DC Migration Study for Newly-Diagnosed GBM

NCT02366728 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00054740
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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-conditioning 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.

Conditions

Glioblastoma; Astrocytoma, Grade IV; Giant Cell Glioblastoma; Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (4)

• Median Overall Survival

  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.

  Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

• Percentage of 111In-labeled Dendritic Cells Migrating to the Inguinal Lymph Nodes

  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.

  For each patient, migration studies will occur after vaccination #4 which occurs approximately 7 months after study consent.

• Median Overall Survival in CMV Positive Participants

  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.

  Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

• Median Overall Survival in CMV Negative Participants

  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.

  Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

Secondary Outcomes (3)

• Median Progression-free Survival

  Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

• Median Progression-free Survival in CMV Positive Participants

  Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

• Median Progression-free Survival in CMV Negative Participants

  Up to 72 months (from the time of randomization of the first patient until approximately 31 months after randomization of the last patient)

Study Arms (3)

Group I: Unpulsed DC pre-conditioning

EXPERIMENTAL

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 4th human CMV pp65-LAMP mRNA-pulsed autologous DCs vaccine. pp65 DC Vaccine #4 is 111In-labeled DCs for migration studies.

Biological: Unpulsed DCs; Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs; Biological: 111In-labeled DCs; Drug: Temozolomide; Drug: Saline

Group II: Tetanus pre-conditioning

EXPERIMENTAL

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 4th human CMV pp65-LAMP mRNA-pulsed autologous DCs vaccine. pp65 DC Vaccine #4 is 111In-labeled DCs for migration studies.

Biological: Td; Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs; Biological: 111In-labeled DCs; Drug: Temozolomide; Drug: Saline

Group III: Basiliximab and Tetanus pre-conditioning

EXPERIMENTAL

Basiliximab infusions prior to human CMV pp65-LAMP mRNA-pulsed autologous DCs 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 4th human CMV pp65-LAMP mRNA-pulsed autologous DCs vaccine.

Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs; Drug: Temozolomide; Drug: Saline; Drug: Basiliximab

Interventions

Unpulsed DCs BIOLOGICAL

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.

Also known as: Unpulsed DCs pre-conditioning

Group I: Unpulsed DC pre-conditioning

Td BIOLOGICAL

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.

Also known as: Td toxoid, Td pre-conditioning

Group II: Tetanus pre-conditioning

Human CMV pp65-LAMP mRNA-pulsed autologous DCs BIOLOGICAL

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.

Also known as: CMV-specific dendritic cell vaccine, DCs

Group I: Unpulsed DC pre-conditioning; Group II: Tetanus pre-conditioning; Group III: Basiliximab and Tetanus pre-conditioning

111In-labeled DCs BIOLOGICAL

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.

Group I: Unpulsed DC pre-conditioning; Group II: Tetanus pre-conditioning

Temozolomide DRUG

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.

Also known as: Temodar, TMZ

Group I: Unpulsed DC pre-conditioning; Group II: Tetanus pre-conditioning; Group III: Basiliximab and Tetanus pre-conditioning

Saline DRUG

0.4mL of saline given in the opposite groin 1 day before the fourth vaccine in all groups

Group I: Unpulsed DC pre-conditioning; Group II: Tetanus pre-conditioning; Group III: Basiliximab and Tetanus pre-conditioning

Basiliximab DRUG

Group III will receive basiliximab infusions (20 mg I.V) 1 week before the first vaccine and 1 week before the second vaccine.

Group III: Basiliximab and Tetanus pre-conditioning

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years of age
• WHO Grade IV Glioma with definitive resection prior to enrollment, with residual radiographic contrast enhancing disease on the post-operative 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%.
• 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 procedure (leukapheresis).
• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Mustafa Khasraw, MBChB, MD, FRCP, FRACP: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide; Sodium Chloride; Basiliximab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Mustafa Khasraw, M.D.
• Organization: Duke University

mustafa.khasraw@duke.edu

919-668-6688

Study Officials

• Dina Randazzo, DO

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 28, 2014
• First Posted: February 19, 2015
• Study Start: October 12, 2015
• Primary Completion: October 31, 2020
• Study Completion: October 31, 2020
• Last Updated: June 8, 2023
• Results First Posted: February 1, 2022

Record last verified: 2023-06

Locations

US (1)