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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:
Information provided by (Responsible Party):
Celldex Therapeutics

Tracking Information
First Submitted Date  ICMJE December 21, 2011
First Posted Date  ICMJE December 23, 2011
Last Update Posted Date February 17, 2020
Study Start Date  ICMJE December 2011
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 15, 2013)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 22, 2011)
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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 15, 2013)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2011)
  • 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, and overall survival (OS).
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma
Official Title  ICMJE A Phase II Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma
  • Small Cell Glioblastoma
  • Giant Cell Glioblastoma
  • Gliosarcoma
  • Glioblastoma With Oligodendroglial Component
  • Recurrent Glioblastoma
  • Relapsed Glioblastoma
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Bevacizumab
    • Drug: Rindopepimut (CDX-110) with 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.
    Interventions:
    • Drug: Bevacizumab
    • Drug: 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).
    Interventions:
    • Drug: Bevacizumab
    • Drug: Rindopepimut (CDX-110) with GM-CSF
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 30, 2016)
127
Original Estimated Enrollment  ICMJE
 (submitted: December 22, 2011)
95
Actual Study Completion Date  ICMJE May 17, 2016
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01498328
Other Study ID Numbers  ICMJE CDX110-06
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celldex Therapeutics
Study Sponsor  ICMJE Celldex Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Celldex Therapeutics
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP