Astrocytoma, Grade IVPhase 1CYNK001GBM01NCT04489420
Natural Killer Cell (CYNK-001) IV Infusion or IT Administration in Adults With Recurrent GBM
A Phase 1 study testing CYNK001-IV and CYNK001-IT in people with Astrocytoma, Grade IV and Giant Cell Glioblastoma, run by Celularity Incorporated at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Astrocytoma, Grade IV, Giant Cell Glioblastoma, Glioblastoma Multiforme
- What is being tested?
- CYNK001-IV and CYNK001-IT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2020to 10 Aug 2021
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
The Univeristy of Texas MD ANderson Cancer Center
Houston, Texas, 77030
About this study
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)
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
- Being tested
- CYNK001-IV, CYNK001-IT
- 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
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYNK001-IVBiological
Also called CYNK-001 dose level 1 for IV
Planned Starting dose dor IV 1.2x10^9 cells/dose
CYNK001-ITBiological
Also called CYNK-001 dose level 2 for IT
Planned starting dose for IT 200 x10^6 +/- 50 x10^6 cells dose
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Biological: CYNK001-IT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 42
Adverse Events (AEs)
Defined as the number and Severity of Adverse Events
Measured: 1 year
Secondary outcomes (5)
Overall Response Rate
Defined as the proportion of subjects with best overall response of either complete response (CR) or partial response (PR)
Measured: 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
Measured: 1year
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
Measured: 1year
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
Measured: 1year
Overall Survival
Defined as the date of the first CYNK-001 infusion to the date of death
Measured: 1year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2020
- Study start1 Oct 2020
- Primary completion10 Aug 2021
- Study completion10 Aug 2021
Why it stopped: Business decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Astrocytoma, Grade IVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celularity Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sharmila Koppisetti, MD, Study director, Celularity inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04489420
- Sponsor's protocol ID
- CYNK001-GBM-001
- Acronym
- CYNK001GBM01
- Status last verified
- Aug 2022
- First submitted
- 22 Jul 2020
- Last updated
- 10 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided