We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT05218408
Previous Study | Return to List | Next Study

CYNK-001 IV and IC in Combination With IL2 in Surgical Eligible Recurrent GBM With IDH-1 Wild Type (CYNK001GBM02)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05218408
Recruitment Status : Recruiting
First Posted : February 1, 2022
Last Update Posted : September 16, 2022
Sponsor:
Information provided by (Responsible Party):
Celularity Incorporated

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)

Condition or disease Intervention/treatment Phase
Astrocytoma, Grade IV Glioblastoma Giant Cell Glioblastoma Glioblastoma Multiforme Biological: CYNK-001 systemic and Intra cavity administration Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/IIa Open Label Multicenter, Non-Randomized, Trial to Assess the Safety and Efficacy of CYNK-001in Combination With Recombinant Human Interleukin-2 in Adults With Recurrent Resection Eligible IDH1 Wild-type Glioblastoma
Actual Study Start Date : March 8, 2022
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1Surgical rGBM CYNK-001 infusion ( IV and IC) in combination with IL-2
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 Phase 1.
Biological: CYNK-001 systemic and Intra cavity administration

Phase 1 Lymphodepletion Days -5,-4 and -3 Cyclophosphamide 900 mg/m2, Fludarabine 30 mg/m2 and Mesna per SOC

IL 2 at 6M IU subcutaneous administration:

For IV cycle ( cycle1) rhIL2 will be administered on Days 1,3,5,8,9,11 and 15 . On days 1, 8 and 15 rhIL-2 will be administered 1 to 3 hours prior to CYNK-001 infusions For IC cycles rhIL2 will be administered 1 to 3 hours prior to each CYNK-001 IC dose.

CYNK-001 : for IV at 2.4 x10^9 or 3.6 x10^9 cells Days 1,8 and 15

Tumor resection will take place 7 to 14 day follow by first IC cycle ( Cycle 2) at 100 Million cells or 200 Million cells

IC cycles 3,4,5 once a week for three weeks , 28 days cycle at100 Million cells or 200 Million cells only for Phase 1 cohort 4 and Phase 2a


Experimental: Phase IIa Surgical rGBM CYNK-001 at MPD IV and IC
To evaluate efficacy and safety of CYNK-001 administrations in recurrent GBM at maximum tolerated dose for IV and IC per Phase 1 outcome. No patients staggering will be implemented in phase 2a. DMC will review the phase 2a entirely
Biological: CYNK-001 systemic and Intra cavity administration

Phase 1 Lymphodepletion Days -5,-4 and -3 Cyclophosphamide 900 mg/m2, Fludarabine 30 mg/m2 and Mesna per SOC

IL 2 at 6M IU subcutaneous administration:

For IV cycle ( cycle1) rhIL2 will be administered on Days 1,3,5,8,9,11 and 15 . On days 1, 8 and 15 rhIL-2 will be administered 1 to 3 hours prior to CYNK-001 infusions For IC cycles rhIL2 will be administered 1 to 3 hours prior to each CYNK-001 IC dose.

CYNK-001 : for IV at 2.4 x10^9 or 3.6 x10^9 cells Days 1,8 and 15

Tumor resection will take place 7 to 14 day follow by first IC cycle ( Cycle 2) at 100 Million cells or 200 Million cells

IC cycles 3,4,5 once a week for three weeks , 28 days cycle at100 Million cells or 200 Million cells only for Phase 1 cohort 4 and Phase 2a





Primary Outcome Measures :
  1. Phase I-Number of patients experience Dose limiting toxicity (DLT) [ Time Frame: 42 days ]
    Defined as the maximum dose safely administered intravenously or Intracavitary for the treatment of patients with GBM

  2. To establish maximum tolerated dose (MTD) and a Recommended Phase 2a Dose (RP2D) [ Time Frame: 42 days ]
    Defined as the number of patients experience Adverse Events and severity

  3. Phase IIa CYNK-001 efficacy [ Time Frame: 6 Months ]
    To evaluate CYNK-001 efficacy post tumor resection and survival within PFS6 Month


Secondary Outcome Measures :
  1. Phase 1-Progression free survival at 6 Months [ Time Frame: 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

  2. Overall survival phase I and IIa [ Time Frame: 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


Other Outcome Measures:
  1. Progression Free survival Phase I and IIa [ Time Frame: 9 and 12 months ]
    is defined as the time from the tumor resection until the date of death 9 and 12 months (PFS9 and PFS12) post tumor resection

  2. Median Progression Free Survival (mPFS) post tumor resection [ Time Frame: 6, 9,12 , 18 and 24 months ]
    is defined as the median 95% CIs time from the tumor resection until the date of death 9 and 12 months (PFS9 and PFS12) post tumor resection

  3. Median Overall Survival (mOS) post tumor resection [ Time Frame: 12 and 24 months ]
    is defined as the median as the 95%CI time from the tumor resection until the date of death.

  4. Time to Progression (TTP) as measured by RANO [ Time Frame: 12 and 24 months ]
    is defined as the time from the tumor resection to the date of first documented disease progression determined in accordance with RANO(iRANO).

  5. Overall Response Rate (ORR) pre and post tumor resection as measured by RANO [ Time Frame: 12 and 24 months ]
    Defined as the proportion of subjects with best overall response of either complete response (CR) or partial response (PR)

  6. Health Quality of Life assessment using European Organization for Research and Treatment of Cancer-30 with Brain20 module scores [ Time Frame: 22, 43, 64,92,120 days ]
    To assess patient quality of life at baseline and post tumor resection surgery per the schedule of Events using EORTC QLQ C30 and EORTC QLQ BN 20 scale

  7. Evaluation of Neurological Assessment of the Neuro Oncology Scale in Glioblastoma (NANO [ Time Frame: 22, 43, 64,92,120 days ]
    NANO scale provides an objective clinician-reported outcome of neurologic function with high inter-observer agreement

  8. Incidence of Treatment Emergent adverse events (TEAE) [ Time Frame: 26 months ]
    any event not present prior to the initiation of the drug treatment

  9. Incidence and Severity of adverse events (AEs) and clinically significant changes in laboratory values [ Time Frame: 26 months ]
    any untoward or unfavorable medical occurrence in patient during the clinical trial



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Exclusion Criteria:

Exclusion Criteria:

  1. Midline shift greater than 0.5 cm or pending herniation.
  2. Patients who were previously treated with Bevacizumab. The use of Bevacizumab for edema or radiation necrosis treatments may be allowed with prior approval from the medical monitor
  3. Anticipated Extent of Resection by volumetric analysis is less than 70%
  4. Patients with greater than two recurrences of GBM are excluded
  5. Patients with any contraindications to MRIs
  6. Treatment with other investigational agents, check point inhibitors and prior immunotherapy such as Vaccine therapy, dendritic cells vaccine within 4 weeks prior to lymphodepletion.
  7. Prior radiation therapy within 12 weeks of screening MRI unless there is unequivocal histological confirmation of tumor progression.
  8. Patients with known disease in the posterior fossa, gliomatous meningitis, extracranial disease or multicentric enhancing disease. Multicentric disease is defined as discrete sites of contrast enhancing disease without contiguous T2/FLAIR abnormality.

    • NOTE: Satellite lesions that are associated with a contiguous area of T2/FLAIR abnormality as the main lesion(s) may be included.

  9. Patients with concurrent use of tumor treating fields (TTF) or laser interstitial thermal therapy (LITT) is excluded. Prior use of TTF or LITT is allowed prior to signing the ICF
  10. Patients with current Carmustine wafers. (Patients that agree to remove the Carmustine wafers at the time of tumor resection during the study are allowed in the study)
  11. Patents who are receiving systemic steroid therapy > 2 mg of dexamethasone or equivalent total dose per day or any other form of immunosuppressive therapy within 5 days of lymphodepletion.

    • Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients requiring physiological doses of steroids (i.e., adrenal insufficiency or hypopituitarism) not to exceed equivalent of dexamethasone 2 mg will not be excluded from the study.

  12. Patients with history of anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome
  13. Active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy.
  14. Any other organ dysfunction (CTCAE Version 5.0 Grade 3 or greater) that will interfere with the administration of the lymphodepletion regimen, rhIL-2, CYNK-001 or the surgical resection as outlined.
  15. Known hypersensitivity to cyclophosphamide, fludarabine, Mesna or rhIL-2.
  16. Have active or clinically significant cardiac disease including:

    • History or presence of serious uncontrolled cardiac arrhythmias.
    • Clinically significant resting bradycardia.
    • Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) <50% or multiple gated acquisition scan (MUGA) <45%.
    • Any of the following within 6 months prior to the start of the study treatments: myocardial infarction (MI), severe/unstable angina, congestive heart failure (CHF), transient ischemic attack (TIA).
  17. Patients with an SaO2 ≤ 92% on room air.

    • Pulmonary Function Tests may be performed during screening for patients with SaO2 ≤ 92% on room air and based on the clinical judgment of the treating physician, patients with an FEV1 ≥ 50% of predicted and DLCO (corrected) of ≥ 40% of predicted may be enrolled.

  18. Has any form of primary immunodeficiency, such as severe combined immunodeficiency disease or acquired immune deficiency syndrome (AIDS).

    • Patients with history of human immunodeficiency virus (HIV) infection must have undetectable HIV ribonucleic acid (RNA).

  19. Known active infection with hepatitis B, hepatitis C or other viral infections requiring systemic therapy.
  20. Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females.
  21. Is Pregnant or breastfeeding.
  22. Received a live vaccine within 30 days prior to lymphodepletion (Day -5).
  23. Any other clinically significant medical disease or condition that, in the Principal Investigator's opinion, may interfere with protocol adherence or the patient's ability to provide informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05218408


Contacts
Layout table for location contacts
Contact: Kevin Berth, B.S 908-373-1898 kevin.berth@Celularity.com
Contact: Mark Awadalla, B.S 908-485-4569 Mark.Awadalla@Celularity.com

Locations
Layout table for location information
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Cara Nolan    626-825-7996    canolan@coh.org   
Principal Investigator: Jana Portnow, MD         
University of California, Irvine Recruiting
Irvine, California, United States, 92697
Contact: Yuna Muyshondt, MPH    949-824-3990    chuny@hs.uci.edu   
Principal Investigator: Daniela Bota, M.D., Ph.D.         
United States, Illinois
Northwestern University Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Cristal Gomez    312-695-9124    cristal.gomez@northwestern.edu   
Principal Investigator: Rimas Lukas, MD         
United States, New Jersey
Hackensack Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Lori Cappello    551-996-5098    lori.cappello@hmhn.org   
Principal Investigator: Samuel Goldlust, MD         
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States, 77030
Contact: Jay Ni    713-792-1496    jni@mdanderson.org   
Principal Investigator: Nazanin Majd, MD         
Sponsors and Collaborators
Celularity Incorporated
Investigators
Layout table for investigator information
Study Director: Mark Awadalla, B.S Celularity inc
Layout table for additonal information
Responsible Party: Celularity Incorporated
ClinicalTrials.gov Identifier: NCT05218408    
Other Study ID Numbers: CYNK-001-GBM-002
First Posted: February 1, 2022    Key Record Dates
Last Update Posted: September 16, 2022
Last Verified: September 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celularity Incorporated:
Interleukin-1
Cyclophosphamide
Fludarabine
immunosuppressive agents
immunological factor
IDH wild type
Surgical GBM
Natural Killer
Cellular Therapy
Allogeneic
Allogeneic stem cell
Ommaya catheter
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue