GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas(DIPG) & Spinal Diffuse Midline Glioma(DMG)
Trial ID or NCT#
NCT04196413
Status
RECRUITING
Purpose
The primary purpose of this study is to test whether GD2-CAR T cells can be successfully made from immune cells collected from children and young adults with H3K27M-mutant diffuse intrinsic pontine glioma (DIPG) or spinal H3K27M-mutant diffuse midline glioma (DMG). H3K27Mmutant testing will occur as part of standard of care prior to enrollment.
Official Title
Phase 1 Clinical Trial of Autologous GD2 Chimeric Antigen Receptor (CAR) T Cells (GD2CART) for Diffuse Intrinsic Pontine Gliomas (DIPG) and Spinal Diffuse Midline Glioma (DMG)
Eligibility Criteria
Ages Eligible for Study: 2 Years to 50 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Inclusion Criteria:
- - Currently accepting US patients only - Disease Status: - Tissue diagnosis of H3K27M-mutated Diffuse Intrinsic Pontine Glioma (DIPG) with radiographically evident tumor restricted to the brainstem, OR - Tissue diagnosis of H3K27M-mutated Diffuse Midline Glioma (DMG) of the spinal cord - Age: Greater than or equal to 2 year of age and less than or equal to 50 years of age Prior Therapy: - At least 6 weeks following completion of front line radiation therapy. - At least 3 weeks post chemotherapy or 5 half-lives, whichever is shorter must have elapsed since any prior systemic therapy, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives. - Performance Status: Subjects > 16 years of age: Karnofsky ≥ 60% OR Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Subjects ≤ 16 years of age: Lansky scale ≥ 60% - Normal Organ and Marrow Function (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion) 1. Absolute neutrophil count (ANC) ≥ 1,000/uL 2. Platelet count ≥ 100,000/uL 3. Absolute lymphocyte count ≥ 150/uL 4. Hemoglobin ≥ 8 g/dL 5. Adequate renal, hepatic, pulmonary and cardiac function defined as: - Creatinine within institutional norms for age (i.e. ≤ 2 mg/dL in adults or according to table below in children <18 years) OR creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min - Age (Years) -- Maximum Serum Creatinine (mg/dL) - ≤5 Years ---------------- 0.8mg/dL - 5 < age ≤ 10 Years ----1.0mg/dL - >10-18 Years -----------1.2mg/dL - >18 Years -----------2.0mg/dL - Serum Alanine aminotransferase( ALT)/Aspartate Aminotransferase (AST) ≤ 3.0 Upper limit of normal (ULN )(grade 1) - Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome. - Cardiac ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant ECG findings - Baseline oxygen saturation > 92% on room air - Pregnancy Test Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization are not considered to be of childbearing potential). - Contraception Subjects of child bearing or child fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative lymphodepletion regimen or for as long as GD2-CAR T cells are detectable in peripheral blood or cerebrospinal fluid (CSF). - Ability to give informed consent. Pediatric subjects will be included in age appropriate discussion and verbal assent will be obtained for those > 7 years of age, when appropriate.
Exclusion Criteria:
- - Tumor involvement of cerebellar vermis or hemispheres (pontocerebellar peduncle involvement is allowed), thalamic lesions, or supratentorial lesions. - Clinically significant swallowing dysfunction/dysphagia or prominent medullary dysfunction as judged by clinical assessment. - Current systemic corticosteroid therapy - Prior CAR therapy. - Prior GD2-antibody therapy - Ongoing use of dietary supplements, alternative therapies or extreme diets or any medication not approved by the investigators - Uncontrolled fungal, bacterial, viral, or other infection. Previously diagnosed infection for which the patient continues to receive antimicrobial therapy is permitted if responding to treatment and clinically stable. - Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti Hepatitis C Virus (HCV) positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chan reaction (PCR) and/or nucleic acid testing. - Clinically significant systemic illness or medical condition (e.g. significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement of the principal investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements. - In the investigator's judgment, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation. - Known sensitivity or allergy to any agents/reagents used in this study. - Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
Investigator(s)
Michelle Monje
Crystal Mackall
Paul Graham Fisher, MD
Neuro-oncologist,
Pediatric neurologist
Beirne Family Professor of Pediatric Neuro-Oncology, Professor of Pediatrics and, by courtesy, of Neurosurgery and of Epidemiology and Population Health
Lindsey Rasmussen
Timothy Thomas Cornell
Sneha Ramakrishna
Jasia Mahdi
Clinical Instructor, Neurology
Laura Prolo
Assistant Professor of Neurosurgery
Sonia Partap
Contact us to find out if this trial is right for you.
Contact
GD2CART@stanfordchildrens.org
650-497-7533
View on ClinicalTrials.gov
