Clinical trial NCT04489420: Natural Killer Cell (CYNK-001) IV Infusion or IT Administration in Adults With Recurrent GBM
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Astrocytoma, Grade IV
Giant Cell Glioblastoma
Glioblastoma Multiforme
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-infective Agents
Analgesics, Non-narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Keywords: CYNK-001
Glioblastoma Multiforme
Grade IV Astrocytoma
allogeneic
allogeneic stem cell
GBM
cell therapy
Cyclophosphamide
recurrent GBM
recurrent Glioblastoma Multiforme
primary and secondary recurrent GBM
NK cells
natural killer cells
Lead sponsor: Celularity Incorporated
Sponsor class: INDUSTRY
First posted: 2020-07-28
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 2 modalities Systemic vs Intratumoral. For systemic experimental: Cyclophosphamide at Day -3 followed by CYNK-001. On Days 0, 7, and 14. Experimental IntraTumoral, Ommaya placement surgery 7 days prior to CYNK-001 administrations at Days 0, 7 and 14
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants who experienced a Dose-Limiting Toxicity (DLT)
timeFrame: Day 42
measure: Adverse Events (AEs)
timeFrame: 1 year
Secondary outcomes:
measure: Overall Response Rate
timeFrame: 1 year
measure: Duration of Response Rate
timeFrame: 1year
measure: Progression-free survival
timeFrame: 1year
measure: Time to porgression
timeFrame: 1year
measure: Overall Survival
timeFrame: 1year
Other outcomes:
Locations:
city: Houston
country: United States
facility: The Univeristy of Texas MD ANderson Cancer Center
state: Texas
Study officials:
affiliation: Celularity inc.
name: Sharmila Koppisetti, MD
role: STUDY_DIRECTOR
References: