Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma

Not Recruiting

Trial ID: NCT04892446

Purpose

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.

Official Title

A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma

Stanford Investigator(s)

Michaela Liedtke
Michaela Liedtke

Associate Professor of Medicine (Hematology)

Eligibility


Key Inclusion 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 Exclusion Criteria:

   - 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 (SIRPα)-targeting agents.

   - Current participation in another interventional clinical trial.

   - Autologous stem cell transplant < 100 days prior to enrollment.

   - Considered eligible to receive autologous or allogeneic stem cell transplant (SCT) at
   the time of enrollment.

   - Allogeneic SCT for the treatment of MM within 6 months of enrollment or active
   graft-versus-host disease requiring immunosuppression.

   - Significant neuropathy (Grade 3 to 4, or Grade 2 with pain) within 14 days prior to
   enrollment.

   - Known inherited or acquired bleeding disorders.

   - Known cirrhosis.

   - Clinical suspicion or documentation of central nervous system (CNS) disease.

   - 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 New York Heart Association (NYHA) Class III
   or IV heart failure.

   - Acute active infection requiring systemic antibiotics, antiviral (except antiviral
   therapy directed against reactivation) or antifungal agents within 14 days prior to
   enrollment.

   - 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.

   - Known active or chronic hepatitis B or C infection or human immunodeficiency virus
   (HIV) infection in medical history.

   - Active hepatitis B virus (HBV) and/or active hepatitis C virus (HCV), and/or HIV
   infection following testing at screening:

   - Individuals who test positive for hepatitis B surface antigen (HBsAg). Patients who
   test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by
   quantitative polymerase chain reaction (PCR) for confirmation of active disease.

   - Individuals who test positive for HCV antibody. Patients who test positive for HCV
   antibody will require HCV ribonucleic acid (RNA) by quantitative PCR for confirmation
   of active disease.

   - Individuals who test positive for HIV.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Intervention(s):

drug: Daratumumab

drug: Pomalidomide

drug: Dexamethasone

drug: Bortezomib

drug: Carfilzomib

drug: Magrolimab

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Michelle Gibson
650-723-0501

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