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Glioblastoma MultiformePhase 2NCT02772094

Dendritic Cell-Based Tumor Vaccine Adjuvant Immunotherapy of Human Glioblastoma Multiforme (WHO Grade IV Gliomas)

A Phase 2 study testing Single arm, open-label in people with Glioblastoma Multiforme and Glioblastoma, run by China Medical University Hospital at 1 site in Taiwan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Purposes: The purpose of this phase-II clinical trial is to determine whether or not ADCTA-G, a biologic "vaccine" preparation of patient's own dendritic cell (DC) for glioblastoma multiforme (GBM) treatment, is safe and effective in extending the GBM patient's life. Read more about this study

Who is it for?
Ages 13 to 70 years
Conditions the study is for
Glioblastoma Multiforme, Glioblastoma
What is being tested?
Single arm, open-label
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteTaiwan
Study dates
May 2005to Dec 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 to 70 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Histopathologically proved WHO grade-4 malignant glioma
  • Age: 13 years (physically mature) to 70 years
  • Karnofsky performance score before surgery: ≧70 [Karnofsky 1951] .
  • Adequate liver functions, including serum alanine aminotransferase (ALT or SGPT), serum aspartate aminotransferase (AST or SGOT), and alkaline phosphatase at ≤3.0 times upper limits of normal levels (ULN), total bilirubin ≤1.5mg/dl), total serum bilirubin <3 mg/dl
  • Adequate renal function (BUN ≤25 mg/ml; creatinine≤1.8 mg/dl,creatinine clearance >50 ml/min prior to starting therapy
  • Hemoblobin≧8 g/dl,platelet ≧100,000/μl,WBC>2,000/μl; absolute neutrophil count >1,000/μl
  • Prothrombin time and partial thromboplastin time≦1.5x the normal upper limit

Who cannot join

  • Pregnant or breast feeding
  • With radioactive implant
  • Acute infection, fever
  • Active collagen diseases
  • Acute cardiovascular diseases
  • Acute viral hepatitis
Show all 10Show fewer
  • Syphilis
  • Human immunodeficiency virus (HIV) infection
  • Carrier of other transmissible infection
  • Immune deficiency due to chronic disease

Trial locations and contacts

1 site in 1 country.

Taiwan1 site
  • China Medical University Hospital

    Taichung, 404

Other trials in Taiwan

About this study

Official title: Autologous Dendritic Cell-Based Adjuvant Immunotherapy of Malignant Gliomas (WHO Grade IV Glioblastoma Multiforme) - Phase II Clinical Trial

Purposes:

The purpose of this phase-II clinical trial is to determine whether or not ADCTA-G, a biologic "vaccine" preparation of patient's own dendritic cell (DC) for glioblastoma multiforme (GBM) treatment, is safe and effective in extending the GBM patient's life. The current conventional multi-modal regimen that may include surgery for tumor resection or biopsy, temozolomide (TMZ) combined chemo-radiotherapy (CCRT) and TMZ adjuvant chemotherapy almost always leaves residual GBM cells to cause fatal recurrence, leading to medium survival period of 8 -15 months and over-all survival rates of about 30% in 2 years and <3% in 5 years after diagnosis/surgery. Thus, in neurosurgical oncology practice, GBM patients in the first 2-year period during and after receiving multi-modal therapy are watched closely for possible GBM tumor recurrence and mortal disease relapse and immediately given palliative treatments and health care, until death. In this phase-II trial, GBM patient participants who receive ADCTA-G "vaccine" adjuvant immunotherapy (added to the conventional multi-modal regimen) will be similarly watched closely by treatments and health care visits at least biweekly from the date of surgery/diagnosis to 24 months, and if alive followed by weekly phone calls and scheduled health care visits at least once every 3 months, up to 72 months after surgery. In the trial protocol, ADCT-G in 10 doses is administered after surgery, over a period of 6 or 8 months, as an adjuvant immunotherapy of the conventional multimodal regimen. Individual ADCTA-G "vaccine" lot of every participant GBM patient is manufactured from patient's own monocyte-derived dendritic cells and the patient's own tumor cell antigens, both of which are prepared by a distinct method of procedures performed within air particle-free barrier good laboratory practice (GLP) facility. Previous phase I/II clinical trial of ADCTA-G "vaccine" immunotherapy administered as an adjuvant to the conventional multimodal regimen, has obtained promising safety and efficacy results for GBM patients in a clinical center. This phase-II clinical trial in China Medical University Hospital-Taichung will employ essentially the same clinical protocols and the same distinct "vaccine" manufacturing method of standard operational procedures (SOP), that is, the conventional multimodal regimen plus adjuvant immunotherapy using personal ADCTA-G "vaccine" lot for every GBM patient participants.

Read the detailed description

Rationale and Background :

Glioblastoma multiforme (GBM) and other WHO grade IV malignant gliomas of the brain are among the most lethal of human cancers. Despite current intensive multimodal regimen including the use of temozolomide (TMZ) for combined chemo-radiotherapy (CCRT) and for subsequent adjuvant chemotherapy, the medium survival period of GBM patients is still 8-16 months after diagnosis and surgery, with prognosis varied according to demographic features such as age, radiotherapy types and chemotherapy measures.These fatal brain cancers in general contain cancer cells with mutation in certain genes. Also, the mutated GBM cancer cells are usually heterogenous; and different GBM patients may have individual sets of heterogenous glioma cancer cells in which the mutant genes would generate altered antigens that can be recognized by the patient's adaptive immune system to mount immuno-targeting responses to reject or kill the GBM tumor cells. However, GBM is still fatal because it is highly immunosuppressive, i.e. able to anergize the immune effector cells in the body. Although surgical resection of rapidly expanding tumor bulk will prevent further physical damages to the brain and curtail the immunosuppression, the already anergized effector T lymphocytes still require functional restoration. On the other hand, post-surgical TMZ CCRT and adjuvant chemotherapy may weaken the residual tumor cells, but TMZ will also impair if not kill the active T lymphocytes in general, including anti-GBM lymphocytes. It is therefore important to exploit the adaptive immunity system for effective therapy of GBM. To apply the adaptive immunotherapy, it is best to use each patient's surgical tumor specimen to prepare the own individual "tumor regression antigens" for loading onto the patient's own dendritic cells (the "professional" antigen processing and presenting cells of the immune system). Dendritic cells loaded with tumor-specific antigens, upon maturation and inoculation ("vaccination"), would migrate/home to the T cell area of lymph nodes and stimulate proliferation of tumor-specific cytotoxic T lymphocyte that would move out of lymph node to find the brain tumor lesion to attack and eradicate the residual GBM tumor cells, resulting in prevention of GBM recurrence.

With fore-mentioned working hypotheses, the investigators carried out translational research from 1997 to 2002. A special method has been developed for production of an immunotherapeutic, which is named "autologous dendritic cell/autologous tumor cell antigens of GBM" (ADCTA-G). For clinical trial purpose, the investigators have established standard operational procedures (SOP) of the method with the use of clinical Good Manufacturing Practice (cGMP)-grade cytokines and pharmaceutical reagents. Individual ADCTA-G lots of all participant GBM patients are manufactured in high efficiency particle arresting (HEPA) air-filtered, germ-free bio-safety barrier clinical Good Laboratory Practice (cGLP) facilities. The phase I/II clinical trial was officially approved by Taiwan Department of Health and performed in a clinical center to demonstrate that ADCTA-G adjuvant immunotherapy was safe and apparently could prolong the survival for GBM patients.

Being tested
Single arm, open-label
Keywords
glioblastoma multiforme, glioblastoma, newly diagnosed glioblastoma, immunotherapy, dendritic cells, grade IV astrocytoma, oncology, neurology, glioma, brain tumor, ADCTA-G
Medical subject headings
Glioblastoma, Neoplasms, Glioma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Single arm, open-labelBiological

    Also called ADCTA-G

    Biological: ADCTA-G. Biological: autologous DC loaded with irradiated autologous tumor cells. Biological: dendritic cell "vaccine". Drug: 180mg/m2•per day temozolomide prior and concomitant with radiotherapy. Radiotherapy: Local ionizing radiation 200 centigray(cGy)/day, 5 successive days per week for 6 weeks, total dose of 6000 cGy.

    Drug: Adjuvant chemotherapy-temozolomide (TMZ) monthly cycle, 200mg/m2•per day continued for 5 days in the beginning of every month, 6 cycles of TMZ.

Study groups in NCT02772094
Study groupRoleWhat they receive
Single arm, open-labelExperimentalExperimental: ADCTA-G total 10 doses, each dose (30+/-5 millions autologous dendritic cells plus 6+/-0.5 millions 100Gy-irradiated short-term cultured autologous GBM tumor cells) divided in 2 halves for subcutaneous injection into both axillar areas, in a course of 6 months (sequential series of weekly injections 4 times, bi-weekly injections twice; then monthly injections 4 times. Experimental: ADCTA-G total 10 doses, each dose (similar fore-mentioned numbers of 5:1 ratio of autologous dendritic cells and irradiated short-term cultured autologous GBM tumor cells) divided into 2 injections administered subcutaneously in both axillar areas, in a course of 8 months (sequential series of bi-weekly injections 4 times, then monthly injections 6 times).
Receives: Biological: Single arm, open-label

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival with measures of medium survival period (in days) and annual survival rates (in %)

    The primary end-point is overall survival (OS), days measured from post-recruitment surgery date (tumor resection or biopsy) to date of death due to GBM or other causes, and if alive, to date of weekly phone calls and health care visit every 3 months, up to 6 years. Survival days of patients are depicted on Kaplan-Meier plots to show the medium survival period (days when 50% patients remained alive) and annual rates (% living patients per total) every year up to 5 years, and by log rank test to find statistical probability p value.

    Study groups of ADCTA-G immunotherapy plus conventional multimodal regimen will be compared to reference groups treated with conventional multimodal regimen (no ADCTA or other immunotherapy).

    Measured: Post-recruitment surgery to death due to GBM or any other causes; close follow-up at leas by biweekly health care or emergency visits for 24 months, then weekly phone calls and scheduled visits at least every 3 months, up to 6 years after surgery

  2. Adverse effects, acute and chronic, assessed according to NCI CTCAE Version 3

    Acute or delayed/chronic adverse effects, graded according to NCI CTCAE Version 3.0, e.g. temozolomide combined chemo-radiotherapy(CCRT)-/GBM-caused lymphopenia, measured by lymphocytes/microL blood, and by % of patients with lymphopenia of grade 1, 2, 3, or 4 severity.

    Measured: Post-recruitment surgery to death, due to ADCTA-G, GBM disease or temozolomide chemotherapy; if alive, bi-weekly follow up for 24 months after surgery and then at least one visit in 3 months, up to 72 months

Secondary outcomes (1)
  1. Disease progression-free period

    Progression-free survival period (days) is from date of surgery (tumor resection or biopsy) to date of neurological symptoms/signs relapse, verified by brain magnetic resonance (MRI) imaging, which is performed before and after surgery, and when symptoms and signs of disease progression occur, and subsequently one MRI scan in 3 months, till death or up to 6 years. The progression-free survival days of patient groups are depicted as Kaplan-Meier plots to show medium progression-free period (days when 50% patients remain free from GBM relapse) and annual rates (% progression-free patients of the total) from 1 to 5 years. Study groups of ADCTA-G immunotherapy plus conventional multimodal regimen will be compared to GBM reference groups with conventional therapy without immunotherapy.

    Measured: From recruitment surgery to death, or if alive, biweekly for 24 months, and then weekly phone calls and at least once in 3 months, up to 72 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2016 (estimated)
  2. Study startMay 2005
  3. Primary completionDec 2014
  4. Study completionDec 2016 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02772094
Sponsor's protocol ID
DMR94-IRB-043-1
Status last verified
May 2016
First submitted
3 Feb 2016
Last updated
13 May 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes

Publications

  • 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.

    PubMed 21715171

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Single arm, open-label in people with Glioblastoma Multiforme and Glioblastoma, run by China Medical University Hospital at 1 site in Taiwan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 13 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival with measures of medium survival period (in days) and annual survival rates (in %) (time frame: Post-recruitment surgery to death due to GBM or any other causes; close follow-up at leas by biweekly health care or emergency visits for 24 months, then weekly phone calls and scheduled visits at least every 3 months, up to 6 years after surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02772094, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2016.

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