IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Adult Glioblastoma

Launched by UNIVERSITY OF FLORIDA · Apr 25, 2022

Keywords

ClinConnect Summary

The IMPACT clinical trial is a research study exploring a new treatment for adult patients with glioblastoma, a type of aggressive brain tumor. This study is testing a special therapy called IL-8 receptor-modified CD70 CAR T cell therapy, which uses the patient's own immune cells to target and fight cancer cells. The main goal is to find out if this treatment is safe and feasible for patients with a specific type of glioblastoma that expresses a marker called CD70.

To participate in this trial, patients need to be at least 18 years old and have a newly diagnosed glioblastoma without a history of other brain tumors. Additionally, their tumor must show a certain level of CD70 positivity, and they should have had surgery to remove part of the tumor. Participants will go through a series of tests to ensure they meet the health criteria, such as having good blood counts and organ function. Throughout the study, participants will be closely monitored for their safety and response to the treatment. It's important for patients to understand that this is an early-stage trial, so the treatment is experimental, and they will need to provide informed consent to participate.

Gender

ALL

Eligibility criteria

• Inclusion Criteria (Adult GBM):
• • Age ≥ 18 years
• • Newly-diagnosed de novo GBM based on the absence of previous history of brain tumor (WHO Grade IV glioma) by histopathology or molecular studies. (secondary GBM not eligible)
• • The tumor must have a supratentorial component
• • CD70 positive (≥5%, 1+)
• Tumor expression will be scored on a scale of 0 to 3 staining intensity:
• • 0 = Negative
• • 1. = Low level
• • 2. = Moderate level
• • 3. = High level
• • The criteria for inclusion will be at least 5% of the cells scoring 1+ staining intensity (\> 5%, 1+).
• • Surgical resection of tumors with less than 3cm x 3cm (9 cm2) residual enhancing tumor as a product of longest perpendicular planes by MRI. (biopsy only subjects are not eligible for this study)
• • Karnofsky Performance Status (KPS) of \> 70%
• * CBC with differential with adequate bone marrow function as defined below:
• • Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
• • Platelet count ≥ 100,000 cells/mm3.
• • Hemoglobin ≥ 10 g/dl. (The use of transfusion or other intervention to achieve Hgb ≥ 10 g/dl is acceptable.)
• • Adequate renal function as defined below:
• • BUN ≤ 25 mg/dl
• • Creatinine ≤ 1.7 mg/dl
• • Adequate hepatic function as defined below:
• • Bilirubin ≤ 2.0 mg/dl
• • ALT ≤ 5 times institutional upper limits of normal for age
• • AST ≤ 5 times institutional upper limits of normal for age
• • Signed informed consent. If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the legally authorized representative.
• • For females of childbearing potential, a negative serum pregnancy test at enrollment.
• • Women of childbearing potential (WOCBP) must be willing to use an acceptable contraceptive method to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
• • Males with female partners of childbearing potential must agree to practice adequate contraceptive methods throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.
• Exclusion Criteria (Adult GBM):
• • Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3years. (In situ cancer are permissible)
• • Metastases detected below the tentorium or beyond the cranial vault
• • Leptomeningeal disease beyond the cranial vault. (Focal, adjacent and leptomeningeal involvement is allowable at the discretion of the PI).
• • Recurrent or multifocal malignant gliomas.
• • The patient is not a candidate for cellular therapy as assessed by the study bone marrow transplant physician.
• • Known immunosuppressive disease or human immunodeficiency virus (HIV) infection.
• • Rationale: The need to exclude patients with the immunosuppressive disease or human
• * Severe, active co-morbidity, defined as follows:
• • 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 initiation of XRT/TMZ.
• • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the initiation of XRT/TMZ.
• • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
• • Patients with an autoimmune disease requiring medical management with immunosuppressants.
• • 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 investigator's opinion, place the patient at high risk for radiation toxicity.
• • Pregnant or lactating women, due to possible adverse effects on the developing fetus or infant.
• • Patients treated on any other therapeutic clinical protocols within 30 days prior to enrollment.