioning chemotherapy

Intervention Type: DRUG

Other Intervention Names

cyclophosphamide; fludarabine

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celyad Oncology SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic Cancer Center

Jacksonville, Florida, United States

Site Status: NOT_YET_RECRUITING

University of Kansas Cancer Center

Fairway, Kansas, United States

Site Status: RECRUITING

Uz Leuven

Leuven, , Belgium

Site Status: RECRUITING

Chu Liege

Liège, , Belgium

Site Status: RECRUITING

AZ DELTA

Roeselare, , Belgium

Site Status: RECRUITING

Countries

United States; Belgium

Central Contacts

Frederic LEHMANN, MD, PhD

Role: CONTACT

flehmann@celyad.com

003210394100

Facility Contacts

Mohamed Kharfan Dabaja, MD

Role: primary

904-953-3376

Tara LIN, MD

Role: primary

913-945-5052

Johan MAERTENS, MD

Role: primary

johan.maertens@uzleuven.be

003216 34 68 80

YVES BEGUIN, MD

Role: primary

yves.beguin@chuliege.be

0032 4 242 52 00

Dries DEEREN, MD

Role: primary

Dries.Deeren@azdelta.be

003251 23 73 22

Other Identifiers

CYAD-02-001

Identifier Type: -

Identifier Source: org_study_id