A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma
Description
Brief Summary
The goal of this clinical study is to learn more about the safety and dosing of the study
drug, magrolimab, in combination with other anticancer therapies in participants with
relapsed/refractory multiple myeloma.
Phase
N/AInclusion and Exclusion Criteria
- All Individuals:
- Have been previously diagnosed with MM based on the IMWG 2016 criteria and currently requires treatment.
- Must have measurable disease as defined by 1 or more of the following:
- Serum monoclonal protein (M-protein) ≥ 0.5 grams per deciliter (g/dL) (greater than or equal to [≥] 5 grams per liter [g/L]).
- Urine M-protein ≥ 200 mg/24 hours (h).
- Serum free light chain (SFLC) assay: involved SFLC level ≥ 10 mg/dL (100 mg/L) with abnormal SFLC ratio.
- Has provided informed consent.
- Is willing and able to comply with clinic visits and procedure outlined in the study protocol.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Life expectancy ≥ 3 months.
- Absolute neutrophil count (ANC) ≥ 1000 cells/uL (1.0 x 10^9/L); granulocyte colony-stimulating factor (G-CSF) is not permitted within 1 week of screening to meet eligibility criteria.
- Platelet count ≥ 75,000 cells/uL (75 x 10^9/L); platelet transfusion is not permitted within 1 week of screening to meet eligibility criteria.
- Hemoglobin ≥ 9 g/dL; prior to initial dose of study treatment. Note: Transfusions are allowed to meet hemoglobin eligibility
- Adequate liver function as demonstrated by the following:
- Aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN).
- Alanine aminotransferase (ALT) ≤ 3.0 x ULN.
- Total bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN and primarily unconjugated if individual has a documented history of Gilbert's syndrome or genetic equivalent).
- International normalized ratio (INR) ≤ 1.2; Individuals receiving anticoagulation treatment may be allowed to participate if INR is within the therapeutic range prior to alternate assignment.
- Individuals must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min calculated by the Cockcroft-Gault formula or measured by 24 hours urine collection.
- Corrected serum calcium ≤ 2.9 millimoles per liter (mmol/L) (11.5 mg/dL); measures to reduce calcium to acceptable levels, such as a short course of steroids, bisphosphonates, hydration, or calcitonin are acceptable.
- Pretreatment blood cross-match completed.
- Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
- Must be willing to consent to mandatory pretreatment and on-treatment bone marrow biopsies (trephines).
- Magrolimab in Combination with Daratumumab: In addition to fulfilling the inclusion criteria for all individuals, individuals who are assigned to receive magrolimab in combination with daratumumab should fulfill the following:
- Must have received at least 3 previous lines of therapy for MM including an IMiD such as lenalidomide and a PI such as bortezomib.
- Individuals must have not had prior anti-CD38 antibody therapy for at least 6 months prior to enrollment.
- No prior history of discontinuation of daratumumab due to toxicity.
- Magrolimab in Combination with Pomalidomide and Dexamethasone: In addition to fulfilling the inclusion criteria for all Individuals, Individuals who are assigned to receive magrolimab in combination with pomalidomide and dexamethasone should fulfill the following:
- Must have received at least 3 previous lines of therapy for MM including an IMiD such as lenalidomide and a PI such as bortezomib.
- Prior treatment with pomalidomide is allowed if the Individual achieved at least a PR to the most recent pomalidomide therapy and will have had at least a 6-month treatment-free interval from the last dose of pomalidomide until first study treatment.
- No prior history of discontinuation of pomalidomide due to toxicity.
- No contraindication to dexamethasone.
- Magrolimab in Combination with Carfilzomib and Dexamethasone: In addition to fulfilling the inclusion criteria for all patients, patients who are assigned to receive magrolimab in combination with carfilzomib and dexamethasone should fulfill the following:
- Patient must have received at least 3 previous lines of therapy for MM including an IMiD such as lenalidomide and a PI such as bortezomib.
- Prior treatment with a PI, including carfilzomib, is allowed if the patient achieved at least a PR to the most recent prior PI therapy, and will have had at least a 6-month PI treatment-free interval from the last dose until first study treatment.
- No prior history of discontinuation of carfilzomib due to toxicity.
- No contraindication to dexamethasone
- Magrolimab in Combination with Bortezomib and Dexamethasone: In addition to fulfilling the inclusion criteria for all individuals, individuals who are assigned to receive magrolimab in combination with bortezomib and dexamethasone should fulfill the following:
- Must have received at least 1 previous line of therapy for MM including an IMiD such as lenalidomide and a PI such as bortezomib.
- Prior treatment with a PI, including bortezomib, is allowed if the Individual achieved at least a PR to the most recent prior PI therapy, and will have had at least a 6-month PI treatment-free interval from the last dose until first study treatment.
- No prior history of discontinuation of bortezomib due to toxicity.
- No contraindication to dexamethasone. Key
- Individuals with known amyloidosis including myeloma complicated by amyloidosis.
- Multiple myeloma of immunoglobulin M subtype.
- Individuals with Waldenstrom's macroglobulinemia.
- Individuals with myelodysplastic syndrome (MDS).
- Plasma cell leukemia (defined as either 20% of peripheral blood white blood cell (WBC) count comprised of plasma/CD138-positive cells) or circulating plasma cells ≥ 2 x 10^9/L.
- Individuals with solitary bone or extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
- Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS) syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes).
- Glucocorticoid therapy (prednisone > 40 mg/day or equivalent) within 14 days prior to enrollment; corticosteroid therapy for hypercalcemia is allowed.
- Chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to enrollment.
- Focal radiation therapy within 7 days prior to enrollment; radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to enrollment (ie, prior radiation must have been to less than 30% of the bone marrow).
- Immunotherapy within 28 days prior to enrollment.
- Major surgery (excluding procedures to stabilize the vertebrae) within 28 days prior to enrollment.
- Positive serum pregnancy test.
- Breastfeeding female.
- Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient.
- Prior treatment with CD47 or signal regulatory protein alpha (SIRP
Sites
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.
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