A Study of Magrolimab Combinations in Patients with Relapsed/Refractory Multiple Myeloma

Phase 1

• Conditions: Relapsed/Refractory Multiple Myeloma; MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-001798-21-CZ
• Lead Sponsor: Gilead Sciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-11-16
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 153

Inclusion Criteria

1) Patient has been previously diagnosed with MM based on the International Myeloma Working Group (IMWG) 2016 criteria and currently requires treatment.
2) Patients must have measurable disease as defined by 1 or more of the following:
a) Serum monoclonal protein (M-protein) = 0.5 g/dL (= 5 g/L)
b) Urine M-protein = 200 mg/24 h
c) Serum free light chain (SFLC) assay: involved SFLC level = 10 mg/dL (100 mg/L) with abnormal SFLC ratio
3) Patient has provided informed consent.
4) Patient is willing and able to comply with clinic visits and procedure outlined in the study protocol.
5) Male or female = 18 years of age
6) Eastern Cooperative Oncology Group (ECOG) performance status = 2
7) Life expectancy = 3 months
8) Absolute neutrophil count (ANC) = 1000 cells/dL (1.0 x 109/L); granulocyte colony-stimulating factor (G-CSF) is not permitted within 1 week of screening to meet eligibility criteria.
9) Platelet count = 75,000 cells/dL (75 x 109/L); platelet transfusion is not permitted within 1 week of screening to meet eligibility criteria.
10) Hemoglobin = 9.0 g/dL; no more than 4 units of packed RBCs are allowed in the 30 days prior to screening
11) For patients with prior cardiac history such as ischemic heart disease, left ventricular ejection fraction = 45%, symptomatic congestive heart failure, New York Heart Association (NYHA) Class III or IV heart failure, or other conditions that may be sensitive to demand ischemia, the hemoglobin must be = 9.5 g/dL prior to initial dose of study treatment. Transfusions are allowed to meet hemoglobin eligibility criterion.
12) Adequate liver function as demonstrated by the following:
a) AST = 3.0 x upper limit of normal (ULN)
b) ALT = 3.0 x ULN
c) Total bilirubin = 1.5 x ULN (or = 3.0 x ULN and primarily unconjugated if patient has a documented history of Gilbert’s syndrome or genetic equivalent).
13) Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time = 1.2; patients receiving anticoagulation treatment may be allowed to participate if INR is within the therapeutic range prior to alternate assignment.
14) Patients 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.
15) Corrected serum calcium = 2.9 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.
16) Pretreatment blood cross-match completed (Section 7.8.1)
17) Male and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception
18) Patients must be willing to consent to mandatory pretreatment and on-treatment bone marrow biopsies (trephines).
Magrolimab in Combination Wwith Daratumumab
19) 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.
20) Patients must have CD38-positive myeloma and have not had prior anti-CD38 antibody therapy for at least 6 months prior to enrollment.
21) No prior history of discontinuation of daratumumab due to toxicity Magrolimab in Combination With Pomalidomide and Dexamethasone
22) 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.
23) Prior treatment with pomalidomide is allowed if the patient

Exclusion Criteria

1) Patients with known amyloidosis including myeloma complicated by amyloidosis
2) Multiple myeloma of immunoglobulin M subtype
3) Patients with Waldenstrom’s macroglobulinemia
4) Patients with MDS
5) 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 × 109/L
6) Patients with solitary bone or extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
7) POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes)
8) Glucocorticoid therapy (prednisone > 40 mg/day or equivalent) within 14 days prior to enrollment; corticosteroid therapy for hypercalcemia is allowed
9) Chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to enrollment
10) 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)
11) Immunotherapy within 28 days prior to enrollment
12) Major surgery (excluding procedures to stabilize the vertebrae) within 28 days prior to enrollment
13) Positive serum pregnancy test
14) Breastfeeding female
15) Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient
16) Prior treatment with CD47 or SIRPa-targeting agents.
17) Current participation in another interventional clinical trial
18) Autologous stem cell transplant < 100 days prior to enrollment
19) Considered eligible to receive autologous or allogeneic SCT at the time of enrollment
20) Allogeneic SCT for the treatment of MM within 6 months of enrollment or active graft-versus-host disease requiring immunosuppression
21) Significant neuropathy (Grade 3 to 4, or Grade 2 with pain) within 14 days prior to enrollment
22) Known inherited or acquired bleeding disorders
23) Known cirrhosis
24) Clinical suspicion or documentation of CNS disease
25) Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, congestive heart failure, or NYHA Class III or IV heart failure.
26) Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed against reactivation) or antifungal agents within 14 days prior to enrollment
27) Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which patients are not on active anticancer therapies and have had no evidence of active malignancy for at least 1 year. Other exceptions may be considered with sponsor approval. Previous hormonal therapy with luteinizing hormone-releasing hormone agonists for prostate cancer and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors are not criteria for exclusion.
28) Known active or chronic hepatitis B or C infection or HIV infection in medical history
29) Active hepatitis B virus (HBV) and/or active hepatitis C virus (HCV), and/or HIV infection following testing at screening:
a) Patients who test positive for hepatitis B

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified