Condition or disease | Intervention/treatment | Phase |
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Glioblastoma | Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs containing GM CSF Drug: Temozolomide Biological: Tetanus-Diphtheria Toxoid (Td) Biological: GM-CSF Biological: 111-Indium-labeling of Cells for in vivo Trafficking Studies | Phase 2 |
Approximately 64 patients with resected, newly-diagnosed WHO Grade IV glioma who are CMV positive and in which the Methylguanine Methyltransferase (MGMT) is not methylated will be accrued to this study before standard of care radiation therapy (RT) and concurrent TMZ, with the goal of treating 48 patients with dose-intensified temozolomide and pp65 loaded dendritic cell vaccine after completion of standard RT and TMZ.
All enrolled patients will undergo a leukapheresis for the generation of DCs. Patients will then receive approximately 6 weeks of the standard of care radiation therapy (RT) and concurrent TMZ at a standard targeted dose of 75 mg/m2/day. For patients whose initial leukapheresis yields less than 3 vaccines, repeat leukapheresis may be obtained. At the post-RT clinic visit, a single post-RT cycle of dose-intensified TMZ (100 mg/m2/day for 21 days) will be given. On day 23 (± 2 days) of the cycle, patients will receive the first of 3 pp65 DC vaccines. Vaccines #1-3 will be given every two weeks (± 2 days). All patients will receive up to a total of 10 DC vaccines, with vaccines administered every 35 days (± 7 days) after the third vaccine, given bilaterally at the groin site unless progression occurs with no further cycles of TMZ. DC vaccines will be given intradermally (i.d.) and divided equally to both inguinal regions. Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Patients will undergo leukapheresis again for immunologic monitoring with a specific assessment of baseline antigen-specific cellular and humoral immune responses if needed for further DC generations 14 (± 2) days after vaccine #3. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2, the vaccine site will receive a pre-conditioning intradermal injection of Td. Up to 16 patients will receive 111-Indium labeled DCs at the 4th vaccine followed by SPECT/CT imaging immediately, and at 1 and 2 days after injections.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 48 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | Newly-diagnosed WHO Grade IV glioma patients with their tumor resected and found to be MGMT unmethylated will be accrued to this study before the standard of care chemoradiation with the goal of treating with dose-intensified TMZ and pp65 loaded dendritic cell vaccine after completion of the standard of care chemoradiation. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | I-ATTAC: Improved Anti-Tumor Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma |
Actual Study Start Date : | September 30, 2019 |
Estimated Primary Completion Date : | December 2023 |
Estimated Study Completion Date : | December 2023 |
Arm | Intervention/treatment |
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Experimental: DC vaccination with Td preconditioning and GM CSF
This single-arm phase II study will assess the impact of tetanus pre-conditioning and adjuvant GM-CSF on overall survival of newly diagnosed GBM patients who have undergone definitive resection, are unmethylated, and completed standard temozolomide and radiation treatment. All enrolled patients will undergo a leukapheresis for the generation of DCs. Patients will then receive approximately 6 weeks of standard of care radiation therapy (RT) and concurrent TMZ. A single post-RT cycle of dose intensified TMZ (100 mg/m2/day for 21 days) will then be given. On day 23 (± 2 days) of the cycle, patients will receive the first of 3 pp65 DC vaccines every 2 weeks. All patients will receive up to a total of 10 DC vaccines
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Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs containing GM CSF
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:
Drug: Temozolomide Temozolomide is a chemotherapy drug given to all enrolled patients at the post-RT clinic visit as dose-intensified TMZ (100 mg/m2/day for 21 days).
Other Names:
Biological: Tetanus-Diphtheria Toxoid (Td) Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2 the vaccine site will receive a pre-conditioning intradermal injection of Td (1 flocculation unit (Lf), in 0.3 mL of saline for a total of 0.4 mL).
Other Names:
Biological: GM-CSF Granulocyte macrophage-colony stimulating factor (GM-CSF) is a sterile, white, preservative-free lyophilized powder in a vial containing 250 mcg that will be reconstituted in 0.5 mL of sterile water for injection and used as an adjuvant with the DC vaccine.
Other Names:
Biological: 111-Indium-labeling of Cells for in vivo Trafficking Studies 111-In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs labeled with 111-In (50 μCi / 5 x 10^7 DCs) and given i.d. as the fourth vaccine. In up to 16 patients, the fourth vaccine will be labeled with 111-In (50 μCi / 5 x 10^7 DCs) prior to injection.
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Severe, active comorbidity, including any of the following:
Contact: Mustafa Khasraw, MBChB, MD, FRCP, FRACP | 919-684-5301 | dukebrain1@dm.duke.edu | |
Contact: Nicole Cort | 919-684-5301 | dukebrain1@dm.duke.edu |
United States, North Carolina | |
Duke University Medical Center | Recruiting |
Durham, North Carolina, United States, 27710 | |
Contact: Mustafa Khasraw, MBChB, MD, FRCP, FRACP 919-684-5301 dukebrain1@dm.duke.edu | |
Contact: Nicole Cort 919-684-5301 dukebrain1@dm.duke.edu |
Principal Investigator: | Mustafa Khasraw, MBChB, MD, FRCP, FRACP | Duke University |
Tracking Information | |||||||||
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First Submitted Date ICMJE | April 19, 2019 | ||||||||
First Posted Date ICMJE | April 25, 2019 | ||||||||
Last Update Posted Date | March 26, 2021 | ||||||||
Actual Study Start Date ICMJE | September 30, 2019 | ||||||||
Estimated Primary Completion Date | December 2023 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Median overall survival of subjects receiving Td pre-conditioning with GM-CSF [ Time Frame: 5 years ] Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up has OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma | ||||||||
Official Title ICMJE | I-ATTAC: Improved Anti-Tumor Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma | ||||||||
Brief Summary | This single-arm phase II study will assess the impact of tetanus pre-conditioning and adjuvant Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) on overall survival of patients newly diagnosed with World Health Organization (WHO) Grade IV glioblastoma who have undergone definitive tumor resection, are cytomegalvirus (CMV) positive and unmethylated, and completed standard temozolomide (TMZ) and radiation treatment. After completion of the standard of care radiotherapy with concurrent TMZ, patients will receive 1 cycle of dose-intensified TMZ followed by pp65-loaded dendritic cell (DC) vaccination beginning on day 23. | ||||||||
Detailed Description |
Approximately 64 patients with resected, newly-diagnosed WHO Grade IV glioma who are CMV positive and in which the Methylguanine Methyltransferase (MGMT) is not methylated will be accrued to this study before standard of care radiation therapy (RT) and concurrent TMZ, with the goal of treating 48 patients with dose-intensified temozolomide and pp65 loaded dendritic cell vaccine after completion of standard RT and TMZ. All enrolled patients will undergo a leukapheresis for the generation of DCs. Patients will then receive approximately 6 weeks of the standard of care radiation therapy (RT) and concurrent TMZ at a standard targeted dose of 75 mg/m2/day. For patients whose initial leukapheresis yields less than 3 vaccines, repeat leukapheresis may be obtained. At the post-RT clinic visit, a single post-RT cycle of dose-intensified TMZ (100 mg/m2/day for 21 days) will be given. On day 23 (± 2 days) of the cycle, patients will receive the first of 3 pp65 DC vaccines. Vaccines #1-3 will be given every two weeks (± 2 days). All patients will receive up to a total of 10 DC vaccines, with vaccines administered every 35 days (± 7 days) after the third vaccine, given bilaterally at the groin site unless progression occurs with no further cycles of TMZ. DC vaccines will be given intradermally (i.d.) and divided equally to both inguinal regions. Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Patients will undergo leukapheresis again for immunologic monitoring with a specific assessment of baseline antigen-specific cellular and humoral immune responses if needed for further DC generations 14 (± 2) days after vaccine #3. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2, the vaccine site will receive a pre-conditioning intradermal injection of Td. Up to 16 patients will receive 111-Indium labeled DCs at the 4th vaccine followed by SPECT/CT imaging immediately, and at 1 and 2 days after injections. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Intervention Model Description: Newly-diagnosed WHO Grade IV glioma patients with their tumor resected and found to be MGMT unmethylated will be accrued to this study before the standard of care chemoradiation with the goal of treating with dose-intensified TMZ and pp65 loaded dendritic cell vaccine after completion of the standard of care chemoradiation. Masking: None (Open Label)Primary Purpose: Treatment |
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Condition ICMJE | Glioblastoma | ||||||||
Intervention ICMJE |
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Study Arms ICMJE | Experimental: DC vaccination with Td preconditioning and GM CSF
This single-arm phase II study will assess the impact of tetanus pre-conditioning and adjuvant GM-CSF on overall survival of newly diagnosed GBM patients who have undergone definitive resection, are unmethylated, and completed standard temozolomide and radiation treatment. All enrolled patients will undergo a leukapheresis for the generation of DCs. Patients will then receive approximately 6 weeks of standard of care radiation therapy (RT) and concurrent TMZ. A single post-RT cycle of dose intensified TMZ (100 mg/m2/day for 21 days) will then be given. On day 23 (± 2 days) of the cycle, patients will receive the first of 3 pp65 DC vaccines every 2 weeks. All patients will receive up to a total of 10 DC vaccines
Interventions:
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
48 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | December 2023 | ||||||||
Estimated Primary Completion Date | December 2023 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03927222 | ||||||||
Other Study ID Numbers ICMJE | Pro00090683 | ||||||||
Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Gary Archer Ph.D., Duke University | ||||||||
Study Sponsor ICMJE | Gary Archer Ph.D. | ||||||||
Collaborators ICMJE | Not Provided | ||||||||
Investigators ICMJE |
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PRS Account | Duke University | ||||||||
Verification Date | March 2021 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |