A Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma

NCT ID: NCT01498328

Last Updated: 2020-02-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-31

Study Completion Date

2016-05-17

Brief Summary

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The purpose of this research study is to find out whether adding an experimental vaccine called rindopepimut (also known as CDX-110) to the commonly used drug bevacizumab can improve progression free survival (slowing the growth of tumors) of patients with relapsed EGFRvIII positive glioblastoma.

Detailed Description

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This Phase II study will enroll patients into three groups. Group 1 are patients who have never been treated with bevacizumab. These patients will be randomly assigned to receive either rindopepimut/GM-CSF or KLH, each along with bevacizumab. Treatment assignment for Group 1 will be blinded. Group 2 and Group 2C patients are those who are refractory to bevacizumab (experienced recurrence or progression of glioblastoma while on bevacizumab or within 2 months of discontinuing bevacizumab). These patients will all receive rindopepimut/GM-CSF along with bevacizumab. Patients will be treated until disease progression or intolerance and all patients will be followed for survival. Patients may be treated with other therapies that are not part of the study after discontinuing treatment with the study vaccine.

Conditions

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Glioblastoma Small Cell Glioblastoma Giant Cell Glioblastoma Gliosarcoma Glioblastoma With Oligodendroglial Component Recurrent Glioblastoma Relapsed Glioblastoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Group 1a: Bevacizumab Naïve with Bevacizumab + rindopepimut.

About half of the patients who have never received treatment with bevacizumab will receive rindopepimut/GM-CSF in a blinded fashion in combination with bevacizumab.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

A vascular endothelial growth factor (VEGF)-specific humanized monoclonal antibody angiogenesis inhibitor. Infusions of 10 mg/kg of bevacizumab will begin on day 1 and will be administered every two weeks until progression of disease or intolerance during the treatment period.

Rindopepimut (CDX-110) with GM-CSF

Intervention Type DRUG

Rindopepimut/GM-CSF will initially be given three times, two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM-CSF.

Group 1b: Bevacizumab Naïve with Bevacizumab + KLH control

About half of the patients who have never received treatment with bevacizumab will receive KLH in a blinded fashion in combination with bevacizumab.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

A vascular endothelial growth factor (VEGF)-specific humanized monoclonal antibody angiogenesis inhibitor. Infusions of 10 mg/kg of bevacizumab will begin on day 1 and will be administered every two weeks until progression of disease or intolerance during the treatment period.

KLH

Intervention Type DRUG

KLH will initially be given three times, two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 100 mcg of KLH.

Group 2 and 2C: Refractory to Bevacizumab

Patients with progressive disease while currently on or within two months after discontinuing bevacizumab will be administered rindopepimut/GM-CSF while continuing (or restarting if they had stopped bevacizumab).

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

A vascular endothelial growth factor (VEGF)-specific humanized monoclonal antibody angiogenesis inhibitor. Infusions of 10 mg/kg of bevacizumab will begin on day 1 and will be administered every two weeks until progression of disease or intolerance during the treatment period.

Rindopepimut (CDX-110) with GM-CSF

Intervention Type DRUG

Rindopepimut/GM-CSF will initially be given three times, two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM-CSF.

Interventions

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Bevacizumab

A vascular endothelial growth factor (VEGF)-specific humanized monoclonal antibody angiogenesis inhibitor. Infusions of 10 mg/kg of bevacizumab will begin on day 1 and will be administered every two weeks until progression of disease or intolerance during the treatment period.

Intervention Type DRUG

Rindopepimut (CDX-110) with GM-CSF

Rindopepimut/GM-CSF will initially be given three times, two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM-CSF.

Intervention Type DRUG

KLH

KLH will initially be given three times, two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 100 mcg of KLH.

Intervention Type DRUG

Other Intervention Names

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Avastin

Eligibility Criteria

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Inclusion Criteria

Among other criteria, patients must meet the following conditions to be eligible for the study:

1. Age ≥18 years of age.
2. Histologic diagnosis of glioblastoma (WHO Grade IV).
3. Documented EGFRvlll positive tumor status (central lab confirmation).
4. First or second relapse of de novo glioblastoma or first diagnosis or first relapse of secondary glioblastoma.
5. Previous treatment must include surgery, conventional radiation therapy and temozolomide (TMZ).
6. Screening MRI must be obtained at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy.
7. KPS of ≥ 70%.
8. If applicable, systemic corticosteroid therapy must be at a dose of ≤ 4 mg of dexamethasone or equivalent per day during the week prior to Day 1.
9. Evaluable disease in Groups 1 and 2; measurable disease in Group 2C
10. Life expectancy \> 12 weeks.
11. Patients in Group 2 and 2C must have had disease progression while receiving bevacizumab or within 2 months of treatment with bevacizumab.

Exclusion Criteria

Among other criteria, patients who meet the following conditions are NOT eligible for the study:

1. Subjects unable to undergo an MRI with contrast.
2. History, presence, or suspicion of metastatic disease
3. Prior receipt of vaccination against EGFRvIII.
4. Any known contraindications to receipt of study drugs, including known allergy or hypersensitivity to keyhole limpet hemocyanin (KLH), GM-CSF (sargramostim; LEUKINE®), polysorbate 80 or yeast derived products, or a history of anaphylactic reactions to shellfish proteins.
5. Use of non-protein based investigational therapy within 14 days prior to Day 1 or use of antibody-based investigational therapy within 28 days prior to Day 1.
6. Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
7. Evidence of recent hemorrhage on screening MRI of the brain
8. Evidence of current drug or alcohol abuse.
9. Patients in Group 1 must not have received prior treatment with bevacizumab.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celldex Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

St. Joseph's Hospital and Medical Center / Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Site Status

University of Southern California (USC) Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UC Irvine Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Stanford Cancer Institute, Stanford University

Stanford, California, United States

Site Status

University of Colorado, Denver

Aurora, Colorado, United States

Site Status

Memorial Cancer Institute

Hollywood, Florida, United States

Site Status

Orlando Health, Inc.

Orlando, Florida, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Site Status

Atlanta Cancer Care

Atlanta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

NorthShore University Health System

Evanston, Illinois, United States

Site Status

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute and Mass General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Sparrow Cancer Center

Lansing, Michigan, United States

Site Status

John Nasseff Neuroscience Institute, Abbott Northwestern Hospital, 800 e. 28th Str. MR

Minneapolis, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

New Jersey Neuroscience Institute JFK Medical Center

Edison, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Dent Neurologic Institute, 3980 Sheridan Dr, 3rd Flr Clinical Rsch

Amherst, New York, United States

Site Status

The Long Island Brain Tumor Center at Neurology Surgery, P.C.

Commack, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Stony Brook University Hospital

Stony Brook, New York, United States

Site Status

The Preston Robert Tisch Brain Tumor Center; Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Site Status

University of Cincinnati Cancer Institute

Cincinnati, Ohio, United States

Site Status

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Legacy Research Institute

Portland, Oregon, United States

Site Status

Lehigh Valley Hospital-John and Dorothy Morgan Cancer Center

Allentown, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Texas Oncology Midtown

Austin, Texas, United States

Site Status

Baylor Research Institute

Dallas, Texas, United States

Site Status

UT Health Science Center, Houston Memorial Hermann Hospital, 6400 Fannin Street, #2800

Houston, Texas, United States

Site Status

Utah Cancer Specialists

Salt Lake City, Utah, United States

Site Status

Swedish Neuroscience Research

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Reardon DA, Desjardins A, Vredenburgh JJ, O'Rourke DM, Tran DD, Fink KL, Nabors LB, Li G, Bota DA, Lukas RV, Ashby LS, Duic JP, Mrugala MM, Cruickshank S, Vitale L, He Y, Green JA, Yellin MJ, Turner CD, Keler T, Davis TA, Sampson JH; ReACT trial investigators. Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial. Clin Cancer Res. 2020 Apr 1;26(7):1586-1594. doi: 10.1158/1078-0432.CCR-18-1140. Epub 2020 Feb 7.

Reference Type RESULT
PMID: 32034072 (View on PubMed)

Gatson NT, Weathers SP, de Groot JF. ReACT Phase II trial: a critical evaluation of the use of rindopepimut plus bevacizumab to treat EGFRvIII-positive recurrent glioblastoma. CNS Oncol. 2016;5(1):11-26. doi: 10.2217/cns.15.38. Epub 2015 Dec 15.

Reference Type DERIVED
PMID: 26670466 (View on PubMed)

Other Identifiers

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CDX110-06

Identifier Type: -

Identifier Source: org_study_id

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