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

Sponsor

Celldex Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT01498328

Collaborator

(none)

127

Enrollment

Locations

Arms

53.5

Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Small Cell Glioblastoma Giant Cell Glioblastoma Gliosarcoma Glioblastoma With Oligodendroglial Component Recurrent Glioblastoma Relapsed Glioblastoma	Drug: Bevacizumab Drug: Rindopepimut (CDX-110) with GM-CSF Drug: KLH	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

127 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2011

Actual Primary Completion Date :

Apr 1, 2015

Actual Study Completion Date :

May 17, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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. Other Names: Avastin 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.
Experimental: 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.	Drug: 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. Other Names: Avastin 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.
Experimental: 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).	Drug: 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. Other Names: Avastin 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.

Arm

Intervention/Treatment

Experimental: 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.

Drug: 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.

Other Names:

Avastin

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.

Experimental: 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.

Drug: Bevacizumab

Other Names:

Avastin

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.

Experimental: 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).

Drug: Bevacizumab

Other Names:

Avastin

Drug: Rindopepimut (CDX-110) with GM-CSF

Outcome Measures

Primary Outcome Measures

Groups 1 and 2: Progression-free survival rate [6 months post-Day 1]
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 [Every 8 weeks from Day 1 through progression or initiation of other anti-cancer therapy]
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 [Until 28 days or initiation of other anti-cancer treatment, whichever is first]
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 [During treatment and every 8 weeks through follow up]
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 [Several times during the first month of treatment and then approximately every 8 weeks until treatment is stopped.]
Characterize the EGFRvIII specific immune response to rindopepimut.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	St. Joseph's Hospital and Medical Center / Barrow Neurological Institute	Phoenix	Arizona	United States	85013
3	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
4	University of Southern California (USC) Norris Comprehensive Cancer Center	Los Angeles	California	United States	90089
5	UC Irvine Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
6	University of California San Francisco	San Francisco	California	United States	94143
7	Stanford Cancer Institute, Stanford University	Stanford	California	United States	94305
8	University of Colorado, Denver	Aurora	Colorado	United States	80045
9	Memorial Cancer Institute	Hollywood	Florida	United States	33021
10	Orlando Health, Inc.	Orlando	Florida	United States	32806
11	Tampa General Hospital	Tampa	Florida	United States	33606
12	Piedmont Atlanta Hospital	Atlanta	Georgia	United States	30309
13	Atlanta Cancer Care	Atlanta	Georgia	United States	30342
14	Rush University Medical Center	Chicago	Illinois	United States	60612
15	University of Chicago	Chicago	Illinois	United States	60637-1470
16	NorthShore University Health System	Evanston	Illinois	United States	60201
17	The Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
18	Dana-Farber Cancer Institute and Mass General Hospital	Boston	Massachusetts	United States	02115
19	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
20	Sparrow Cancer Center	Lansing	Michigan	United States	48912
21	John Nasseff Neuroscience Institute, Abbott Northwestern Hospital, 800 e. 28th Str. MR	Minneapolis	Minnesota	United States	55407
22	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
23	New Jersey Neuroscience Institute JFK Medical Center	Edison	New Jersey	United States	08818
24	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
25	Dent Neurologic Institute, 3980 Sheridan Dr, 3rd Flr Clinical Rsch	Amherst	New York	United States	14226
26	The Long Island Brain Tumor Center at Neurology Surgery, P.C.	Commack	New York	United States	11725
27	University of Rochester Medical Center	Rochester	New York	United States	14642
28	Stony Brook University Hospital	Stony Brook	New York	United States	11794-8121
29	The Preston Robert Tisch Brain Tumor Center; Duke University Medical Center	Durham	North Carolina	United States	27710
30	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
31	University of Cincinnati Cancer Institute	Cincinnati	Ohio	United States	45267
32	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106
33	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195
34	Legacy Research Institute	Portland	Oregon	United States	97232
35	Lehigh Valley Hospital-John and Dorothy Morgan Cancer Center	Allentown	Pennsylvania	United States	18103
36	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
37	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
38	Rhode Island Hospital	Providence	Rhode Island	United States	02903
39	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
40	Texas Oncology Midtown	Austin	Texas	United States	78705
41	Baylor Research Institute	Dallas	Texas	United States	75246
42	UT Health Science Center, Houston Memorial Hermann Hospital, 6400 Fannin Street, #2800	Houston	Texas	United States	77030
43	Utah Cancer Specialists	Salt Lake City	Utah	United States	84116
44	Swedish Neuroscience Research	Seattle	Washington	United States	98122
45	University of Washington Medical Center	Seattle	Washington	United States	98195