| Eligibility |
Inclusion Criteria:
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.
- Prior 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
- Radiation:
- 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.
- Corticosteroids:
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.
Exclusion Criteria:
- 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 SIRPa 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.
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