Brain Cancer Clinical Trial
Official title:
A Phase 1 Study of Magrolimab in Children and Adults With Recurrent or Progressive Malignant Brain Tumors
Children and adults with recurrent or progressive malignant brain tumors have a dismal prognosis, and outcomes remain very poor. Magrolimab is a first-in-class anticancer therapeutic agent targeting the Cluster of differentiation 47 (CD47)-signal receptor protein-alpha (SIRP-alpha) axis. Binding of magrolimab to human CD47 on target malignant cells blocks the "don't eat me" signal to macrophages and enhances tumor cell phagocytosis. Pre-clinical studies have shown that treatment with magrolimab leads to prolonged survival in models of Atypical Teratoid Rhabdoid Tumors (ATRT), diffuse intrinsic pontine glioma (DIPG), high-grade glioma (adult and pediatric), medulloblastoma, and embryonal tumors formerly called Primitive Neuro-Ectodermal Tumors (PNET). Safety studies in humans have proven that magrolimab has an excellent safety profile. Ongoing studies are currently testing magrolimab in adult myelodysplastic syndromes, acute myeloid leukemia, non-Hodgkin lymphoma, colorectal, ovarian, and bladder cancers. Herein we propose to test the safety of magrolimab in children and adults with recurrent or progressive malignant brain tumors.
This is a single arm, 2 strata multi-center study that will be conducted through the Pacific Pediatric Neuro-oncology Consortium (PNOC). Stratum A consists of children (ages 3-17) with recurrent or progressive malignant brain tumors and Stratum B consists of adults (ages ≥ 18) with recurrent or progressive malignant brain tumors. Participants with midline tumors (e.g., midline high grade gliomas (HGG), DIPG, and diffuse midline glioma) will be excluded. PRIMARY OBJECTIVES: Children (3-17 years of age) 1. To assess the safety and tolerability of magrolimab in children (Stratum A) with recurrent or progressive malignant brain tumors. 2. To determine the recommended Phase 2 dose (RP2D) for magrolimab in children (Stratum A) with recurrent or progressive malignant brain tumors. Adults (18 years and older) 1. To assess the safety and tolerability of magrolimab in adults (Stratum B) with recurrent or progressive malignant brain tumors. 2. To determine the recommended Phase 2 dose for magrolimab in adults (Stratum B) with recurrent or progressive malignant brain tumors. EXPLORATORY OBJECTIVES: 1. To evaluate the pharmacokinetic (PK) profile of magrolimab in blood and cerebrospinal fluid (CSF) in children and adults with recurrent or progressive malignant brain tumors. 2. To evaluate Ferumoxytol MRI imaging as a biomarker for intratumoral macrophages during treatment with magrolimab in children and adults with recurrent or progressive malignant brain tumors. 3. To evaluate the changes in the immune cells in the peripheral blood and CSF and changes in the immune cytokine milieu in the peripheral blood serum and CSF during treatment with magrolimab in children and adults with recurrent or progressive malignant brain tumors. 4. To evaluate the changes in the amounts of cell-free tumor DNA in the peripheral blood and CSF during treatment with magrolimab in children and adults with recurrent or progressive malignant brain tumors. 5. To assess Quality of Life (QOL) and cognitive measures in children and adults with recurrent or progressive malignant brain tumors treated on this trial. Participants may continue to receive magrolimab for up to 12 months or longer from the time of study entry, pending discussion with study chairs and study sponsor. Participants will be followed for up to 5 years after completion of treatment, or until removal from study, or until death, whichever occurs first. ;
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