Vaccine for Patients With Newly Diagnosed or Recurrent Low-Grade Glioma

• Sponsor: Jonsson Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01635283
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arm: 1
• Actual Duration (Months): 52.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary purpose of this phase II clinical trial is to determine the safety and effect on survival of patients autologous dendritic cells pulsed with autologous tumor lysate as a treatment for low-grade glioma patients. Other goals of this study are to determine if the vaccine can cause an immune response against patients' cancer cells and slow the growth of their brain tumors

Condition or Disease	Intervention/Treatment	Phase
Adult Diffuse Astrocytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Recurrent Adult Brain Tumor; Adult Oligoastrocytoma	Biological: tumor lysate-pulsed autologous dendritic cell vaccine; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the 5-year progression-free survival (PFS), using intradermal injections of autologous dendritic cells harvested from peripheral blood precursors and pulsed (co-cultured) with tumor lysate derived from surgical tissues in patients with low-grade gliomas.

SECONDARY OBJECTIVES:

1. To monitor overall survival (OS), and cellular immune responses in brain tumor patients injected with tumor lysate-pulsed dendritic cells.

OUTLINE:

Patients receive tumor lysate-pulsed autologous dendritic cell vaccine intradermally (ID) on days 0, 14, and 28.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial Evaluating Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen for the Treatment of Low-grade Glioma
• Actual Study Start Date: Jan 10, 2012
• Actual Primary Completion Date: May 13, 2016
• Actual Study Completion Date: May 13, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (tumor lysate-pulsed autologous dendritic cells) Patients receive autologous glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 0, 14, and 28.	Biological: tumor lysate-pulsed autologous dendritic cell vaccine; Given ID; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) of Low Grade Glioma Patients Treated With Autologous Dendritic Cells Pulsed With Autologous Tumor Lysate [Each case was assessed from the baseline date of surgery to MRI evidence of tumor progression through study completion, up to 44 months.]

   a Kaplan-Meier curve of the PFS of our trial patients was created and compared to the PFS of control patients matched for tumor grade, recurrence number, IDH1 status and 1p/19q status.

Secondary Outcome Measures

1. Overall Survival (OS) [The timeframe for OS was from the date of surgery until the date of death from any cause, up to 44 months.]

   From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months. a Kaplan-Meier curve of the OS of our trial patients was created and compared to the OS of control patients matched for tumor grade, recurrence number, IDH1 status and 1p/19q status.

2. Anti-tumor Immune Responses [Tumor for analysis (CD8, Programmed Death (PD)-1, PD-L1, mutation analysis) was collected at the vaccine-related surgery shortly after enrollment. Blood for analysis (IDH1-specific antibodies) was collected at Day 0, before the first vaccine injection.]

   Tumor and peripheral blood samples were collected from each of the participants and analyzed for the following biomarkers: IDH1-specific antibodies CD8, PD-1, and PD-L1 content, and correlations among those three biomarkers Mutation analysis/sequencing

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with newly diagnosed or recurrent glioma of World Health Organization (WHO) grade II (astrocytoma, oligodendroglioma, and/or oligoastrocytoma) will be eligible for this protocol

• Patients must have had surgical resection at University of California, Los Angeles (UCLA), for which a separate informed consent was signed for the collection of their tumor prior to surgery

• After surgery, a pathological diagnosis of low-grade glioma (WHO grade II) will need to be established

• Patients must be able to read and understand the informed consent document; patients must sign the informed consent indicating that they are aware of the investigational nature of this study.

• Patients must have a Karnofsky performance status (KPS) rating of >= 60 prior to initiating treatment; patients may be enrolled at a KPS of < 60 if it is felt that the patient will have adequate opportunity to recover to a KPS of >= 60 by the initiation of treatment

• Hemoglobin >= 9 gm%

• Absolute granulocyte count >= 1,500

• Platelet count >= 100,000/microliter (uL)

• Serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 times institutional normals

• Bilirubin =< 1.5mg%

• Blood urea nitrogen (BUN) or creatinine =< 1.5 times institutional normals

Exclusion Criteria:

• Subjects with an active infection

• Inability to obtain informed consent because of psychiatric or complicating medical problems

• Unstable or severe intercurrent medical or psychiatric conditions as determined by the Investigator

• Females of child-bearing potential who are pregnant or lactating or who are not using approved contraception

• History of immunodeficiency (e.g., human immunodeficiency virus [HIV]) or autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, vasculitis, polymyositis-dermatomyositis, scleroderma, multiple sclerosis, or juvenile-onset insulin-dependent diabetes) that may be exacerbated by immunotherapy

• Subjects with organ allografts

• Inability or unwillingness to return for required visits and follow-up exams

• Subjects who have an uncontrolled systemic malignancy that is not in remission

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095

Sponsors and Collaborators

• Jonsson Comprehensive Cancer Center

Investigators

• Principal Investigator: Robert Prins, Jonsson Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonsson Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT01635283
• Other Study ID Numbers: 11-002665; NCI-2012-00980
• First Posted: Jul 9, 2012
• Last Update Posted: Nov 4, 2020
• Last Verified: May 1, 2016

• Additional relevant MeSH terms: Glioma; Astrocytoma; Oligodendroglioma

Study Results

Participant Flow

Recruitment Details	Dates of recruitment period: 1/2012 - 8/2015 Types of location: Medical clinic
Pre-assignment Detail	Study enrollment patients must satisfy inclusion criteria, screening evaluations (vital signs, history, physical, neurological exams, Karnofsky Performance Scale, brain MRI , urinalysis, complete blood count, differential, platelets, coagulation tests), underwent leukapheresis, and had suitable Dendritic Cell (DC) Vaccine manufactured for them.

Arm/Group Title	Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells)
Arm/Group Description	Patients receive autologous glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 0, 14, and 28. tumor lysate-pulsed autologous dendritic cell vaccine: Given ID laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	5
COMPLETED	1
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells)
Arm/Group Description	Patients receive autologous glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 0, 14, and 28. tumor lysate-pulsed autologous dendritic cell vaccine: Given ID laboratory biomarker analysis: Correlative studies
Overall Participants	5
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.2 (21.95)
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) of Low Grade Glioma Patients Treated With Autologous Dendritic Cells Pulsed With Autologous Tumor Lysate
Description	a Kaplan-Meier curve of the PFS of our trial patients was created and compared to the PFS of control patients matched for tumor grade, recurrence number, IDH1 status and 1p/19q status.
Time Frame	Each case was assessed from the baseline date of surgery to MRI evidence of tumor progression through study completion, up to 44 months.

Outcome Measure Data

Analysis Population Description

Completed the maximum time allowed on study without being affected by Tumor Recurrence or Progression.

Arm/Group Title	Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells)
Arm/Group Description	Patients receive autologous glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 0, 14, and 28. tumor lysate-pulsed autologous dendritic cell vaccine: Given ID laboratory biomarker analysis: Correlative studies
Measure Participants	5
0-6 months	0 0%
7-12 months	1 20%
13-18 months	1 20%
19-24 months	1 20%
25-30 months	0 0%
>30 months	2 40%

2. Secondary Outcome

Title	Overall Survival (OS)
Description	From date of enrollment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months. a Kaplan-Meier curve of the OS of our trial patients was created and compared to the OS of control patients matched for tumor grade, recurrence number, IDH1 status and 1p/19q status.
Time Frame	The timeframe for OS was from the date of surgery until the date of death from any cause, up to 44 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells)
Arm/Group Description	Patients receive autologous glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 0, 14, and 28. tumor lysate-pulsed autologous dendritic cell vaccine: Given ID laboratory biomarker analysis: Correlative studies
Measure Participants	5
Deceased	0 0%
Alive	5 100%
Lost to Follow-Up	0 0%
Withdrawal by Subject	0 0%

3. Secondary Outcome

Title	Anti-tumor Immune Responses
Description	Tumor and peripheral blood samples were collected from each of the participants and analyzed for the following biomarkers: IDH1-specific antibodies CD8, PD-1, and PD-L1 content, and correlations among those three biomarkers Mutation analysis/sequencing
Time Frame	Tumor for analysis (CD8, Programmed Death (PD)-1, PD-L1, mutation analysis) was collected at the vaccine-related surgery shortly after enrollment. Blood for analysis (IDH1-specific antibodies) was collected at Day 0, before the first vaccine injection.

Outcome Measure Data

Analysis Population Description

Quantitative multiplex immuno-histochemical (IHC) of pre-treatment glioma microenvironment of IDH1-specific antibodies

Arm/Group Title	%CD8+/Field	%PD-1+/Field	%PD-L1+/Field
Arm/Group Description
Measure Participants	5	5	5
Mean (Standard Deviation) [percentage of cells per field]	1.26 (1.03)	1.35 (1.04)	6.76 (3.30)

Adverse Events

Time Frame	The timeframe for adverse event reporting was from the day of the first vaccine treatment until the patient discontinued the study for any reason, up to 44 months.
Arm/Group Title	Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells)
Arm/Group Description	Patients receive autologous glioma tumor lysate-pulsed autologous dendritic cell vaccine ID on days 0, 14, and 28. tumor lysate-pulsed autologous dendritic cell vaccine: Given ID laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells)
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Serious Adverse Events
	Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells)
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Tumor Lysate-pulsed Autologous Dendritic Cells)
	Affected / at Risk (%)	# Events
Total	3/5 (60%)
Blood and lymphatic system disorders
Anemia	1/5 (20%)	1
Gastrointestinal disorders
Nausea	1/5 (20%)	1
General disorders
Headache	2/5 (40%)	2
Fatigue	2/5 (40%)	2
Rhinorrhea	1/5 (20%)	1
Infections and infestations
Urinary Tract Infection	1/5 (20%)	1
Upper respritory infection	1/5 (20%)	1
Musculoskeletal and connective tissue disorders
Fractures	1/5 (20%)	1
Myalgia	1/5 (20%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinomas	1/5 (20%)	1
Nervous system disorders
Seizure	2/5 (40%)	2
Dysphasia	1/5 (20%)	1
Visual Distortions	1/5 (20%)	1
cognitive slowness	1/5 (20%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.