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

NCT03612739 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: CYAD-N2T-006
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

AML, Adult; Myelodysplastic Syndromes

Keywords

CAR-T Cells; NKR-2; AML; Epigenetic drug therapy

Outcome Measures

Primary Outcomes (1)

• The occurrence of Dose Limiting toxicities (DLT) during the study treatment until 6 months after initial treatment.

  The occurrence of DLTs during the study treatment phase (up to month 6)

  From Day 1 until the 6 month study visit

Secondary Outcomes (14)

• 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.

• Overall Survival (OS) Follow-Up

  Study enrollment until the 24 month study visit.

• Relapse-Free Survival (RFS) Follow-Up

  Study enrollment until the 24 month study visit.

• Event Free Survival (EFS) Follow-Up

  Study enrollment until the 24 month study visit.

• First Objective Clinical Response

  Study enrollment until the 24 month study visit.

Study Arms (3)

Cohort 1

EXPERIMENTAL

5-azacytidine + 1x10\^8 NKR-2 CAR-T Cells

Biological: NKR-2 CAR-T Cells

Cohort 2

EXPERIMENTAL

5-azacytidine + 3x10\^8 NKR-2 CAR-T Cells

Biological: NKR-2 CAR-T Cells

Cohort 3

EXPERIMENTAL

5-azacytidine + 1x10\^9 NKR-2 CAR-T Cells

Biological: NKR-2 CAR-T Cells

Interventions

NKR-2 CAR-T Cells BIOLOGICAL

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.

Also known as: 5-azacytidine (AZA)

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

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

You may not qualify if:

• The patients may not be included in the study if one or more of the following criteria is met:
• Patients with confirmed or history of tumor involvement in the central nervous system (CNS).
• Patients who have received any prior AML/MDS therapy (investigational agent or not).
• Note: Patients are authorized to receive hydroxyurea according to specific conditions as detailed in Section 6.4.
• Patients who are planned to receive, concurrently receiving or have received any investigational agent within 3 weeks before the planned day for the first NKR-2 administration.
• Patients who are under systemic immunosuppressive drugs, unless specific cases authorized per protocol (see Section 6.4).
• Presence of any indwelling catheter or drain (e.g., percutaneous nephrostomy tube, indwelling foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter) may be permissible unless they have a catheter-associated infection that cannot be cleared with antibiotics. Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath, peripherally inserted central catheter, or Hickman catheter are permitted.
• Patients who underwent major surgery within 4 weeks before the planned day for the first NKR-2 administration. Note: Placement of vascular access device is authorized until 10 days before the planned day for the first NKR-2 administration.
• Patients who have received a live vaccine ≤ 6 weeks prior to each NKR-2 administration.
• Patients with uncontrolled intercurrent illness or serious uncontrolled medical disorder including, but not limited to evidence of active pneumonitis on screening chest imaging, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia history (or evidenced after the electrocardiogram planned at screening) and/or pronounced disturbances of the electrical conduction system of the heart, or significant thromboembolic events.
• Patients with significant disorder of coagulation or receiving treatment with warfarin derivatives or heparin.
• Note: Patients receiving systemic individual doses of low molecular weight heparin outside 24 hours prior to each NKR-2 administration are eligible.
• Patients who have active infections including, but not limited to viral, bacterial or fungal infections necessitating use of antibiotics/antivirals/antifungal treatment (prophylaxis is acceptable).
• Patients who are known to be positive or screened positive for hepatitis B (HBsAg positive) or C (anti-HCV positive).
• Patients who are known to be positive or screened positive for the human immunodeficiency virus (HIV).

Sponsors & Collaborators

• Celyad Oncology SA: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Frederic Lehmann, MD

  Celyad SA

  STUDY DIRECTOR

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: 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.

Study Record Dates

• First Submitted: July 20, 2018
• First Posted: August 2, 2018
• Study Start: December 1, 2018
• Primary Completion: May 1, 2019
• Study Completion: August 1, 2021
• Last Updated: October 29, 2019

Record last verified: 2018-11