Study of DC Vaccination Against Glioblastoma

NCT01567202 | Unknown Phase 2 DMC

• 1 other identifier: DC81001115
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II study in a single center to determine the efficacy of autologous dendritic cells (DCs) loaded with autogeneic glioma stem-like cells (A2B5+) administered as a vaccination in adults with glioblastoma multiforme (primary or secondary).

Conditions

Glioma; Glioblastoma Multiforme; Neoplasms

Keywords

Brain tumor; Glioma; Glioblastoma; Tumor stem cells; Immunotherapy; Vaccine

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) of the treatment using DC Vaccination for Glioblastoma with molecular markers for immunotherapy.

  The objective response rate (ORR) is defined as the proportion of patients who achieve radiographic partial or complete response (PR or CR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guideline.Molecular markers are based on the mutation (MT) status of isocitrate dehydrogenase (IDH1/2) and telomerase reverse transcriptase (TERT).

  Every 4 weeks from baseline to 6 months.

Secondary Outcomes (2)

• Progression free survival

  Every 4 weeks from baseline to 6 months.

• Overall survival

  within 2 years after the surgery

Study Arms (2)

Arm DC

EXPERIMENTAL

In this arm, the patients will receive DC vaccination in addition to the standard therapy, including Surgery, Chemotherapy, and Radiotherapy.

Procedure: Surgery; Drug: Chemotherapy; Radiation: Radiotherapy; Biological: DC vaccination

Arm Placebo

PLACEBO COMPARATOR

In this arm, the patients will receive blank placebo instead of the DC vaccination in addition to the standard therapy.

Procedure: Surgery; Drug: Chemotherapy; Radiation: Radiotherapy; Drug: blank placebo

Interventions

Surgery PROCEDURE

Maximum resection of the tumor (≥95%) with the help of conventional or intraoperative MRI neuronavigation. Confirmation will be proceeded by the contrast MRI within 72 hours after surgery.

Arm DC; Arm Placebo

Chemotherapy DRUG

Temozolomide(TMZ), 200mg·m\^-2·d ×5 days，28 days every cycle. 6 cycles of TMZ are recommended.

Arm DC; Arm Placebo

Radiotherapy RADIATION

Standard dose, 4500 cGy to tumor with 3-cm margins, 1500 cGy boost to tumor bed.

Arm DC; Arm Placebo

DC vaccination BIOLOGICAL

Eight to ten million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.

Arm DC

blank placebo DRUG

Saline that has the same appearance with DC vaccine.

Arm Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed brain glioblastoma multiforme and molecular subgroups of IDH1 wildtype TERT mutation。
• Patients with maximum safe resection of the tumor (≥95%) confirmed with contrast MR within 72 hours after surgery.
• Age from 18 through 70 years.
• Karnofsky performance score of ≥ 60%.
• Adequate organ function within 14 days of study registration including the following:
• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count, (ANC) ≥ 1.0×10\^9/L, platelets ≥100×10\^9/L; hemoglobin ≥ 9 g/dL. Hepatic: bilirubin ≤1.3 mg/dL or 0-22 mmol/L, aspartate transaminase (AST) and alanine transaminase (ALT) \< 3×upper limit of normal (ULN). Renal: Normal serum Creatinine for age (below) or creatinine clearance \>60 ml/min/1.73 m\^2. Electrocardiogram: normal.
• Written informed consent must be obtained from all patients, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

You may not qualify if:

• Pregnant or breast-feeding patients. Pregnancy testing will be performed on all menstruating females within 14 days of study enrollment.
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with history of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immuno-suppression), or medication of cortisol.
• Patients with any conditions that could potentially alter immune function (e.g., AIDS, multiple sclerosis, diabetes, renal failure).
• Patients currently received any other investigational agents.

Sponsors & Collaborators

• Huashan Hospital: lead
• Fudan University: collaborator

Study Sites (1)

Huashan hospital, Fudan university

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

Related Publications (4)

• Hua W, Yao Y, Chu Y, Zhong P, Sheng X, Xiao B, Wu J, Yang B, Mao Y, Zhou L. The CD133+ tumor stem-like cell-associated antigen may elicit highly intense immune responses against human malignant glioma. J Neurooncol. 2011 Nov;105(2):149-57. doi: 10.1007/s11060-011-0572-y. Epub 2011 Apr 11.

  PMID: 21479962 BACKGROUND

• Hua Wei, Yao Yu, Chu Yiwei, Zhong Ping, Zhang Rong, Zhu Wei, Wu Jingsong, Ma Dexuan, Xu Ming, Mao Ying, Zhou Liangfu. Phase I study of dendritic cells pulsed with tumor stem-like cells associated antigens against malignant glioma in recurrent patients. Chinese Journal of Neurosurgery (Chinese). 2011, 27(1): 90-94.

  BACKGROUND

• Xu M, Yao Y, Hua W, Wu Z, Zhong P, Mao Y, Zhou L, Luo F, Chu Y. Mouse glioma immunotherapy mediated by A2B5+ GL261 cell lysate-pulsed dendritic cells. J Neurooncol. 2014 Feb;116(3):497-504. doi: 10.1007/s11060-013-1334-9. Epub 2014 Jan 8.

  PMID: 24398615 BACKGROUND

• Yao Y, Luo F, Tang C, Chen D, Qin Z, Hua W, Xu M, Zhong P, Yu S, Chen D, Ding X, Zhang Y, Zheng X, Yang J, Qian J, Deng Y, Hoon DSB, Hu J, Chu Y, Zhou L. Molecular subgroups and B7-H4 expression levels predict responses to dendritic cell vaccines in glioblastoma: an exploratory randomized phase II clinical trial. Cancer Immunol Immunother. 2018 Nov;67(11):1777-1788. doi: 10.1007/s00262-018-2232-y. Epub 2018 Aug 22.

  PMID: 30159779 BACKGROUND

MeSH Terms

Conditions

Glioma; Glioblastoma; Neoplasms; Brain Neoplasms

Interventions

Surgical Procedures, Operative; Drug Therapy; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Liangfu Zhou, M.D.

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liangfu Zhou, M.D.

CONTACT

86-21-52889999-7206; lfzhouc@126.com

Wei Hua, M.D., Ph.D.

CONTACT

15800589540; doctor.huawei@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Ph.D.

Study Record Dates

• First Submitted: March 26, 2012
• First Posted: March 30, 2012
• Study Start: March 1, 2012
• Primary Completion: November 1, 2020
• Study Completion: February 1, 2021
• Last Updated: September 9, 2020

Record last verified: 2020-09

Locations

CN (1)