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

NCT04167696 | Recruiting Phase 1 FDA Drug

• 1 other identifier: CYAD-02-001
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 5

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

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

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

Study Arms (3)

Dose Escalation Dose Level 1

EXPERIMENTAL

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; Drug: ENDOXAN; Drug: Fludara

Dose Escalation Dose Level 2

EXPERIMENTAL

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; Drug: ENDOXAN; Drug: Fludara

Dose Escalation Dose Level 3

EXPERIMENTAL

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; Drug: ENDOXAN; Drug: Fludara

Interventions

CYAD-02 BIOLOGICAL

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

Dose Escalation Dose Level 1; Dose Escalation Dose Level 2; Dose Escalation Dose Level 3

ENDOXAN DRUG

administered as preconditioning chemotherapy

Also known as: cyclophosphamide

Dose Escalation Dose Level 1; Dose Escalation Dose Level 2; Dose Escalation Dose Level 3

Fludara DRUG

administered as preconditioning chemotherapy

Also known as: fludarabine

Dose Escalation Dose Level 1; Dose Escalation Dose Level 2; Dose Escalation Dose Level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Celyad Oncology SA: lead

Study Sites (5)

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

NOT YET RECRUITING

University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

RECRUITING

Uz Leuven

Leuven, 3000, Belgium

RECRUITING

Chu Liege

Liège, 4000, Belgium

RECRUITING

AZ DELTA

Roeselare, 8800, Belgium

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Cyclophosphamide; fludarabine phosphate; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Frederic LEHMANN, MD, PhD

CONTACT

003210394100; flehmann@celyad.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: November 19, 2019
• Study Start: November 25, 2019
• Primary Completion: December 1, 2021
• Study Completion (Estimated): February 1, 2035
• Last Updated: June 9, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); BE (3)