Back to resultsNatural Killer Cell (CYNK-001) IV Infusion or IT Administration in Adults With Recurrent GBM (CYNK001GBM01)
Primary Purpose
Astrocytoma, Grade IV, Giant Cell Glioblastoma, Glioblastoma Multiforme
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CYNK001-IV
CYNK001-IT
Sponsored by
About this trial
This is an interventional treatment trial for Astrocytoma, Grade IV focused on measuring 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
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:
- 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
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
Sites / Locations
- The Univeristy of Texas MD ANderson Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Intravenous IV ( Recurrent and Surgical ) GBM
Intratumoral IT ( Recurrent and Surgical ) GBM)
Arm Description
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.
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
Outcomes
Primary Outcome Measures
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.
Adverse Events (AEs)
Defined as the number and Severity of Adverse Events
Secondary Outcome Measures
Overall Response Rate
Defined as the proportion of subjects with best overall response of either complete response (CR) or partial response (PR)
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
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
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
Overall Survival
Defined as the date of the first CYNK-001 infusion to the date of death
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04489420
Brief Title
Natural Killer Cell (CYNK-001) IV Infusion or IT Administration in Adults With Recurrent GBM
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
Business decision.
Study Start Date
October 1, 2020 (Actual)
Primary Completion Date
August 10, 2021 (Actual)
Study Completion Date
August 10, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celularity Incorporated
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intravenous IV ( Recurrent and Surgical ) GBM
Arm Type
Experimental
Arm Description
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.
Arm Title
Intratumoral IT ( Recurrent and Surgical ) GBM)
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
CYNK001-IV
Other Intervention Name(s)
CYNK-001 dose level 1 for IV
Intervention Description
Planned Starting dose dor IV 1.2x10^9 cells/dose
Intervention Type
Biological
Intervention Name(s)
CYNK001-IT
Other Intervention Name(s)
CYNK-001 dose level 2 for IT
Intervention Description
Planned starting dose for IT 200 x10^6 +/- 50 x10^6 cells dose
Primary Outcome Measure Information:
Title
Number of Participants who experienced a Dose-Limiting Toxicity (DLT)
Description
Defined as the maximum dose safely administered intravenously or Intratumoral for the treatment of patients with GBM.
Time Frame
Day 42
Title
Adverse Events (AEs)
Description
Defined as the number and Severity of Adverse Events
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
Defined as the proportion of subjects with best overall response of either complete response (CR) or partial response (PR)
Time Frame
1 year
Title
Duration of Response Rate
Description
Defined as duration from first observation of partial response (PR) or better to the date of disease progression per RANO criteria
Time Frame
1year
Title
Progression-free survival
Description
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
Time Frame
1year
Title
Time to porgression
Description
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
Time Frame
1year
Title
Overall Survival
Description
Defined as the date of the first CYNK-001 infusion to the date of death
Time Frame
1year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sharmila Koppisetti, MD
Organizational Affiliation
Celularity inc.
Official's Role
Study Director
Facility Information:
Facility Name
The Univeristy of Texas MD ANderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Natural Killer Cell (CYNK-001) IV Infusion or IT Administration in Adults With Recurrent GBM
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