DEPLETHINK - LymphoDEPLEtion and THerapeutic Immunotherapy With NKR-2 — DEPLETHINK  

AML Clinical Trial

Official title: An Open-label, Phase I/II Study to Assess the Safety and Clinical Activity of NKR-2 Treatment Administration After a Non-myeloablative Preconditioning Chemotherapy in Relapse/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients.

Status Completed

Clinical Trial Summary

This open-label Phase I study aims at assessing primarily the safety of the NKR-2 treatment administered after a non-myeloablative preconditioning regimen in r/r AML/MDS patients.

This Phase I study will contain two different sequential segments. The first segment will determine the recommended investigational treatment option (schedule of preconditioning and NKR-2 dose) and the second segment will expand to a larger number of r/r AML/MDS patients.

Clinical Trial Description

This open-label Phase I/II study aims at assessing primarily the safety and the clinical activity of the NKR-2 treatment administered after a non-myeloablative preconditioning regimen in r/r AML/MDS patients.

The Phase I part of the study will contain two different sequential segments. The first segment (dose escalation segment) will determine the recommended investigational treatment option (schedule of preconditioning and NKR-2 dose) and the second segment (extension segment) will expand to a larger number of r/r AML/MDS patients.

The Phase II part of the study will also contain two sequential segments, assessing the clinical activity of the NKR-2 treatment administrated as per the recommended investigational treatment option (schedule of preconditioning and NKR-2 dose).

The Phase I dose escalation segment will evaluate the preconditioning regimen consisting in cyclophosphamide 300 mg/m² and fludarabine 30 mg/m² daily (CYFLU) administrated 3 consecutive days at a specific interval prior to the NKR 2 administration. This segment is divided into four sequential cohorts to evaluate respectively:

• Two different intervals between the preconditioning regimen and the NKR-2 administration i.e. NKR-2 administered 3 days (T3) or 7 days (T7) after the end of the preconditioning regimen,

• Three different NKR-2 dose-levels i.e. dose-level 1 (1x108 NKR 2/injection), dose-level 2 (3x108 NKR-2/injection) and dose-level 3 (1x109 NKR-2/injection).

The Phase I extension segment will enroll more r/r AML/MDS patients (to reach 9 evaluable patients in total) to further evaluate the recommended NKR-2 dose (1x108, 3x108 or 1x109 NKR-2/injection) administered at the recommended interval (T3 or T7) after the CYFLU preconditioning.

The Phase II will enroll more r/r AML/MDS patients (13 patients in total in the segment 1 and 30 new patients in the segment 2) to further evaluate the recommended NKR-2 dose (1x108, 3x108 or 1x109 NKR-2/injection) administered at the recommended interval (T3 or T7) after the CYFLU preconditioning to assess the clinical activity.

Each patient will receive a single administration of NKR-2 following the preconditioning regimen. Depending on the clinical response as evaluated at the first tumor assessment, scheduled three weeks after NKR-2 administration, three situations may arise:

• If the patient is presenting a complete remission, partial remission, or stable disease, and meets all criteria for a consolidation cycle, then three new injections of NKR-2 at the recommended dose defined in the ongoing THINK study (THINK RecD), without prior preconditioning, will be administered with a two weeks interval,

• If the patient is in PD, or does not meet all criteria for the consolidation cycle he/she will not receive any other NKR-2 injection but will follow other visits as scheduled.

For each patient who received at least one NKR-2 administration, the overall study duration will be 15 years after first NKR-2 administration.

The duration of the administration phase and treatment follow-up will be 24 months.

Patients will be asked to complete a total of maximum 20 visits during the treatment administration phase, and maximum 6 visits during the treatment follow-up phase. During the long-term safety follow-up, yearly visits will be scheduled (up to Y15).

Rationale for the study:

NKR-2 has the potential to treat many distinct tumor-types because of a broad expression and important prevalence of the NKG2D ligands expression in various tumor types including in r/r AML/MDS. This Phase I study will explore the hypothesis that the administration of modified T-cells targeting NKG2D-ligands expressed by AML/MDS cells, after a prior nonmyeloablative preconditioning treatment, in patients refractory to and/or relapsing after prior therapies, is safe and, considering the poor outcomes and lack of therapeutic strategies for this patient population, may have a strategic advantage over current approaches and provide potential clinical benefit.

Objectives of the study:

Primary

To document and characterize:

• The safety of the NKR-2 treatment administration in r/r AML/MDS patients after a non-myeloablative preconditioning. (Phase I part)

• The objective response rate (ORR) post the first NKR-2 administration. (Phase II part)

Secondary

To document and characterize:

• The NKR-2 peripheral blood kinetics post-administration,

• Indicators of clinical activity,

• Additional indicators of safety. ;

Related Conditions & MeSH terms

• AML
• MDS

• NCT number: NCT03466320
• Study type: Interventional
• Source: Celyad Oncology SA
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 18, 2018
• Completion date: February 1, 2021