A Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma (ReACT)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01498328 |
|
Recruitment Status :
Completed
First Posted : December 23, 2011
Last Update Posted : February 17, 2020
|
Sponsor:
Celldex Therapeutics
Information provided by (Responsible Party):
Celldex Therapeutics
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial. More info ...
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 Type : | Interventional (Clinical Trial) |
| 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 : | December 2011 |
| Actual Primary Completion Date : | April 2015 |
| Actual Study Completion Date : | May 17, 2016 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Bevacizumab
| 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 Name: 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 Name: 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 Name: 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. |
Primary Outcome Measures :
- Groups 1 and 2: Progression-free survival rate [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01498328
Locations
Show 45 study locations
Sponsors and Collaborators
Celldex Therapeutics
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Celldex Therapeutics |
| ClinicalTrials.gov Identifier: | NCT01498328 |
| Other Study ID Numbers: |
CDX110-06 |
| First Posted: | December 23, 2011 Key Record Dates |
| Last Update Posted: | February 17, 2020 |
| Last Verified: | April 2017 |
Keywords provided by Celldex Therapeutics:
|
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 |
Additional relevant MeSH terms:
|
Glioblastoma Gliosarcoma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial |
Neoplasms, Nerve Tissue Bevacizumab Rindopepimut Antineoplastic Agents, Immunological Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors |