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.
Recruiting
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| CYAD-02 | Dose Escalation Dose Level 1 | |
| ENDOXAN | cyclophosphamide | Dose Escalation Dose Level 1 |
| Fludara | fludarabine | Dose Escalation Dose Level 1 |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | 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. |
| Safety Issue: | |
| Description: |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Celyad Oncology SA |
June 9, 2020
