Back to resultsA Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma (ReACT)
Primary Purpose
Glioblastoma, Small Cell Glioblastoma, Giant Cell Glioblastoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab
Rindopepimut (CDX-110) with GM-CSF
KLH
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma focused on measuring EGFRvIII, Glioblastoma, Rindopepimut, CDX-110, Small cell, Giant cell, Brain Cancer, Brain Tumor, Gliosarcoma, oligodendroglial, radiotherapy, chemoradiation, Tumor, Bevacizumab, Relapsed, Returned, Recurrent, EGFR variant III
Eligibility Criteria
Inclusion Criteria:
Among other criteria, patients must meet the following conditions to be eligible for the study:
- Age ≥18 years of age.
- Histologic diagnosis of glioblastoma (WHO Grade IV).
- Documented EGFRvlll positive tumor status (central lab confirmation).
- First or second relapse of de novo glioblastoma or first diagnosis or first relapse of secondary glioblastoma.
- Previous treatment must include surgery, conventional radiation therapy and temozolomide (TMZ).
- Screening MRI must be obtained at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy.
- KPS of ≥ 70%.
- 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.
- Evaluable disease in Groups 1 and 2; measurable disease in Group 2C
- Life expectancy > 12 weeks.
- 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:
- Subjects unable to undergo an MRI with contrast.
- History, presence, or suspicion of metastatic disease
- Prior receipt of vaccination against EGFRvIII.
- 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.
- 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.
- Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
- Evidence of recent hemorrhage on screening MRI of the brain
- Evidence of current drug or alcohol abuse.
- Patients in Group 1 must not have received prior treatment with bevacizumab.
Sites / Locations
- University of Alabama at Birmingham
- St. Joseph's Hospital and Medical Center / Barrow Neurological Institute
- Kaiser Permanente Los Angeles Medical Center
- University of Southern California (USC) Norris Comprehensive Cancer Center
- UC Irvine Chao Family Comprehensive Cancer Center
- University of California San Francisco
- Stanford Cancer Institute, Stanford University
- University of Colorado, Denver
- Memorial Cancer Institute
- Orlando Health, Inc.
- Tampa General Hospital
- Piedmont Atlanta Hospital
- Atlanta Cancer Care
- Rush University Medical Center
- University of Chicago
- NorthShore University Health System
- The Johns Hopkins Hospital
- Dana-Farber Cancer Institute and Mass General Hospital
- University of Michigan Comprehensive Cancer Center
- Sparrow Cancer Center
- John Nasseff Neuroscience Institute, Abbott Northwestern Hospital, 800 e. 28th Str. MR
- Washington University School of Medicine
- New Jersey Neuroscience Institute JFK Medical Center
- Hackensack University Medical Center
- Dent Neurologic Institute, 3980 Sheridan Dr, 3rd Flr Clinical Rsch
- The Long Island Brain Tumor Center at Neurology Surgery, P.C.
- University of Rochester Medical Center
- Stony Brook University Hospital
- The Preston Robert Tisch Brain Tumor Center; Duke University Medical Center
- Wake Forest Baptist Health
- University of Cincinnati Cancer Institute
- Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
- Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
- Legacy Research Institute
- Lehigh Valley Hospital-John and Dorothy Morgan Cancer Center
- University of Pennsylvania
- University of Pittsburgh Cancer Institute
- Rhode Island Hospital
- Vanderbilt-Ingram Cancer Center
- Texas Oncology Midtown
- Baylor Research Institute
- UT Health Science Center, Houston Memorial Hermann Hospital, 6400 Fannin Street, #2800
- Utah Cancer Specialists
- Swedish Neuroscience Research
- University of Washington Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Group 1a: Bevacizumab Naïve with Bevacizumab + rindopepimut.
Group 1b: Bevacizumab Naïve with Bevacizumab + KLH control
Group 2 and 2C: Refractory to Bevacizumab
Arm Description
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.
About half of the patients who have never received treatment with bevacizumab will receive KLH in a blinded fashion in combination with 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).
Outcomes
Primary Outcome Measures
Groups 1 and 2: Progression-free survival rate
Evaluate the antitumor activity of rindopepimut in adult patients with relapsed glioblastoma, as measured by the progression-free survival rate at 6 months post-Day 1 (PFS 6).
Group 2C: Objective Response Rate
Evaluate the anti-tumor activity of rindopepimut in adult patients with relapsed glioblastoma, as measured by the objective response rate (ORR) for patients with measurable disease at study entry.
Secondary Outcome Measures
Safety and Tolerability
Safety and tolerability will be evaluated by comparing the treatment regimens in regards to vital sign measurements, physical and neurological examinations, adverse events reporting, and Karnofsky performance status
Anti-tumor activity
Evaluated by comparing the treatment regimens for anti-tumor activity, including objective response rate, overall progression free survival (PFS), and overall survival (OS) for Groups 1 and 2; and PFS6, overall PFS, and OS for Group 2C.
EGFRvIII-specific immune response
Characterize the EGFRvIII specific immune response to rindopepimut.
Full Information
NCT ID
NCT01498328
First Posted
December 21, 2011
Last Updated
February 12, 2020
Sponsor
Celldex Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT01498328
Brief Title
A Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma
Acronym
ReACT
Official Title
A Phase II Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
December 2011 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
May 17, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celldex Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Small Cell Glioblastoma, Giant Cell Glioblastoma, Gliosarcoma, Glioblastoma With Oligodendroglial Component, Recurrent Glioblastoma, Relapsed Glioblastoma
Keywords
EGFRvIII, Glioblastoma, Rindopepimut, CDX-110, Small cell, Giant cell, Brain Cancer, Brain Tumor, Gliosarcoma, oligodendroglial, radiotherapy, chemoradiation, Tumor, Bevacizumab, Relapsed, Returned, Recurrent, EGFR variant III
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
127 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1a: Bevacizumab Naïve with Bevacizumab + rindopepimut.
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 1b: Bevacizumab Naïve with Bevacizumab + KLH control
Arm Type
Experimental
Arm Description
About half of the patients who have never received treatment with bevacizumab will receive KLH in a blinded fashion in combination with bevacizumab.
Arm Title
Group 2 and 2C: Refractory to Bevacizumab
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
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
Intervention Name(s)
Rindopepimut (CDX-110) with GM-CSF
Intervention Description
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
Intervention Name(s)
KLH
Intervention Description
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.
Primary Outcome Measure Information:
Title
Groups 1 and 2: Progression-free survival rate
Description
Evaluate the antitumor activity of rindopepimut in adult patients with relapsed glioblastoma, as measured by the progression-free survival rate at 6 months post-Day 1 (PFS 6).
Time Frame
6 months post-Day 1
Title
Group 2C: Objective Response Rate
Description
Evaluate the anti-tumor activity of rindopepimut in adult patients with relapsed glioblastoma, as measured by the objective response rate (ORR) for patients with measurable disease at study entry.
Time Frame
Every 8 weeks from Day 1 through progression or initiation of other anti-cancer therapy
Secondary Outcome Measure Information:
Title
Safety and Tolerability
Description
Safety and tolerability will be evaluated by comparing the treatment regimens in regards to vital sign measurements, physical and neurological examinations, adverse events reporting, and Karnofsky performance status
Time Frame
Until 28 days or initiation of other anti-cancer treatment, whichever is first
Title
Anti-tumor activity
Description
Evaluated by comparing the treatment regimens for anti-tumor activity, including objective response rate, overall progression free survival (PFS), and overall survival (OS) for Groups 1 and 2; and PFS6, overall PFS, and OS for Group 2C.
Time Frame
During treatment and every 8 weeks through follow up
Title
EGFRvIII-specific immune response
Description
Characterize the EGFRvIII specific immune response to rindopepimut.
Time Frame
Several times during the first month of treatment and then approximately every 8 weeks until treatment is stopped.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Among other criteria, patients must meet the following conditions to be eligible for the study:
Age ≥18 years of age.
Histologic diagnosis of glioblastoma (WHO Grade IV).
Documented EGFRvlll positive tumor status (central lab confirmation).
First or second relapse of de novo glioblastoma or first diagnosis or first relapse of secondary glioblastoma.
Previous treatment must include surgery, conventional radiation therapy and temozolomide (TMZ).
Screening MRI must be obtained at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy.
KPS of ≥ 70%.
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.
Evaluable disease in Groups 1 and 2; measurable disease in Group 2C
Life expectancy > 12 weeks.
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:
Subjects unable to undergo an MRI with contrast.
History, presence, or suspicion of metastatic disease
Prior receipt of vaccination against EGFRvIII.
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.
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.
Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
Evidence of recent hemorrhage on screening MRI of the brain
Evidence of current drug or alcohol abuse.
Patients in Group 1 must not have received prior treatment with bevacizumab.
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
St. Joseph's Hospital and Medical Center / Barrow Neurological Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Kaiser Permanente Los Angeles Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
University of Southern California (USC) Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90089
Country
United States
Facility Name
UC Irvine Chao Family Comprehensive Cancer Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford Cancer Institute, Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Colorado, Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Memorial Cancer Institute
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Orlando Health, Inc.
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Tampa General Hospital
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Piedmont Atlanta Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Atlanta Cancer Care
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States
Facility Name
NorthShore University Health System
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
The Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Dana-Farber Cancer Institute and Mass General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Sparrow Cancer Center
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48912
Country
United States
Facility Name
John Nasseff Neuroscience Institute, Abbott Northwestern Hospital, 800 e. 28th Str. MR
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
New Jersey Neuroscience Institute JFK Medical Center
City
Edison
State/Province
New Jersey
ZIP/Postal Code
08818
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Dent Neurologic Institute, 3980 Sheridan Dr, 3rd Flr Clinical Rsch
City
Amherst
State/Province
New York
ZIP/Postal Code
14226
Country
United States
Facility Name
The Long Island Brain Tumor Center at Neurology Surgery, P.C.
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Stony Brook University Hospital
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794-8121
Country
United States
Facility Name
The Preston Robert Tisch Brain Tumor Center; Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Wake Forest Baptist Health
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
University of Cincinnati Cancer Institute
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Legacy Research Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97232
Country
United States
Facility Name
Lehigh Valley Hospital-John and Dorothy Morgan Cancer Center
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18103
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Texas Oncology Midtown
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Baylor Research Institute
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
UT Health Science Center, Houston Memorial Hermann Hospital, 6400 Fannin Street, #2800
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Utah Cancer Specialists
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84116
Country
United States
Facility Name
Swedish Neuroscience Research
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
32034072
Citation
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.
Results Reference
result
PubMed Identifier
26670466
Citation
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.
Results Reference
derived
Learn more about this trial
A Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma
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