Astrocytoma, Grade IV, Giant Cell Glioblastoma, Glioblastoma, Glioblastoma Multiforme
Conditions
Keywords
Interleukin-1, Cyclophosphamide, Fludarabine, immunosuppressive agents, immunological factor, IDH wild type, Surgical GBM, Natural Killer, Cellular Therapy, Allogeneic, Allogeneic stem cell, Ommaya catheter
Brief summary
A Phase 1/2a Open Label Multicenter, Non-Randomized, Trial to Assess the Safety and Efficacy of CYNK-001 in Combination with Recombinant Human Interleukin-2 in Adults with Recurrent Resection Eligible IDH1 wild-type Glioblastoma. For phase I portion, the study objectives to assess the safety and feasibility CYNK-001 in combination with rhIL2 of Intravenous (IV) infusion and Intracavitary (IC) administrations following tumor resection and to establish a maximum tolerated dose (MTD) and a Recommended Phase 2a Dose (RP2D) for IV and IC CYNK-001 administration. For Phase IIa, to evaluate efficacy and safety of CYNK-001 administrations in recurrent GBM as measured by Progression Free Survival at 6 months (PFS6M)
Detailed description
This Phase 1/2a, open-label, multicenter, non-randomized study was designed to evaluate the safety, feasibility, and preliminary efficacy of CYNK-001 in combination with recombinant human interleukin-2 (rhIL-2) in adults with recurrent resection-eligible IDH1 wild-type glioblastoma (GBM). The Phase 1 portion was intended to assess the safety and feasibility of intravenous and intracavitary administration of CYNK-001 following tumor resection and to determine the maximum tolerated dose (MTD) and recommended Phase 2a dose (RP2D). The Phase 2a portion was intended to evaluate efficacy and safety, including progression-free survival at 6 months (PFS6M). The study was withdrawn prior to enrollment, and no participants were enrolled or treated.
Interventions
BIOLOGICALCYNK-001 systemic and Intra cavity administration
CYNK-001 administered intravenously and intracavitarily in combination with subcutaneous recombinant human IL-2 following lymphodepleting chemotherapy. The study was designed to evaluate escalating dose levels of CYNK-001 in Phase 1 and the recommended dose in Phase 2a. The study was withdrawn prior to enrollment and no participants were treated.
Sponsors
Celularity Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
he study was designed to include a Phase 1 dose-escalation portion utilizing a 3+3 design followed by a Phase 2a portion evaluating efficacy and safety. The study was withdrawn prior to enrollment and no participants were enrolled.
Intervention model description
The study will contain two phases for the following objectives •The Phase 1 Dose Escalation will utilize a 3+3 dose escalation design and will evaluate safety, feasibility, and preliminary efficacy of four cohort dose levels of CYNK-001 administered after a 6M IU subcutaneous dose of rhIL-2 for both IV and IC cycles. Up to 21 patients will be enrolled over 4 dosing cohorts in Phase1 and 45 patients enrolled for phase IIa. Cohort 4 will be the safety run for Phase IIa. Cohort 4 in its entirety will be reviewed by the DMC prior to starting Phase 2a portion of this study. Phase 2a will continue to explore efficacy and safety of CYNK-001 in combination with rhIL2 in patients with recurrent resection eligible IDH1 wild-type glioblastoma.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be 18 years or older of age on the day of signing informed consent. 2. Have had historical or current histologically confirmed isocitrate dehydrogenase 1(IDH1) wild-type glioblastoma and variants as defined by the World Health Organization 3. Patient must have a T1 weighted 3D MRI with Gadolinium enhancement within 14 days prior to lymphodepletion at Day -5 4. Patient must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted. 5. Radiologically confirmed recurrent glioblastoma at first or second recurrence have contrast enhancing measurable disease with a bidimensional diameter greater than or equal to 10 mm x 10 mm according to RANO and be eligible to undergo tumor resection. 6. Patients must be a candidate to undergo non-emergent surgical resection of the primary target lesion. 7. Multifocal GBM is permissible in the study if there is contiguous T2FLAIR hyperintensity between enhancing lesions on T1 post gadolinium sequences and if in the opinion of the PI surgical resection of the multifocal disease is achievable. • NOTE: Multicentric disease with no demonstrated ventricle communication at the time of screening is excluded. 8. The patient must either be on no steroids or on a stable dose of dexamethasone or equivalent no greater than \> 2 mg a day for at least 5 days prior to lymphodepletion. 9. Karnofsky performance status (KPS) ≥ 60 10. Have washout periods for prior therapies defined as at five half-lives or (4 weeks) prior to the administration of lymphodepletion whichever is shorter 11. Demonstrate at screening adequate organ function by laboratory values as follows: * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L (patient needs to have a minimum of 70 x10\^9/L to undergo resection) * Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2 .5 the upper limit of normal (ULN) * Calculated creatinine clearance ≥ 45.0 mL/minute as estimated by Cockcroft-Gault formula * Total bilirubin ≤ 1.5 x ULN, unless due to Gilbert's syndrome * Total albumin ≥ 3.0 g/dL (30 g/L) * Prothrombin Time (PT) ≤1.5 x ULN unless patient is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulants * activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulants. * Adequate coagulation function defined as INR ≤ 1.5 x ULN, unless the patient is receiving anticoagulant therapy with PT or a PTT/PTT is within therapeutic range. 12. Patients must agree to use a highly effective method of contraception if procreative potential exists from the start of the study until one year after the completion of lymphodepletion for females and 4 months after completion of lymphodepletion for males. * A Female of Childbearing Potential (FCBP) is defined as: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I-Number of patients experience Dose limiting toxicity (DLT) | 42 days | Defined as the maximum dose safely administered intravenously or Intracavitary for the treatment of patients with GBM |
| To establish maximum tolerated dose (MTD) and a Recommended Phase 2a Dose (RP2D) | 42 days | Defined as the number of patients experience Adverse Events and severity |
| Phase IIa CYNK-001 efficacy | 6 Months | To evaluate CYNK-001 efficacy post tumor resection and survival within PFS6 Month |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1-Progression free survival at 6 Months | 6 Months | is defined as the time from the tumor resection to the date of first documented disease progression determined in accordance with RANO (and iRANO) or death due to any reason, whichever occurs first |
| Overall survival phase I and IIa | 6,9 and 12 months | is defined as the time from the tumor resection until the date of death at 6,9 and 12 months |
Contacts
STUDY_DIRECTORsharmila koppisetti, MD
Celularity Incorporated
Outcome results
None listed