Natural Killer Cell (CYNK-001) IV Infusion or IT Administration in Adults With Recurrent GBM

Glioblastoma Multiforme Clinical Trial

— CYNK001GBM01  

Official title:

A Phase I Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK-001) in Adults With Recurrent Glioblastoma Multiforme (GBM)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04489420
• Other study ID #: CYNK001-GBM-001
• Status: Terminated
• Phase: Phase 1
• Start date: October 1, 2020
• Est. completion date: August 10, 2021

Study information

• Verified date: August 2022
• Source: Celularity Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will find the maximum safe dose (MSD) or maximum tolerated dose (MTD) of CYNK-001 which are NK cells derived from human placental CD34+ cells and culture-expanded. CYNK-001 cells will be given after lymphodepleting chemotherapy for the systemic cohort (IV) (intravenous). The intratumoral cohort (IT) will not be giving lymphodepletion. The safety of this treatment will be evaluated, and researchers want to learn if NK cells will help in treating recurrent glioblastoma multiforme.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: August 10, 2021
• Est. primary completion date: August 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed glioblastoma multiforme (GBM) and are at first or second relapse.

2. = 18 years of age

3. Have measurable disease of at least one solitary lesion with a dimension between 1 cm and 5 cm according to RANO

4. Karnofsky performance status (KPS) = 60

5. 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.

6. 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.

7. 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.

8. Patients with HIV/AIDs are eligible if they have not had an opportunistic infection within the past 12 months

9. 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:

1. Had prior radiation therapy within 12 weeks of screening MRI unless there is unequivocal histological confirmation of tumor progression

2. 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

3. Radiotherapy, chemotherapy, or other investigational agents within 4 weeks

4. Prior cellular or gene therapy at any time

5. Clinical or laboratory signs for immunodeficiency or under immunosuppressive medication or steroids greater than15 mg prednisone or equivalent per day

6. 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)

7. Active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy

Related Conditions & MeSH terms

• Analgesics
• Analgesics, Non-narcotic
• Anti-infective Agents
• Antiviral Agents
• Astrocytoma
• Astrocytoma, Grade IV
• Cyclophosphamide
• Giant Cell Glioblastoma
• Glioblastoma
• Glioblastoma Multiforme
• Immunologic Factors
• Immunosuppressive Agents
• Molecular Mechanisms of Pharmacological Action
• Peripheral Nervous System Agents
• Physiological Effects of Drugs
• Sensory System Agents

Intervention

Biological:
• CYNK001-IV
Planned Starting dose dor IV 1.2x10^9 cells/dose
• CYNK001-IT
Planned starting dose for IT 200 x10^6 +/- 50 x10^6 cells dose

Locations

Country	Name	City	State
United States	The Univeristy of Texas MD ANderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Celularity Incorporated

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Adverse Events (AEs)	Defined as the number and Severity of Adverse Events	1 year
Secondary	Overall Response Rate	Defined as the proportion of subjects with best overall response of either complete response (CR) or partial response (PR)	1 year
Secondary	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	1year
Secondary	Progression-free survival	Defined as date of the first CYNK-001 infusion to the date of disease progression per RANO Response Criteria or death (regardless of cause of death), whichever comes first	1year
Secondary	Time to porgression	Defined as the date of the first CYNK-001 infusion to the date of disease progression per RANO Response Criteria, with deaths from causes other than progression censored	1year
Secondary	Overall Survival	Defined as the date of the first CYNK-001 infusion to the date of death	1year