RECRUITING

D2C7-IT + 2141-V11 Combination Post-resection in RGBM

Conditions

Recurrent Glioblastoma IDH Wildtype D2C7 D2C7-IT 2141-V11 Pro00115800 GBM Glioblastoma convection-enhanced delivery CED IDHwt

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to assess the safety and efficacy of the combination of D2C7-IT+2141-V11 administered in the non-enhancing tumor of patients with resected recurrent glioblastoma (rGBM) via convection enhanced delivery (CED), followed by subcutaneous cervical perilymphatic injections (CPLIs) of 2141-V11 2 and 4 weeks post infusion, then every 3 weeks for a year, and every 4-6 weeks thereafter if patients benefit from therapy.

Official Title

Clinical Trial of D2C7-IT + 2141-V11 Combination Immunotherapy Administered Via Convection Enhanced Delivery in Non-enhancing Tumor Post-resection of Recurrent Glioblastoma, Followed by Cervical Perilymphatic Subcutaneous Injections of 2141-V11

Quick Facts

Study Start:2025-03-17

Study Completion:2030-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06455605

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age ≥ 18 years old at the time of entry into the study 2. Histopathologically confirmed WHO grade 4 IDHwt GBM (high grade glioma with molecular features of glioblastoma will be eligible) 3. Karnofsky Performance Score (KPS) ≥ 70% 4. Hemoglobin ≥ 9 g/dl prior to biopsy 5. Platelet count ≥ 100,000/µl unsupported is necessary for eligibility on the study; however, because of risks of intracranial hemorrhage with catheter placement, platelet count ≥ 125,000/µl is required for the patient to undergo biopsy and catheter insertion, which can be attained with the help of platelet transfusion. 6. Neutrophil count ≥ 1000 prior to biopsy 7. Creatinine ≤ 1.5 x normal range prior to biopsy 8. Total bilirubin ≤ 1.5 x ULN prior to biopsy (Exception: Participant has known or suspected Gilbert's Syndrome for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.) 9. AST/ALT ≤ 2.5 x ULN 10. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy. Patients with prior history of thrombosis/embolism are allowed to be on anticoagulation, understanding that anticoagulation will be held in the perioperative period per the neurosurgical team's recommendations. Low molecular weight heparin (LMWH) is preferred. If a patient is on warfarin, the international normalized ratio (INR) is to be obtained and value should be below 2.0 prior to surgical resection and biopsy. 11. Patient must have undergone resection per the recommendation of their treating physician 3-5 weeks prior to administration of D2C7-IT, and the presence of recurrent tumor must have been confirmed by histopathological analysis. 12. Able to undergo brain MRI with and without contrast 13. Patient or partner(s) meets one of the following criteria: 1. Non-childbearing potential (i.e. not sexually active, physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile, or any male who has had a vasectomy). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Postmenopausal for purposes of this study is defined as 1 year without menses.; or 2. Childbearing potential and agrees to use one of the following methods of birth control: approved hormonal contraceptives (e.g. birth control pills, patches, implants, or infusions), an intrauterine device, or a barrier method of contraception (e.g. a condom or diaphragm) used with spermicide. 14. A signed ICF approved by the IRB will be required for patient enrollment into the study. Patients must be able to read and understand the ICF and must sign the ICF indicating that they are aware of the investigational nature of this study	1. Females who are pregnant (negative pregnancy test at screening visit) or breast- feeding 2. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate 3. Patients with severe, active co-morbidity, defined as follow: 1. Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax \> 99.5°F/37.5°C) 2. Patients with known immunosuppressive disease or known human immunodeficiency virus infection 3. Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4) 4. Patients with known lung (forced expiratory volume in the first second of expiration (FEV1) \< 50%) disease or uncontrolled diabetes mellitus 5. Patients with albumin allergy 4. Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks \[except for nitrosourea (6 weeks), or metronomic dosed chemotherapy such as daily etoposide or cyclophosphamide (1 week)\] prior to starting the study drug unless patients have recovered from side effects of such therapy 5. Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy 6. Patients may not have received treatment with tumor treating fields (e.g., Optune®) * 1 week prior to starting the study drug 7. Patients may not be less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation 8. Patients who have not completed all standard of care treatments, including surgical procedure and radiation therapy (Please note: For patients under 65 years old, standard radiation therapy is typically at least 59 Gy in 30 fractions over 6 weeks. For patients 65 years or older, standard RT is often reduced to a minimum 40 Gy in 15 fractions over 3 weeks.) 1. If the MGMT promoter in their tumor is known to be unmethylated, patients are not mandated to have received chemotherapy prior to participating in this trial 2. If the MGMT promoter in their tumor is known to be methylated or the MGMT promoter methylation status is unknown at time of screening, patients must have received at least one chemotherapy regimen prior to participating in this trial 9. Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord; radiological evidence of active (growing) disease (active multifocal disease); extensive subependymal disease (tumor touching subependymal space is allowed); tumor crossing the midline or leptomeningeal disease 10. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the D2C7-IT infusion 11. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups) 12. Patients with 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 13. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months 14. Patients who cannot undergo MRI due to obesity or to having certain metal in their bodies (i.e. pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates)

Inclusion Criteria

Exclusion Criteria

1. Age ≥ 18 years old at the time of entry into the study
2. Histopathologically confirmed WHO grade 4 IDHwt GBM (high grade glioma with molecular features of glioblastoma will be eligible)
3. Karnofsky Performance Score (KPS) ≥ 70%
4. Hemoglobin ≥ 9 g/dl prior to biopsy
5. Platelet count ≥ 100,000/µl unsupported is necessary for eligibility on the study; however, because of risks of intracranial hemorrhage with catheter placement, platelet count ≥ 125,000/µl is required for the patient to undergo biopsy and catheter insertion, which can be attained with the help of platelet transfusion.
6. Neutrophil count ≥ 1000 prior to biopsy
7. Creatinine ≤ 1.5 x normal range prior to biopsy
8. Total bilirubin ≤ 1.5 x ULN prior to biopsy (Exception: Participant has known or suspected Gilbert's Syndrome for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)
9. AST/ALT ≤ 2.5 x ULN
10. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy. Patients with prior history of thrombosis/embolism are allowed to be on anticoagulation, understanding that anticoagulation will be held in the perioperative period per the neurosurgical team's recommendations. Low molecular weight heparin (LMWH) is preferred. If a patient is on warfarin, the international normalized ratio (INR) is to be obtained and value should be below 2.0 prior to surgical resection and biopsy.
11. Patient must have undergone resection per the recommendation of their treating physician 3-5 weeks prior to administration of D2C7-IT, and the presence of recurrent tumor must have been confirmed by histopathological analysis.
12. Able to undergo brain MRI with and without contrast
13. Patient or partner(s) meets one of the following criteria:
1. Non-childbearing potential (i.e. not sexually active, physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile, or any male who has had a vasectomy). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Postmenopausal for purposes of this study is defined as 1 year without menses.; or
2. Childbearing potential and agrees to use one of the following methods of birth control: approved hormonal contraceptives (e.g. birth control pills, patches, implants, or infusions), an intrauterine device, or a barrier method of contraception (e.g. a condom or diaphragm) used with spermicide.
14. A signed ICF approved by the IRB will be required for patient enrollment into the study. Patients must be able to read and understand the ICF and must sign the ICF indicating that they are aware of the investigational nature of this study

1. Females who are pregnant (negative pregnancy test at screening visit) or breast- feeding
2. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate
3. Patients with severe, active co-morbidity, defined as follow:
1. Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax \> 99.5°F/37.5°C)
2. Patients with known immunosuppressive disease or known human immunodeficiency virus infection
3. Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
4. Patients with known lung (forced expiratory volume in the first second of expiration (FEV1) \< 50%) disease or uncontrolled diabetes mellitus
5. Patients with albumin allergy
4. Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks \[except for nitrosourea (6 weeks), or metronomic dosed chemotherapy such as daily etoposide or cyclophosphamide (1 week)\] prior to starting the study drug unless patients have recovered from side effects of such therapy
5. Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy
6. Patients may not have received treatment with tumor treating fields (e.g., Optune®)
* 1 week prior to starting the study drug
7. Patients may not be less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation
8. Patients who have not completed all standard of care treatments, including surgical procedure and radiation therapy (Please note: For patients under 65 years old, standard radiation therapy is typically at least 59 Gy in 30 fractions over 6 weeks. For patients 65 years or older, standard RT is often reduced to a minimum 40 Gy in 15 fractions over 3 weeks.)
1. If the MGMT promoter in their tumor is known to be unmethylated, patients are not mandated to have received chemotherapy prior to participating in this trial
2. If the MGMT promoter in their tumor is known to be methylated or the MGMT promoter methylation status is unknown at time of screening, patients must have received at least one chemotherapy regimen prior to participating in this trial
9. Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord; radiological evidence of active (growing) disease (active multifocal disease); extensive subependymal disease (tumor touching subependymal space is allowed); tumor crossing the midline or leptomeningeal disease
10. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the D2C7-IT infusion
11. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
12. Patients with 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
13. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months
14. Patients who cannot undergo MRI due to obesity or to having certain metal in their bodies (i.e. pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates)

Contacts and Locations

Study Contact

Annick Desjardins, MD

CONTACT

919-684-5301

dukebrain1@dm.duke.edu

Stevie Threatt

CONTACT

919-684-5301

dukebrain1@dm.duke.edu

Principal Investigator

Annick Desjardins, MD

PRINCIPAL_INVESTIGATOR

Duke University

Study Locations (Sites)

Duke University Medical Center

Durham, North Carolina, 27710

United States

Collaborators and Investigators

Sponsor: Darell Bigner

Annick Desjardins, MD, PRINCIPAL_INVESTIGATOR, Duke University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-03-17

Study Completion Date2030-01-31

Study Record Updates

Study Start Date2025-03-17

Study Completion Date2030-01-31

Terms related to this study

Keywords Provided by Researchers

D2C7
D2C7-IT
2141-V11
Pro00115800
GBM
Glioblastoma
convection-enhanced delivery
CED
IDHwt

Additional Relevant MeSH Terms

Recurrent Glioblastoma IDH Wildtype