Natural Killer Cell (CYNK-001) IV Infusion or IT Administ... | NCT04489420

NCT04489420

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Intravenous IV ( Recurrent and Surgical ) GBM	Experimental	Cohort 1A ( recurrent GBM) will receive CYNK-001 at a dose of 1.2 x 10^9 cells intravenous ( IV) on Days 0, 7, and 14 and will include up to 6 subjects. The subjects will be followed for a 42 day DLT period from the initial CYNK-001 infusion (or 28 days after the last dose). No other treatment interventions are planned between the last day of CYNK-001. In the event of DLTs, Cohort 1C ( recurrent GBM dose-De escalation) will receive CYNK-001 at a dose of 600 x 10^6 cells (IV) on Days 0, 7, 14, and will include up to 6 subjects who will be followed for a 42-day DLT period from the initial CYNK-001 infusion (or 28 days after the last dose. Cohort 1B (surgical cohort) will receive CYNK-001 at the maximum safe dose (MSD) (either 1.2x10^9 cells or 600x10^6 cells) (IV) at Days 0, 7, 14, and will include up to 6 subjects. The tumor resection surgery will be performed after the last CYNK-001 infusion during the DLT period.	Biological: CYNK001-IV
Intratumoral IT ( Recurrent and Surgical ) GBM)	Experimental	The cohort 2A or cohort 2C (recurrent GBM) IT route of administration can be started only after the safety results were acceptable from the completion of cohort 1A or Cohort 1C (IV route of administration). The Treatment Period for the IT cohorts will begin with having the Ommaya catheter placement per institutional policy, which is planned to occur within one week prior to the CYNK-001 administration on Day 0. Cohort 2A will be treated with CYNK-001 IT at 200 x 10^6 ± 50 x 10^6 cells IT on Day 0, 7 and 14 includes up to 6 recurrent GBM subjects Cohort 2C ( dose de-escalation) will be treated with CYNK-001 200 x 106 ± 50 x 106 cells IT on Day 0, and Day 7 ( only two days dosing) and include up to 6 recurrent GBM subjects. Cohort 2B ( the surgical IT cohort) will be treated with CYNK-001 at the maximum safe dose ( MSD) (either 200 x 10^6 ± 50 x 10^6 cells on Days 0, 7 and 14 or at 200 x 10^6 ±50x10^6 cells on Days 0 and 7) and include up to 6 surgical GBM subjects	Biological: CYNK001-IT

Name	Type	Description	Arm Group Labels	Other Names
CYNK001-IV	Biological	Planned Starting dose dor IV 1.2x10^9 cells/dose	Intravenous IV ( Recurrent and Surgical ) GBM

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants who experienced a Dose-Limiting Toxicity (DLT)	Defined as the maximum dose safely administered intravenously or Intratumoral for the treatment of patients with GBM.	Day 42
Adverse Events (AEs)	Defined as the number and Severity of Adverse Events	1 year

Secondary Outcomes

Measure	Description	Time Frame
Overall Response Rate	Defined as the proportion of subjects with best overall response of either complete response (CR) or partial response (PR)	1 year
Duration of Response Rate	Defined as duration from first observation of partial response (PR) or better to the date of disease progression per RANO criteria

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically confirmed glioblastoma multiforme (GBM) and are at first or second relapse.
≥ 18 years of age
Have measurable disease of at least one solitary lesion with a dimension between 1 cm and 5 cm according to RANO
Karnofsky performance status (KPS) ≥ 60
Adequate organ function defined by laboratory values as follows: Creatinine < 140 µmol/L (1.6 mg/dL); if borderline, the creatinine clearance ≥40 mL/min, Bilirubin < 20% above the upper limit of normal, AST and ALT ≤ 2.5 the upper limit of normal.
Absolute Neutrophil count baseline (ANC) ≥1500 cells/uL, Hemoglobin baseline ≥ 9.0 g/dL and Platelets baseline ≥ 100,000 cells/uL prior to the start of study treatment.
Female of childbearing potential (FCBP) must not be pregnant and agree to not becoming pregnant for at least 42 days following the start of the treatment.
Patients with HIV/AIDs are eligible if they have not had an opportunistic infection within the past 12 months
Patients with chronic HBV infection or patients with current or a history of HCV infection are allowed if:
1. have an HBV viral load below the limit of quantification and be on viral suppressive therapy
2. have current HCV infection, they should be on concurrent HCV treatment and the HCV viral load must be below the limit of quantification
3. have a history of HCV infection should have completed curative antiviral treatment and require HCV viral load below the limit of quantification

Exclusion Criteria:

Had prior radiation therapy within 12 weeks of screening MRI unless there is unequivocal histological confirmation of tumor progression
Subjects on growth factors therapy with less than 4 weeks washout period (for short-acting growth factors, such as G-CSF, GM-CSF 5-day wash-out for longer-acting factors (such as Neulasta) 10 days
Radiotherapy, chemotherapy, or other investigational agents within 4 weeks
Prior cellular or gene therapy at any time
Clinical or laboratory signs for immunodeficiency or under immunosuppressive medication or steroids greater than15 mg prednisone or equivalent per day
History of malignancy, other than GBM, unless the subject has been free of disease for > 3 years from the date of signing the ICF. Exceptions include the following noninvasive malignancies: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
Active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy

ID	Term
D001254	Astrocytoma
D005910	Glioma
D018302	Neoplasms, Neuroepithelial
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009375	Neoplasms, Glandular and Epithelial
D009380	Neoplasms, Nerve Tissue