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
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Celyad Oncology SA
- Enrollment
- 27
- Locations
- 5
- Primary Endpoint
- Occurrence of Dose Limiting Toxicities as defined per protocol in order to define the final recommended dose.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: CYAD-02 (Biological)
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.
Intervention: ENDOXAN (Drug)
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.
Intervention: Fludara (Drug)
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.
Intervention: CYAD-02 (Biological)
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.
Intervention: ENDOXAN (Drug)
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.
Intervention: Fludara (Drug)
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.
Intervention: CYAD-02 (Biological)
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.
Intervention: ENDOXAN (Drug)
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.
Intervention: Fludara (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
No secondary outcomes reported