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DC Migration Study for Newly-Diagnosed GBM (ELEVATE)

This study is currently recruiting participants.
Verified June 2017 by Gary Archer Ph.D., Duke University Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02366728
First Posted: February 19, 2015
Last Update Posted: June 14, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Gary Archer Ph.D., Duke University Medical Center
  Purpose
This randomized phase II study will assess the impact of pre-conditioning on migration and survival among newly diagnosed glioblastoma (GBM) patients who have undergone definitive resection and completed standard temozolomide (TMZ) and radiation treatment, as well as the impact of tetanus pre-conditioning and basiliximab together on survival. After completing standard of care radiotherapy with concurrent TMZ, patients will be randomized to 1 of 3 treatment arms: 1). receive cytomegalovirus (CMV)-specific dendritic cell (DC) vaccines with unpulsed (not loaded) DC pre-coinditioning prior to the 4th vaccine; 2). receive CMV-specific DC vaccines with Tetanus-Diphtheria Toxoid (Td) pre-conditioning prior to the 4th vaccine; 3). receive basiliximab infusions prior to the 1st and 2nd DC vaccines along with Td pre-conditioning prior to the 4th vaccine. A permuted block randomization algorithm using a 1:1:1 allocation ratio will be used to assign patients to a treatment arm. Randomization will be stratified by CMV status (positive, negative), with the assignment to arms I and II being double-blinded. Effective March 2017, randomization to Group III has been terminated.

Condition Intervention Phase
Glioblastoma Astrocytoma, Grade IV Giant Cell Glioblastoma Glioblastoma Multiforme Biological: Unpulsed DCs Biological: Td Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs Biological: 111In-labeled DCs Drug: Temozolomide Drug: Saline Drug: Basiliximab Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Evaluation of Overcoming Limited Migration and Enhancing Cytomegalovirus-specific Dendritic Cell Vaccines With Adjuvant TEtanus Pre-conditioning in Patients With Newly-diagnosed Glioblastoma

Resource links provided by NLM:


Further study details as provided by Gary Archer Ph.D., Duke University Medical Center:

Primary Outcome Measures:
  • Median overall survival [ Time Frame: Approximately 60 months (from the time of randomization of the first patient until approximately 13 months after randomization of the last patient) ]
    Overall survival will be defined as the time in months between randomization and death, or last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.

  • Percentage of 111In-labeled dendritic cells migrating to the inguinal lymph nodes [ Time Frame: For each patient, migration studies will occur after vaccination #4 which occurs approximately 7 months after study consent. ]
    Within Groups I and II only, the percentage of 111In-labeled DCs migrating to the inguinal lymph nodes from the initial injection sites in the left and right groin at 48 hours post-vaccination #4 will be calculated. This analysis will be based on the first 12 patients in each arm (Group I and Group II) that receive vaccination #4.

  • Median overall survival in CMV positive participants [ Time Frame: Approximately 60 months (from the time of randomization of the first patient until approximately 13 months after randomization of the last patient) ]
    Median overall survival will be estimated in the subset of participants that are CMV positive. Overall survival will be defined as the time in months between randomization and death, or last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.

  • Median overall survival in CMV negative participants [ Time Frame: Approximately 60 months (from the time of randomization of the first patient until approximately 13 months after randomization of the last patient) ]
    Median overall survival will be estimated in the subset of participants that are CMV negative. Overall survival will be defined as the time in months between randomization and death, or last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.


Secondary Outcome Measures:
  • Median progression-free survival [ Time Frame: Approximately 60 months (from the time of randomization of the first patient until approximately 13 months after randomization of the last patient) ]
    Progression-free survival will be defined as the time in months between randomization and disease progression or death. Participants alive without disease progression will be censored at the time of their last follow-up. Kaplan-Meier methods will be used to estimate progression-free survival.

  • Median progression-free survival in CMV positive participants [ Time Frame: Approximately 60 months (from the time of randomization of the first patient until approximately 13 months after randomization of the last patient) ]
    Median progression-free survival will be estimated in the subset of participants that are CMV positive. Progression-free survival will be defined as the time in months between randomization and disease progression or death. Participants alive without disease progression will be censored at the time of their last follow-up. Kaplan-Meier methods will be used to estimate progression-free survival.

  • Median progression-free survival in CMV negative participants [ Time Frame: Approximately 60 months (from the time of randomization of the first patient until approximately 13 months after randomization of the last patient) ]
    Median progression-free survival will be estimated in the subset of participants that are CMV negative. Progression-free survival will be defined as the time in months between randomization and disease progression or death. Participants alive without disease progression will be censored at the time of their last follow-up. Kaplan-Meier methods will be used to estimate progression-free survival.


Estimated Enrollment: 100
Study Start Date: September 2015
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group I: Unpulsed DC pre-conditioning
0.4 mLs of 1 x 10^6 autologous unpulsed DCs in saline will be administered to a single side of the groin, and 0.4 mLs of saline administered to the contralateral side 1 day prior to the fourth human CMV pp65-LAMP mRNA-pulsed autologous DCs vaccine. pp65 DC Vaccine #4 is 111In-labeled DCs for migration studies. All patients will be vaccinated with pp65 DCs in conjunction with subsequent TMZ cycles every 5 ± 1 weeks for a total of 6 to 12 cycles after RT.
Biological: Unpulsed DCs
Patients in Group I will receive 1 x 10^6 autologous unpulsed DCs in saline administered to a single side of the groin intradermally 1 day before the fourth vaccine.
Other Name: Unpulsed DCs pre-conditioning
Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs
2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines.
Other Names:
  • CMV-specific dendritic cell vaccine
  • DCs
Biological: 111In-labeled DCs
111In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs will be labeled with 111In (50 μCi / 5 x 10^7 DCs) and given i.d. as fourth vaccine for Groups I and II only.
Drug: Temozolomide
Temozolomide is a standard chemotherapy given to all enrolled patients at a targeted dose of 150-200mg/m2/d for 5 days every 5 (± 1) weeks for a total of 6 to 12 cycles at the discretion of the treating oncologist.
Other Names:
  • Temodar
  • TMZ
Drug: Saline
0.4mL of saline given in the opposite groin 1 day before the fourth vaccine in all groups
Experimental: Group II: Tetanus pre-conditioning
Tetanus diptheria toxoid (Td), 1 flocculation unit, will be administered to a single side of the groin, and 0.4 mLs of saline administered to the contralateral side 1 day prior to the fourth human CMV pp65-LAMP mRNA-pulsed autologous DCs vaccine. pp65 DC Vaccine #4 is 111In-labeled DCs for migration studies.All patients will be vaccinated with pp65 DCs in conjunction with subsequent TMZ cycles every 5 ± 1 weeks for a total of 6 to 12 cycles after RT.
Biological: Td
Patients in Groups II and III will receive a single dose of Td toxoid (1 flocculation unit, Lf, in 0.4 mLs) administered to a single side of the groin given intradermally 1 day before the fourth vaccine.
Other Names:
  • Td toxoid
  • Td pre-conditioning
Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs
2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines.
Other Names:
  • CMV-specific dendritic cell vaccine
  • DCs
Biological: 111In-labeled DCs
111In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs will be labeled with 111In (50 μCi / 5 x 10^7 DCs) and given i.d. as fourth vaccine for Groups I and II only.
Drug: Temozolomide
Temozolomide is a standard chemotherapy given to all enrolled patients at a targeted dose of 150-200mg/m2/d for 5 days every 5 (± 1) weeks for a total of 6 to 12 cycles at the discretion of the treating oncologist.
Other Names:
  • Temodar
  • TMZ
Drug: Saline
0.4mL of saline given in the opposite groin 1 day before the fourth vaccine in all groups
Experimental: Group III: Basiliximab and Tetanus pre-conditioning
Basiliximab infusions prior to human CMV pp65-LAMP mRNA-pulsed autologous DC vaccines #1 and #2 with Td pre-conditioning 1 flocculation unit, will be administered to a single side of the groin, and 0.4 mLs of saline administered to the contralateral side 1 day prior to the fourth human CMV pp65-LAMP mRNA-pulsed autologous DCs vaccine. All patients will be vaccinated with pp65 DCs in conjunction with subsequent TMZ cycles every 5 ± 1 weeks for a total of 6 to 12 cycles after RT.
Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs
2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines.
Other Names:
  • CMV-specific dendritic cell vaccine
  • DCs
Drug: Temozolomide
Temozolomide is a standard chemotherapy given to all enrolled patients at a targeted dose of 150-200mg/m2/d for 5 days every 5 (± 1) weeks for a total of 6 to 12 cycles at the discretion of the treating oncologist.
Other Names:
  • Temodar
  • TMZ
Drug: Saline
0.4mL of saline given in the opposite groin 1 day before the fourth vaccine in all groups
Drug: Basiliximab
Group III will receive basiliximab infusions (20 mg I.V) 1 week before the first vaccine and 1 week before the second vaccine.

  Show Detailed Description

  Eligibility

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 to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years of age
  • WHO Grade IV Glioma with definitive resection prior to enrollment, with residual radiographic contrast enhancement on most recent CT or Magnetic Resonance Imaging (MRI) of <1 cm in maximal diameter in any axial plane
  • MRI post radiation therapy (RT) does not show progressive disease at time of randomization
  • Karnofsky Performance Status of > 80% and a Curran Group status of I-IV.
  • Hemoglobin ≥ 9.0 g/dl, Absolute Neutrophil Count ≥ 1,500 cells/µl, platelets ≥ 125,000 cells/µl
  • Serum creatinine ≤ 1.5 mg/dl, Serum Glutamic Oxaloacetic Transaminase & bilirubin ≤ 1.5 times upper limit of normal
  • Signed informed consent approved by the Institutional Review Board
  • Female patients must not be pregnant or breast-feeding. Female patients of childbearing potential (defined as < 2 years after last menstruation or not surgically sterile) must use a highly effective contraceptive method (allowed methods of birth control, [i.e. with a failure rate of < 1% per year] are implants, injectables, combined oral contraceptives, intra-uterine device [IUDs; only hormonal], sexual abstinence or vasectomized partner) during the trial & for a period of > 6 months following the last administration of trial drug(s). Female patients with an intact uterus (unless amenorrhea for the last 24 months) must have negative serum pregnancy test within 48 hours prior to first study treatment
  • Fertile male patients must agree to use a highly effective contraceptive method (allowed methods of birth control [i.e. with a failure rate of < 1% per year] include a female partner using implants, injectables, combined oral contraceptives, IUDs [only hormonal], sexual abstinence or prior vasectomy) during the trial & for a period of > 6 months following the last administration of trial drugs

Exclusion Criteria:

  • Pregnant or breast-feeding
  • Women of childbearing potential & men who are sexually active and not willing/able to use medically acceptable forms of contraception
  • Patients with known potentially anaphylactic allergic reactions to gadolinium-Diethylenetriaminepentaacetic Acid
  • Patients who cannot undergo MRI or SPECT due to obesity or to having certain metal in their bodies (specifically pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates)
  • Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of multifocal disease, or leptomeningeal disease
  • Severe, active comorbidity, including any of the following

    • Unstable angina and/or congestive heart failure requiring hospitalization
    • Transmural myocardial infarction within the last 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study initiation
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
    • Known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
    • Known Human Immunodeficiency Virus positive status
    • Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy
    • Active connective tissue disorders, such as lupus or scleroderma that, in the opinion of the treating physician, may put the patient at high risk for radiation toxicity
  • Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids;
  • Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin;
  • Patients are not permitted to have had any other conventional therapeutic intervention other than steroids prior to enrollment outside of standard of care chemotherapy & radiation therapy. Patients who receive previous inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies will be excluded
  • Current, recent (within 4 weeks of the administration of this study agent), or planned participation in an experimental drug study
  • Known history of autoimmune disease (with the exceptions of medically-controlled hypothyroidism and Type I Diabetes Mellitus)
  Contacts and Locations
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): NCT02366728


Contacts
Contact: Jordan Parker, MS 919-684-5301 dukebrain1@dm.duke.edu
Contact: Susan Boulton, RN, BSN 919-684-5301 dukebrain1@duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Jordan Parker, MS    919-684-5301    dukebrain1@dm.duke.edu   
Contact: Susan Boulton, RN, BSN    919-684-5301    dukebrain1@duke.edu   
Principal Investigator: Dina Randazzo, DO         
Sponsors and Collaborators
Gary Archer Ph.D.
Investigators
Principal Investigator: Dina Randazzo, DO Duke University
  More Information

Responsible Party: Gary Archer Ph.D., Assistant Professor, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT02366728     History of Changes
Other Study ID Numbers: Pro00054740
First Submitted: October 28, 2014
First Posted: February 19, 2015
Last Update Posted: June 14, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Vaccines
Basiliximab
Antibodies, Monoclonal
Temozolomide
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents