RECRUITING

D2C7-IT and 2141-V11 in Newly Diagnosed GBM Patients

Conditions

Newly Diagnosed MGMT Unmethylated Glioblastoma D2C7 D2C7-IT 2141-V11 Pro00110119 GBM Glioblastoma convection-enhanced delivery CED MGMT unmethylated

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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 research study is to determine the safety and efficacy of administering a single intracerebral (within the brain) dose of investigational compounds called D2C7-immunotoxin (IT) and 2141-V11 in residual disease (within tumor margins) after surgery, followed by later repeated injections of 2141-V11 in the subcutaneous area (under the skin) around the lymph nodes of the head and neck for adults newly diagnosed with a type of cancerous brain tumor called glioblastoma. The word "investigational" means the study drugs are still being tested in research studies and are not approved by the U.S. Food and Drug Administration (FDA).

Official Title

Delivery of D2C7-IT and 2141-V11 Combination Immunotherapy in Residual Disease for Adult Patients With Newly Diagnosed MGMT Unmethylated Glioblastoma and Perilymphatic Subcutaneous Injections of 2141-V11

Quick Facts

Study Start:2023-09-06

Study Completion:2028-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05734560

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 of age at the time of entry into the study 2. Newly diagnosed supratentorial glioblastoma, WHO grade 4, IDH wildtype, MGMT unmethylated (high grade glioma with molecular features of glioblastoma will be eligible under WHO 4 malignant glioma) with definitive resection prior to enrollment, with residual radiographic non-contrast enhancing disease on the post-operative CT or MRI of amenable to catheter placement. The residual radiographic contrast enhancing disease is ≤ 3 cm in maximal diameter in any plane. 3. Able to receive standard of care RT (typically 59.4-60 Gy over approximately 6 weeks duration if under 65 years old and a minimum of 40 Gy over 3 weeks duration if 65 years or older) 4. Karnofsky Performance Score (KPS) \> 70% 5. Hemoglobin ≥ 9 g/dl prior to catheter placement 6. Platelet count ≥ 100,000/µL unsupported. 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 7. Neutrophil count ≥ 1000 prior to catheter placement 8. Creatinine ≤ 1.5 x normal range prior to catheter placement 9. Total bilirubin ≤ 1.5 x ULN prior to catheter placement (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.) 10. AST/ALT ≤ 2.5 x ULN 11. 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 biopsy. 12. 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 13. A signed informed consent form approved by the Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study	1. Females who are pregnant 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 comorbidity, defined as follows: 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 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 5. Patients with uncontrolled diabetes mellitus 6. Patients with albumin allergy 7. Patients with known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects 8. Patients with known HIV or Hepatitis C positive status 9. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy 4. Patients who previously received other conventional therapeutic interventions for newly diagnosed glioblastoma with the exception of surgical resection for the brain tumor 5. Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of (actively growing) multifocal disease, tumor crossing the midline, extensive subependymal disease, or leptomeningeal disease 6. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the D2C7-IT infusion 7. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups) 8. 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 9. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months 10. 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 of age at the time of entry into the study
2. Newly diagnosed supratentorial glioblastoma, WHO grade 4, IDH wildtype, MGMT unmethylated (high grade glioma with molecular features of glioblastoma will be eligible under WHO 4 malignant glioma) with definitive resection prior to enrollment, with residual radiographic non-contrast enhancing disease on the post-operative CT or MRI of amenable to catheter placement. The residual radiographic contrast enhancing disease is ≤ 3 cm in maximal diameter in any plane.
3. Able to receive standard of care RT (typically 59.4-60 Gy over approximately 6 weeks duration if under 65 years old and a minimum of 40 Gy over 3 weeks duration if 65 years or older)
4. Karnofsky Performance Score (KPS) \> 70%
5. Hemoglobin ≥ 9 g/dl prior to catheter placement
6. Platelet count ≥ 100,000/µL unsupported. 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
7. Neutrophil count ≥ 1000 prior to catheter placement
8. Creatinine ≤ 1.5 x normal range prior to catheter placement
9. Total bilirubin ≤ 1.5 x ULN prior to catheter placement (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.)
10. AST/ALT ≤ 2.5 x ULN
11. 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 biopsy.
12. 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
13. A signed informed consent form approved by the Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study

1. Females who are pregnant 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 comorbidity, defined as follows:
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 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
5. Patients with uncontrolled diabetes mellitus
6. Patients with albumin allergy
7. Patients with known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
8. Patients with known HIV or Hepatitis C positive status
9. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy
4. Patients who previously received other conventional therapeutic interventions for newly diagnosed glioblastoma with the exception of surgical resection for the brain tumor
5. Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of (actively growing) multifocal disease, tumor crossing the midline, extensive subependymal disease, or leptomeningeal disease
6. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the D2C7-IT infusion
7. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
8. 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
9. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months
10. 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

Daniel Landi, MD

CONTACT

919-684-5301

dukebrain1@dm.duke.edu

Stevie Threatt

CONTACT

919-684-5301

dukebrain1@dm.duke.edu

Principal Investigator

Daniel Landi, MD

PRINCIPAL_INVESTIGATOR

Duke University

Study Locations (Sites)

Duke University Medical Center

Durham, North Carolina, 27710

United States

Collaborators and Investigators

Sponsor: Darell Bigner

Daniel Landi, 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 Date2023-09-06

Study Completion Date2028-02

Study Record Updates

Study Start Date2023-09-06

Study Completion Date2028-02

Terms related to this study

Keywords Provided by Researchers

D2C7
D2C7-IT
2141-V11
Pro00110119
GBM
Glioblastoma
convection-enhanced delivery
CED
MGMT unmethylated

Additional Relevant MeSH Terms

Newly Diagnosed MGMT Unmethylated Glioblastoma