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

NCT04489420 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: CYNK001-GBM-001
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• 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 (5)

• Overall Response Rate

  1 year

• Duration of Response Rate

  1year

• Progression-free survival

  1year

• Time to porgression

  1year

• Overall Survival

  1year

Study Arms (2)

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

Interventions

CYNK001-IV BIOLOGICAL

Planned Starting dose dor IV 1.2x10\^9 cells/dose

Also known as: CYNK-001 dose level 1 for IV

Intravenous IV ( Recurrent and Surgical ) GBM

CYNK001-IT BIOLOGICAL

Planned starting dose for IT 200 x10\^6 +/- 50 x10\^6 cells dose

Also known as: CYNK-001 dose level 2 for IT

Intratumoral IT ( Recurrent and Surgical ) GBM)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• have an HBV viral load below the limit of quantification and be on viral suppressive therapy
• have current HCV infection, they should be on concurrent HCV treatment and the HCV viral load must be below the limit of quantification
• have a history of HCV infection should have completed curative antiviral treatment and require HCV viral load below the limit of quantification

You may not qualify if:

• 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

Sponsors & Collaborators

• Celularity Incorporated: lead

Study Sites (1)

The Univeristy of Texas MD ANderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Sharmila Koppisetti, MD

  Celularity inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: July 22, 2020
• First Posted: July 28, 2020
• Study Start: October 1, 2020
• Primary Completion: August 10, 2021
• Study Completion: August 10, 2021
• Last Updated: August 10, 2022

Record last verified: 2022-08

Locations

US (1)