Ignite Creation Date:
2025-12-25 @ 4:06 AM
Ignite Modification Date:
2025-12-26 @ 3:03 AM
Study NCT ID:
NCT03466320
Status:
COMPLETED
Last Update Posted:
2021-05-04
First Post:
2018-02-16
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
DEPLETHINK - LymphoDEPLEtion and THerapeutic Immunotherapy With NKR-2
Sponsor:
Celyad Oncology SA
Organization:
Study Overview
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
Status Verified Date:
2021-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DEPLETHINK
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.
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.
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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: