Glioblastoma Clinical Trial
Official title:
A Phase 1b / 2 Open-label Study to Investigate the Safety, Tolerance and Efficacy of Drug Resistant Immunotherapy (DRI) With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide (TMZ) in Subjects With Recurrent or Newly Diagnosed Glioblastoma
This multicenter, Phase 1b/2 study is being conducted to determine if the experimental cell therapy is safe, tolerable and can delay the return of cancer in patients with a newly diagnosed or recurrent glioblastoma multiforme (GBM) in combination with standard chemotherapy treatment temozolomide (TMZ). If there is a 25% or greater improvement in survival in this study then the therapy should be studied further.
Status | Recruiting |
Enrollment | 120 |
Est. completion date | December 2025 |
Est. primary completion date | December 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Subjects with histologically or cytologically confirmed history of IDH-wild type glioblastoma - Phase 1b and Arm B of Phase 2: Subjects must have completed no more than one standard therapy for glioblastoma, have received no prior Avastin® therapy (unless solely used for edema management) and be eligible for resection - Arms A and C: Subjects must have newly diagnosed, treatment naïve glioblastoma - Phase 1b and Arm B and Arm C: Subjects must have a partially matched haploidentical or matched related donor. - Subjects with magnetic resonance imaging (MRI) features consistent with and suspicious for recurrent malignant glioma in Phase 1b and Arm B. - Agreeable to inserting and maintaining a Rickham catheter. - = 18 years of age. - Karnofsky Performance Status = 70% - Female subjects of childbearing potential must have a negative urine/serum pregnancy test within 72 hours of study enrollment. Female subjects of childbearing potential are those who have not been surgically sterilized or have not been free of menses for > 2 years. - Male subjects and their female partners and female subjects of childbearing potential must be willing to use a combination of two methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study. Exclusion Criteria: - Subject in Arm A or donor from Phase 1b, Arms B, and Arm C received vaccinations within 4 weeks or underwent surgery (major or minor) within 72 hours before leukapheresis collection. - Cellular immunotherapy or gene therapy or within six weeks prior to entering the study, surgical resection or alkylating agent chemotherapy within four weeks prior to entering the study, receiving tumor treating fields (TTF) Optune therapy, or have received experimental immunotherapy at any time - Subjects receiving any other investigational agents concurrently while on study. - Have not recovered from adverse events (= Grade 1) from previously administered therapy. Subjects with alopecia unless of immune origin are an exception to this criterion and may qualify for this study - Have received prior treatment with an allogeneic therapy, including bone marrow or solid tumor transplant. - Concurrent malignancy or an active second malignancy. Subjects with a history of second malignancy must have no evidence of cancer for two years prior to enrolment or have a surgically cured cancer with low risk of recurrence to enroll. Discuss with medical monitor prior to enrolment. - Contraindication to the placement of an intracranial access device (Rickham catheter) at the time of surgery. - Prior history of encephalitis, multiple sclerosis, or other CNS infection <1 year prior to glioblastoma diagnosis. - Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or any other medical condition that precludes surgery. Also, medical/surgical/psychiatric illness/social situations that would limit compliance with study requirements or confound interpretation of safety and efficacy data. Subjects with a history of seizure as a result of their glioblastoma must be seizure free and on appropriate anti-epileptic medication for 3 weeks prior to dosing with the investigational agent. - Allergies/hypersensitivity to amino bisphosphonates such as Zoledronate®, Pamidronate® or similar. - History of HIV or active hepatitis even if well controlled or history of an autoimmune condition. |
Country | Name | City | State |
---|---|---|---|
United States | University of Alabama at Birmingham | Birmingham | Alabama |
United States | Cleveland Clinic | Cleveland | Ohio |
United States | Ohio State University Wexner Medical Center- James Cancer Center | Columbus | Ohio |
United States | UC San Diego Moores Cancer Center | La Jolla | California |
United States | UCLA | Los Angeles | California |
United States | University of Louisville Hospital/James Graham Brown Cancer Center | Louisville | Kentucky |
United States | Moffitt Cancer Center | Tampa | Florida |
Lead Sponsor | Collaborator |
---|---|
In8bio Inc. |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Autologous Phase 2, Arm A in newly diagnosed glioblastoma: 12-month overall survival (OS) rate | Date of first dose to date of death by any cause | 12 Months | |
Primary | Allogeneic Phase 1b, establishes the recommended phase 2 dose (RP2D) for phase 2 allogeneic arms and subject or product characteristics that will optimize manufacturing | <30% dose limiting toxicity (DLT) observed with dose | 28 days | |
Primary | Allogeneic Phase 2, Arm B confirmed recurrent glioblastoma, 9-month overall survival (OS) | Date of first dose to date of death by any cause | 9 Months | |
Primary | Allogeneic Phase 2, Arm C newly diagnosed glioblastoma, 12-month overall survival (OS) rate | Date of first dose to date of death by any cause | 12 Months | |
Secondary | Assessment of safety | Assessment of safety is based on total number of treatment emergent adverse events and serious adverse events Assessment of safety is also based on change from baseline of clinical laboratory tests including change in liver function tests, renal function and complete blood counts Assessment of safety is also based on change from baseline of vital signs including heart rate, blood pressure, temperature and pulse oximetry | 12 Months | |
Secondary | Assessment of tolerability | Assessment of tolerability is based on total number of treatment emergent adverse events and serious adverse events Assessment of tolerability is also based on change from baseline of clinical laboratory tests including change in liver function tests, renal function and complete blood counts Assessment of tolerability is also based on change from baseline of vital signs including heart rate, blood pressure, temperature and pulse oximetry | 12 Months | |
Secondary | Overall response rate (ORR) | ORR is defined as the rate of the best overall response as complete response (CR) or partial response (PR). | 12 Months | |
Secondary | Time to progression (TTP) | Time to progression will be defined as the time from first dose until objective tumor progression | 12 Months | |
Secondary | Progression free survival (PFS) | PFS will be defined as the time from first dose until objective tumor progression or death, whichever comes first. | 12 Months | |
Secondary | Definition of product characteristics | Product characteristics that predict for maximal success of product creation:
Age of donor ( <50 years of age, 51-65 years of age, >65 years of age), Total white blood cell count and individual immune cell count (neutrophils, T cells, gamma delta T cells) of the apheresis product, Time to infusion of manufactured product of apheresis material (1 month, 2months) |
12 Months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02768389 -
Feasibility Trial of the Modified Atkins Diet and Bevacizumab for Recurrent Glioblastoma
|
Early Phase 1 | |
Recruiting |
NCT05635734 -
Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma
|
Phase 1/Phase 2 | |
Completed |
NCT03679754 -
Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma, a Substudy to ATI001-102
|
Phase 1 | |
Completed |
NCT01250470 -
Vaccine Therapy and Sargramostim in Treating Patients With Malignant Glioma
|
Phase 1 | |
Terminated |
NCT03927222 -
Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma
|
Phase 2 | |
Recruiting |
NCT03897491 -
PD L 506 for Stereotactic Interstitial Photodynamic Therapy of Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma
|
Phase 2 | |
Active, not recruiting |
NCT03587038 -
OKN-007 in Combination With Adjuvant Temozolomide Chemoradiotherapy for Newly Diagnosed Glioblastoma
|
Phase 1 | |
Completed |
NCT01922076 -
Adavosertib and Local Radiation Therapy in Treating Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas
|
Phase 1 | |
Recruiting |
NCT04391062 -
Dose Finding for Intraoperative Photodynamic Therapy of Glioblastoma
|
Phase 2 | |
Active, not recruiting |
NCT03661723 -
Pembrolizumab and Reirradiation in Bevacizumab Naïve and Bevacizumab Resistant Recurrent Glioblastoma
|
Phase 2 | |
Active, not recruiting |
NCT02655601 -
Trial of Newly Diagnosed High Grade Glioma Treated With Concurrent Radiation Therapy, Temozolomide and BMX-001
|
Phase 2 | |
Completed |
NCT02206230 -
Trial of Hypofractionated Radiation Therapy for Glioblastoma
|
Phase 2 | |
Completed |
NCT03493932 -
Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade
|
Phase 1 | |
Terminated |
NCT02709889 -
Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT06058988 -
Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer
|
Phase 2 | |
Completed |
NCT03018288 -
Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM)
|
Phase 2 | |
Not yet recruiting |
NCT04552977 -
A Trail of Fluzoparil in Combination With Temozolomide in Patients With Recurrent Glioblastoma
|
Phase 2 | |
Withdrawn |
NCT03980249 -
Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells
|
Early Phase 1 | |
Withdrawn |
NCT02876003 -
Efficacy and Safety of G-202 in PSMA-Positive Glioblastoma
|
Phase 2 | |
Terminated |
NCT02905643 -
Discerning Pseudoprogression vs True Tumor Growth in GBMs
|