Magrolimab in Children and Adults With Recurrent or Progressive Malignant Brain Tumors (PNOC025)
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|ClinicalTrials.gov Identifier: NCT05169944|
Recruitment Status : Recruiting
First Posted : December 27, 2021
Last Update Posted : October 28, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Brain Cancer Malignant Brain Tumor Recurrent Brain Tumor Progressive Malignant Brain Tumor Brain Tumor, Pediatric Brain Tumor Adult||Drug: Magrolimab||Phase 1|
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.
Children (3-17 years of age)
- To assess the safety and tolerability of magrolimab in children (Stratum A) with recurrent or progressive malignant brain tumors.
- 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)
- To assess the safety and tolerability of magrolimab in adults (Stratum B) with recurrent or progressive malignant brain tumors.
- To determine the recommended Phase 2 dose for magrolimab in adults (Stratum B) with recurrent or progressive malignant brain tumors.
- 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.
- 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.
- 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.
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of Magrolimab in Children and Adults With Recurrent or Progressive Malignant Brain Tumors|
|Actual Study Start Date :||April 22, 2022|
|Estimated Primary Completion Date :||February 28, 2025|
|Estimated Study Completion Date :||February 28, 2025|
Experimental: Treatment (Magrolimab)
Each participant will receive magrolimab intravenously (IV) at a priming dose of 1 mg/kg during Cycle 0, followed by either 30 mg/kg or 45mg mg/kg dose weekly for eight weeks (Cycles 1 and 2), followed by either 30 mg/kg or 45 mg/kg dose every two weeks for the remainder of the study.
Anti-cancer therapeutic agent targeting the CD47-signal receptor protein-alpha (SIRP-alpha) axis
Other Name: Anti-CD47 Monoclonal Antibody
- Recommended Phase 2 Dose (RP2D) [ Time Frame: Up to 1 cycle (1 cycle is equal to 28 days) ]The investigator will employ the Bayesian optimal interval (BOIN) design to find the maximum tolerated dose (MTD). If the observed dose-limiting toxicity rate at the current dose is <= 0.236, the next cohort of patients will be treated at the next higher dose level; if it is >= 0.359, the next cohort of patients will be treated at the next lower dose level.
- Proportion of participants with treatment-emergent adverse events [ Time Frame: Up to 12 months ]The severity of toxicities will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events and will be summarized by maximum intensity and relationship to study drug.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||3 Years and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Study Participants in Stratum A and Stratum B:
- Diagnosis of recurrent or progressive malignant primary brain tumor (WHO grade III or IV), including recurrent ependymoma (WHO grade II and III).
- Histologic confirmation of malignancy at original diagnosis or relapse is required for study entry.
- Participants must have measureable disease. Measurable disease will be defined as lesions that can be accurately measured in two dimensions (longest diameters to be recorded) with a minimum size of no less than double the slice thickness. Previously irradiated lesions are considered non-measurable except in cases of documented progression of the lesion since the completion of radiation therapy.
- The patient must have failed at least one prior therapy, with or without surgery, prior to study registration. Prior therapies may include one of more of the following interventions: chemotherapy, immunotherapy, radiotherapy. Surgery alone does not constitute prior therapy. Patients must have fully recovered from clinically relevant acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Myelosuppressive chemotherapy: Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks prior if nitrosourea or mitomycin C.
- Biologic agent: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the biologic agent ≥ 7 days prior to study registration.
- For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended to beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
- For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the Study Chair prior to registration.
- Monoclonal antibody treatment: At least 28 days or 4 half-lives must have elapsed prior to registration, whichever is shorter. Such patients should be discussed with the study chair prior to registration.
Bone Marrow Transplant:
o Patients must be >= 3 months since autologous bone marrow/stem cell prior to registration
- Participants must have:
- Had their last fraction of local irradiation to primary tumor >=12 weeks prior to registration; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression.
- Had their last fraction of craniospinal irradiation or total body irradiation >+ 12 weeks prior to registration.
- Had their last fraction of palliative radiation ≥ 14 days prior to registration.
- Performance Score: Karnofsky >= 50 for participants > 16 years of age and Lansky >=50 for participants <=16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
o Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 7 days prior to enrollment. Stable dose should not be greater than dexamethasone 0.1 mg/kg/day (maximum 4 mg/day) or equivalent dose of alternate corticosteroid (physiologic replacement only).
Organ Function Requirements:
Adequate Bone Marrow Function Defined as:
- Peripheral absolute neutrophil count (ANC) 1000 mm3.
- Platelet count 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
- Hemoglobin>= 9.5 g/dL (RBC transfusions are permitted during the Screening Period and prior to enrollment to meet the hemoglobin inclusion criteria)
Adequate Renal Function Defined as:
- Creatinine clearance or radioisotope Glomerular filtration rate (GFR) >= 60 millilitre (mL) per minute (mL/min) 1.73 m2 or
- A serum creatinine based on age/gender as follows:
- Age: 2 to < 6 years, Maximum Serum Creatinine (mg/dL): Male 0.8, Female 0.8.
- Age: 6 to < 10 years, Maximum Serum Creatinine (mg/dL): Male 1.0, Female 1.0.
- Age: 10 to < 13 years, Maximum Serum Creatinine (mg/dL): Male 1.2, Female 1.2.
- Age: 13 to < 16 years, Maximum Serum Creatinine (mg/dL): Male 1.5, Female 1.4.
- Age: >= 16 years, Maximum Serum Creatinine (mg/dL): Male 1.7, Female 1.4.
- The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (CDC).
Adequate Liver Function Defined as:
- Bilirubin (sum of conjugated + unconjugated) <= 1.5 x upper limit of normal (ULN) for age, or 3.0 x ULN and primarily unconjugated if patient has a documented history of Gilbert's syndrome or genetic equivalent. Institutions whose total bilirubin ULN is < 1.2 mg/dL may adopt 1.2 mg/dL as their ULN.
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤ 2.5x ULN.
- Serum albumin ³ 2 g/dL.
Adequate Neurologic Function Defined as:
o Participants with seizure disorder may be enrolled if well controlled.
- The effects of magrolimab on the developing human fetus are unknown, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of magrolimab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.
- Participants who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 12 weeks prior to entering the study or those who have not recovered from clinically relevant acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Participants who are receiving any other investigational therapeutic agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to magrolimab, Ferumoxytol, or iron contained drugs or supplements.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infection.
- Women of childbearing potential must not be pregnant or breast-feeding.
- Participant has a known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- Participant has any prior positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., hepatitis B surface antigen ((HBsAg), Australia antigen) positive, or hepatitis C antibody (anti-HCV) positive, except if HCV-RNA negative.
- Prior treatment with CD47 or SIRPα targeting agents.
- Prior hemolytic anemia or Evans Syndrome in the last 3 months.
- RBC transfusion dependence, defined as requiring more than 2 units of RBCs transfused during the 4-week period prior to screening. RBC transfusions are permitted during the screening period and prior to enrollment to meet the hemoglobin inclusion criteria. Participants who require three or more units of RBCs during the 4-week period prior to enrollment.
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Participants with midline tumors, including midline HGG, DIPG, and diffuse midline glioma (DMG) or primary spinal cord tumors. Participants with disseminated disease are eligible.
- Participants at risk for imminent herniation, clinical evidence of significant increased intracranial pressure, or with >1 cm midline shift.
- Participants with a contraindication to MRI (metal implants).
- Participants with hemosiderosis/hemochromatosis, or iron overload from any cause (not just hemosiderosis or hemochromatosis), even if secondary to frequent blood transfusions, severe chronic hemolysis, excess dietary or parenteral iron, or any other etiology.
- Participants who have received a live vaccine within the last 30 days.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05169944
|Contact: Aubrie Drechsler||(415) 502-1600||PNOC025@ucsf.edu|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Jenna Weight 415-502-1600 PNOC025@ucsf.edu|
|Principal Investigator: Sabine Mueller, MD, PhD|
|United States, Utah|
|Huntsman Cancer Institute||Recruiting|
|Salt Lake City, Utah, United States, 84112|
|Contact: Howard Colman, MD, PhD 801-587-4024|
|University of Utah||Not yet recruiting|
|Salt Lake City, Utah, United States, 84113|
|Principal Investigator: Nicholas S Whipple, MD, MPH|
|Principal Investigator:||Sabine Mueller, MD, PhD||University of California, San Francisco|
|Study Chair:||Nicholas Whipple, MD, MPH||University of Utah|
|Study Chair:||Samuel Cheshier, MD, PhD||University of Utah|
|Study Chair:||Howard Colman, MD PhD FAAN||University of Utah|
|Study Chair:||Tab Cooney, MD||Dana-Farber/Boston Children's Cancer and Blood Disorders Center|
|Responsible Party:||Sabine Mueller, MD, PhD, Principal Investigator, University of California, San Francisco|
|Other Study ID Numbers:||
NCI-2021-13440 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
|First Posted:||December 27, 2021 Key Record Dates|
|Last Update Posted:||October 28, 2022|
|Last Verified:||October 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||Individual participant data after de-identification|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
CD47-signal receptor protein-alpha
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Central Nervous System Diseases
Nervous System Diseases
Antineoplastic Agents, Immunological