EPITHINK: Epigenetic Drug Treatment and Therapeutic Immunotherapy With NKR-2

Phase 1

Withdrawn

• Conditions: AML, Adult; Myelodysplastic Syndromes
• Interventions: Biological: NKR-2 CAR-T Cells

• Registration Number: NCT03612739
• Lead Sponsor: Celyad Oncology SA

Brief Summary

This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive chemotherapy or hematopoietic stem cell transplantation.

This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design evaluate. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD.

The study consists of a screening phase, a treatment administration phase and a follow-up phase divided into treatment follow-up (TFU) and long-term safety follow-up (LTSFU). For each patient who received at least one NKR-2 administration, the overall study duration will be 15 years after first NKR-2 administration.

Detailed Description

This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive induction chemotherapy. The treatment consists in six consecutive cycles of AZA, administered at days

1. to 7 of a 28-day cycle. Patients will be treated with 8 injections of NKR-2 at day 9 and 23 of AZA cycles 2-3-4 and 5.

This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD. The study consists of a screening phase, a treatment administration phase and a follow-up phase divided into treatment follow-up (TFU) and long-term safety follow-up (LTSFU). For each patient who received at least one NKR-

2. administration, the overall study duration will be 15 years after first NKR-

2 administration. Patients will be asked to complete a total of 54 visits during the treatment administration phase, and 5 visits during the treatment follow-up phase. During the LTSFU, yearly visits will be scheduled (up to Visit Y15).

Study Timeline

• Study First Submitted: 2018-07-20
• Study First Submitted QC: 2018-07-27
• Study First Posted: 2018-08-02
• Status Verified: 2018-11
• Study Start: 2018-12
• Primary Completion: 2019-05
• Last Update Submitted: 2019-10-25
• Last Update Posted: 2019-10-29
• Study Completion: 2021-08

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1	NKR-2 CAR-T Cells	5-azacytidine + 1x10\^8 NKR-2 CAR-T Cells
Cohort 3	NKR-2 CAR-T Cells	5-azacytidine + 1x10\^9 NKR-2 CAR-T Cells
Cohort 2	NKR-2 CAR-T Cells	5-azacytidine + 3x10\^8 NKR-2 CAR-T Cells

Primary Outcome Measures

Name	Time	Method
The occurrence of Dose Limiting toxicities (DLT) during the study treatment until 6 months after initial treatment.	From Day 1 until the 6 month study visit	The occurrence of DLTs during the study treatment phase (up to month 6)

Secondary Outcome Measures

Name	Time	Method
Additional Safety Endpoint: the occurrence of Adverse Events and Serious Adverse Events and any toxicity linked to study participation until the end of the administration phase, and until the end of the treatment follow-up.	Study enrollment until the 24 month study visit.	The occurrence of AEs and SAES and any toxicity linked to study participation until the end of the administration phase, and until the end of the treatment follow up (Month 24).
Overall Survival (OS) Follow-Up	Study enrollment until the 24 month study visit.	The overall survival (OS), will be evaluated for all patients that received treatment from apheresis until the 24 month study visit.
First Objective Clinical Response	Study enrollment until the 24 month study visit.	The objective clinical response rate (ORR) post the first NKR-2 administration will be evaluated via bone marrow biopsy and aspirate analysis for disease status.
Duration of First Objective Clinical Response	Study enrollment until the 24 month study visit.	The duration of response, for patients that achieve complete response or partial response post the first NKR-2 administration will be evaluated for all patients that receive at least the first dose of NKR-2 infusion.
Second Overall Clinical Response	Study enrollment until the 24 month study visit.	The objective clinical response rate (ORR) post retreatment with NKR-2 administration will be evaluated via bone marrow biopsy and aspirate analysis for disease status.
Relapse-Free Survival (RFS) Follow-Up	Study enrollment until the 24 month study visit.	The Relapse Free Survival (RFS),patients that do not have an event of Progressive disease, will be evaluated for all patients that received treatment from apheresis until the 24 month study visit.
Event Free Survival (EFS) Follow-Up	Study enrollment until the 24 month study visit.	The Event Free Survival (EFS), will be evaluated for all patients that received treatment from apheresis until the 24 month study visit.
Duration of Second Overall Clinical Response	Study enrollment until the 24 month study visit.	The duration of response, for patients that achieve complete response or partial response post the first NKR-2 administration.
Cumulative Incidence of Relapse	Study enrollment until the 24 month study visit.	The cumulative incidence of relapse (CIR), will be evaluated for all patients that are treated with at least one administration of NKR-2
Cumulative Incidence of Death	Study enrollment until the 24 month study visit.	The cumulative incidence of Death (CID), will be evaluated for all patients that are treated with at least one administration of NKR-2
Non-relapse Mortality Rate (NMR)	Study enrollment until the 24 month study visit.	The non-relapse mortality rate (NMR), will be evaluated for all patients that are treated with at least one administration of NKR-2
AML Incidence of Response	Study enrollment until the 24 month study visit.	For AML patients: the incidence of CR, CRMRD-, CRi, MLFS, PR, or SD post NKR-2 administrations until the end of the treatment follow-up (till 24 months after first NKR-2 treatment administration),
MDS Incidence of Response	Study enrollment until the 24 month study visit.	For MDS patients: the incidence of CR, PR, marrow CR, cytogenic response, hematologic improvement or SD post NKR-2 administrations until the end of the treatment follow-up (till 24 months after first NKR-2 treatment administration)
Allogeneic Bone Marrow Transplant	Study enrollment until the 24 month study visit.	The number of patients deemed eligible for an allogeneic stem cell transplantation at screening based on aged and comorbidities by the Investigator who are able to achieve this outcome with investigational treatment.