Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 4:06 AM
Ignite Modification Date:
2025-12-25 @ 4:06 AM
NCT ID:
NCT03466320
Brief 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.
Detailed 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.
Study:
NCT03466320
Study Brief:
Protocol Section:
NCT03466320