Clinical Trial: NCT04623944 - My Cancer Genome

NCT04623944

Description:

This is a single arm, open-label, multi-center, Phase 1 study to determine safety and tolerability of an experimental therapy called NKX101 (allogeneic CAR NK cells targeting NKG2D ligands) in patients with relapsed/refractory AML or intermediate, high and very high risk relapsed/refractory MDS

Related Conditions:

Acute Myeloid Leukemia
Myelodysplastic Syndromes

Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT04623944

Trial Eligibility

Document

Title

Brief Title: NKX101, Intravenous Allogeneic Engineered Natural Killer Cells, in Adults With AML or MDS
Official Title: A Phase 1 Study of NKX101, an Activating Chimeric Receptor Natural Killer Cell Therapy, in Subjects With Hematological Malignancies or Dysplasias

Clinical Trial IDs

ORG STUDY ID: NKX101-101
NCT ID: NCT04623944

Conditions

Relapsed/Refractory AML
AML, Adult
MDS
Refractory Myelodysplastic Syndromes

Interventions

Drug	Synonyms	Arms
NKX101 - CAR NK cell therapy	Cyclophosphamide, Fludarabine	NKX101 - CAR NK cell therapy

Purpose

Detailed Description

      This is a dose-finding study of NKX101 and will be conducted in 2 parts:

      Part 1: dose finding with two dosing regimens, utilizing modified "3+3" enrollment schema.

      Part 2: dose expansion to further evaluate safety and tolerability, cellular kinetics,
      pharmacodynamics and anti-tumor response in expansion cohorts of patients with either AML or
      MDS.

Trial Arms

Name	Type	Description	Interventions
NKX101 - CAR NK cell therapy	Experimental	All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by 3 or 2 weekly doses of NKX101. Regimen A will dose on Day 0, 7, and 14 of a 28-day cycle. Regimen B will dose on Day 0 and 7 of a 28-day cycle. Part 1: either haplo-matched related donor derived or unrelated off-the-shelf donor derived NKX101 will be used Part 2: either haplo-matched related donor derived or unrelated off-the-shelf donor derived NKX101 will be used	NKX101 - CAR NK cell therapy

Eligibility Criteria

        Inclusion Criteria:

          -  General:

               -  ECOG performance status ≤2

               -  Haplo-matched related subjects require a suitable haplo-matched related donor,
                  who is able and willing to undergo leukapheresis

          -  Disease related:

               -  For AML subjects:

                    -  Previously treated relapsed/refractory AML, including subjects with MRD+
                       disease

                    -  White blood cell count of ≤25 × 10^9/L

               -  For MDS subjects:

                    -  Intermediate-, high-, or very high-risk MDS

                    -  Previously treated relapsed/refractory MDS

          -  Adequate Organ Function

          -  Platelet count ≥30,000/uL (platelet transfusions acceptable)

          -  Other:

               -  Signed informed consent

               -  Agree to use an effective barrier method of birth control

        Exclusion Criteria:

          -  Disease related:

               -  Acute promyelocytic leukemia with t(15;17) (q22;q12); or abnormal promyelocytic
                  leukemia/retinoic acid receptor alpha (APML-RARA)

               -  Evidence of leukemic meningitis or known active central nervous system disease

               -  Use of any anti-AML/MDS chemotherapeutic or targeted small molecule drug within
                  protocol specified window prior to the first dose of NKX101

               -  Presence of residual non-hematologic toxicity from prior therapies that has not
                  resolved to ≤ Grade 1

               -  Any hematopoietic cell transplantation within 16 weeks

          -  Other comorbid conditions and concomitant medications prohibited as per study protocol

          -  Other:

               -  Pregnant or lactating female

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame:	30 days after last dose of NKX101
Safety Issue:
Description:	Incidence, nature, and severity of treatment related adverse events will be evaluated. An adverse event is any unfavorable and unintended sign including clinically significant abnormal laboratory findings, symptom or disease.

Secondary Outcome Measures

Measure:	Assessment of NKX101 half-life
Time Frame:	28 days from first dose of NKX101
Safety Issue:
Description:	Time required for 50% reduction from maximum amount of circulating NKX101

Measure:	NKX101 duration of persistence
Time Frame:	Followed up to 2 years after last dose of NKX101
Safety Issue:
Description:	Testing NKX101 in peripheral blood every 3 months after dosing to determine persistence

Measure:	Evaluation of host immune response against NKX101
Time Frame:	Followed up to 2 years after last dose of NKX101
Safety Issue:
Description:	Serum samples will be measured for antibodies against NKX101

Measure:	Objective response rate to NKX101
Time Frame:	Primary assessment: 28 days after first dose of NKX101 followed up to 2 years after last dose of NKX101
Safety Issue:
Description:	Percentage of subjects with complete and partial response. AML subjects will be assessed for anti-tumor activity of NKX101 based on the updated ELN criteria (Döhner 2017). Subjects with MDS will be assessed for anti-tumor activity of NKX101 based on the IWG criteria with MDS (Cheson 2006).

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Nkarta Inc.

Trial Keywords

NKG2D
CAR
Allogeneic
Natural killer
ACR
NKX101
IL15
Interleukin 15
NK cell
Cell Therapy
Immunotherapy
Adoptive cell therapy
r/r AML
Off-the-shelf

Last Updated

May 17, 2021

Clinical Trials /

NKX101, Intravenous Allogeneic Engineered Natural Killer Cells, in Adults With AML or MDS