Analgesics, Analgesics, Non-narcotic, Anti-infective Agents, Antiviral Agents, Astrocytoma, Grade IV, Cyclophosphamide, Giant Cell Glioblastoma, Glioblastoma Multiforme, Immunologic Factors, Immunosuppressive Agents, Molecular Mechanisms of Pharmacological Action, Peripheral Nervous System Agents, Physiological Effects of Drugs, Sensory System Agents
Conditions
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
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.
Interventions
BIOLOGICALCYNK001-IV
Planned Starting dose dor IV 1.2x10\^9 cells/dose
BIOLOGICALCYNK001-IT
Planned starting dose for IT 200 x10\^6 +/- 50 x10\^6 cells dose
Sponsors
Celularity Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants who experienced a Dose-Limiting Toxicity (DLT) | Day 42 | Defined as the maximum dose safely administered intravenously or Intratumoral for the treatment of patients with GBM. |
| Adverse Events (AEs) | 1 year | Defined as the number and Severity of Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | 1year | 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 |
| Overall Response Rate | 1 year | Defined as the proportion of subjects with best overall response of either complete response (CR) or partial response (PR) |
| Overall Survival | 1year | Defined as the date of the first CYNK-001 infusion to the date of death |
| Time to porgression | 1year | 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 |
| Duration of Response Rate | 1year | Defined as duration from first observation of partial response (PR) or better to the date of disease progression per RANO criteria |
Countries
United States
Outcome results
None listed