ADCTA for Adjuvant Immunotherapy in Standard Treatment of Recurrent Glioblastoma Multiforme (GBM)

NCT ID: NCT04277221

Last Updated: 2020-03-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-19
• Study Completion Date: 2022-12-31

Brief Summary

To confirm the result of previous Phase I/II and phase II clinical trials, this trial is to test the efficacy and safety of ADCTA immunotherapy plus the standard therapy in comparison with standard therapy alone in patients with recurrent GBM.

Conditions

Glioblastoma Multiforme

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard therapy with ADCTA vaccine (study group)

• ADCTA vaccine as study treatment

Dose(s): Ten doses, including 2~4×10^7 cells for the 1st dose (double doses), and 1~2×10^7cells for the 2nd to 10th doses.

Administrative route: The ADCTA vaccine will be injected in axillar or inguinal regions close to lymphnodes subcutaneously at clinic.

Frequency: The primary immunization inoculation is followed by 3 vaccines bi-weekly and then 6 vaccines monthly inoculation, for a total of 10 doses.

• Bevacizumab as standard therapy

Group Type: EXPERIMENTAL

Autologous Dendritic Cell/Tumor Antigen, ADCTA

Intervention Type: BIOLOGICAL

ADCTA is an individualized cell immunotherapy co-culturing autologous dendritic cells derived from peripheral blood mononuclear cells (PBMNCs) with autologous tumor cell as antigen in order to evoke specific immune response.

Standard therapy (control group)

• No study treatment
• Bevacizumab as standard therapy

Group Type: ACTIVE_COMPARATOR

Autologous Dendritic Cell/Tumor Antigen, ADCTA

Intervention Type: BIOLOGICAL

ADCTA is an individualized cell immunotherapy co-culturing autologous dendritic cells derived from peripheral blood mononuclear cells (PBMNCs) with autologous tumor cell as antigen in order to evoke specific immune response.

Interventions

Autologous Dendritic Cell/Tumor Antigen, ADCTA

ADCTA is an individualized cell immunotherapy co-culturing autologous dendritic cells derived from peripheral blood mononuclear cells (PBMNCs) with autologous tumor cell as antigen in order to evoke specific immune response.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Specimen collection screening

• Karnofsky performance status (KPS) ≥ 60 at assessment prior to surgery
• ≥ 18 and ≤ 70 years of age
• Subject has been diagnosed with GBM and has undergone resection surgery followed by standard brain RT + concurrent temozolomide and adjuvant temozolomide, and progression occurred. The foregoing progression is defined as when patients with primary GBM experience an image or clinical deterioration after receiving standard of care.
• Contrast-enhanced MRI suspects recurrent GBM
• Supratentorial tumor
• Must voluntarily sign and date informed consent form for specimen acquisition and future use, for study screening, approved by an Independent Ethics Committee (IEC)/ Institutional Review Board (IRB), prior to the initiation of any study-specific procedures

2. Study screening

• Karnofsky performance status (KPS) ≥ 60 at randomization
• Submission of fresh tumor
• Post-operation contrast-enhanced MRI scan must be done after surgical resection, with the intent for cyto-reduction ≥ 80% of the contrast-enhancing tumor mass
• Histologically confirmed WHO grade IV glioma by pathology tissue screening
• Subjects receiving bevacizumab as standard of care for given indication
• Subject has adequate bone marrow, renal, and hepatic function prior to randomization as follow:

1. White blood cell (WBC) count ≥ 2,000/mm^3;

2. Absolute neutrophil count (ANC) ≥ 1,000/mm^3;

3. Platelets ≥ 100,000/mm^3;

4. Hemoglobin (Hgb) ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable.);

5. Blood Urea Nitrogen (BUN) < 30 mg/dL;

6. Creatinine < 2 mg/dL;

7. Renal function: calculated creatinine clearance ≥ 30 mL/min;

8. Hepatic function: Total bilirubin ≤ 3 times upper limit of normal (ULN), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2 times ULN;

9. Prothrombin Time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6 times ULN unless therapeutically warranted.

• Subjects with recurrent GBM (Grade IV) are eligible for this protocol. An independent neuropathologist will review this diagnosis during the enrollment process
• Must voluntarily sign and date informed consent form, for study participation, approved by an Independent Ethics Committee (IEC)/ Institutional Review Board (IRB), prior to the initiation of any study-specific procedures

Exclusion Criteria

1. Specimen collection screening

• Multifocal GBM
• Prior invasive malignancy (except for non-melanomatous skin cancer; carcinoma in situ of breast, oral cavity or cervix) unless disease free for ≥ 2 years
• Subject has used bevacizumab or immune checkpoint blockade to treat GBM
• Lactating or pregnant female
• Positive viral serology for HIV or syphilis at time of screening

2. Study screening

• Subjects having a biopsy only at surgery or tumor cell insufficiency at preparation
• Inability to undergo contrast-enhanced MRI scans
• Subjects receiving investigational study drug for any indication or immunological-based treatment for any reason (Filgrastim may be used for prevention of severe neutropenia)
• Inability to stop or decrease the use of corticosteroid doses to 4 mg/day prior to randomization
• Tumor progression documented according to modified RANO criteria prior to randomization (approximately 5 weeks after surgery)
• Severe, active comorbidity, defined as follow:

1. Subject with clinically defined Acquired Immune-Deficiency Syndrome (AIDS)-defining illness;

2. Subjects with acute hepatitis C or B infection;

3. Severe hepatic impairment (Child-Pugh category C or higher);

4. Electrocardiogram (ECG) with evidence of acute cardiac ischemia prior to randomization;

5. Transmural myocardial infarction or ischemia prior to enrollment;

6. Any other major medical illnesses or psychiatric impairments that in the Investigator's opinion will prevent administration or completion of protocol therapy

• Subject used Gliadel wafer implant in surgery during screening process

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Safe Save Medical Cell Sciences & Technology Co.,Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peng-Wei Hsu, MD

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Locations

Chang Gung Memorial Hospital, Chiayi branch

Chiayi City, , Taiwan

Site Status: RECRUITING

Chang Gung Memorial Hospital, Kaohsiung branch

Kaohsiung City, , Taiwan

Site Status: RECRUITING

Chang Gung Memorial Hospital, Keelung branch

Keelung, , Taiwan

Site Status: RECRUITING

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status: RECRUITING

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status: RECRUITING

Chi Mei Medical Center

Tainan City, , Taiwan

Site Status: RECRUITING

Chang Gung Memorial Hospital, Linkou branch

Taoyuan, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Wen-Kuang Yang, PhD

Role: CONTACT

wkyang@safesavecell.com.tw

+886-3-5506696

Weber Liu, MS

Role: CONTACT

wbliu@safesavecell.com.tw

+886-3-5506696

Facility Contacts

Jen-Tsung Yang, MD/PhD

Role: primary

+886-5-3621000

Jih-Tsun Ho, MD/PhD

Role: primary

+886-7-7317123

Pin-Yuan Chen, MD/PhD

Role: primary

+886-2-24313131

Chiung-Chyi Shen, MD/PhD

Role: primary

+886-5-23592525

E-Jian Lee, MD/PhD

Role: primary

+886-6-2353535

Chin-Hong Chang, MD

Role: primary

+886-6-2812811

Peng-Wei Hsu, MD

Role: primary

+886-3-3281200

References

Chang CN, Huang YC, Yang DM, Kikuta K, Wei KJ, Kubota T, Yang WK. A phase I/II clinical trial investigating the adverse and therapeutic effects of a postoperative autologous dendritic cell tumor vaccine in patients with malignant glioma. J Clin Neurosci. 2011 Aug;18(8):1048-54. doi: 10.1016/j.jocn.2010.11.034. Epub 2011 Jun 28.

Reference Type: RESULT

PMID: 21715171 (View on PubMed)

Woroniecka K, Fecci PE. Immuno-synergy? Neoantigen vaccines and checkpoint blockade in glioblastoma. Neuro Oncol. 2020 Sep 29;22(9):1233-1234. doi: 10.1093/neuonc/noaa170. No abstract available.

Reference Type: DERIVED

PMID: 32691060 (View on PubMed)

Other Identifiers

ADCTA-SSI-G1

Identifier Type: -

Identifier Source: org_study_id