A study of a new anti-CD47 antibody therapy with an approved therapy rituximab or Rituximab + Chemotherapy in patients with a cancer of B-cells, a type of white blood cell responsible for producing antibodies, which has returned after a period of improvement or that has proved resistant, or does not respond to, treatment

Phase 1

• Conditions: Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma.; MedDRA version: 21.0Level: PTClassification code 10012821Term: Diffuse large B-cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: PTClassification code 10029624Term: Non-Hodgkin's lymphoma unspecified histology indolent stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: PTClassification code 10029601Term: Non-Hodgkin's lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: PTClassification code 10029600Term: Non-Hodgkin's lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10012822Term: Diffuse large B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: PTClassification code 10029623Term: Non-Hodgkin's lymphoma unspecified histology indolent stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: PTClassification code 10029622Term: Non-Hodgkin's lymphoma unspecified histology indolent stage ISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: PTClassification code 10065856Term: Non-Hodgkin's lymphoma unspecified histology indolentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-003408-29-GB
• Lead Sponsor: Gilead Sciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-01-11
• Last Update Posted: 5 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

1. Adults = 18 years
2. Antibody combination (magrolimab + rituximab) Phase 1b cohort only: B-cell NHL expressing CD20 by immunohistochemistry (IHC) or flow cytometry, relapsed or refractory to at least 2 prior lines of therapy
3. DLBCL chemotherapy combination (magrolimab + R-GemOx) Phase 1b safety dose-escalation and expansion cohorts:
a. Histologically confirmed de novo or transformed DLBCL relapsed or refractory to 1 to 3 prior lines of therapy who are not candidates for high dose chemotherapy and autologous stem cell transplantation (ASCT). Patients relapsed after ASCT are allowed.
b. At least 1 prior therapy must have included a CD20-targeted therapy.
c. Primary refractory patients are excluded as defined by failure to achieve a
partial response (PR) or complete response (CR) to frontline therapy or progression within 3 months of completing treatment.
d. The 1 to 3 prior lines of therapy requirement is only applicable for treatment regimens for DLBCL and not for prior lymphomas in the case of transformed DLBCL.
4. For the DLBCL antibody combination (magrolimab + rituximab) Phase 2 cohort 4: De novo or transformed DLBCL, not otherwise specified according to the World Health Organization 2016 classification of lymphoid neoplasms (Swerdlow 2016) expressing CD20 by IHC or flow cytometry that is relapsed or refractory at least 2 prior lines of therapy containing and anti-CD20 therapy. Prior autologous hematopoietic cell transplantation is permitted.
5. Indolent lymphoma Phase 2 Cohort: Histologically confirmed marginal zone
or follicular lymphoma (Grade 1 to 3a) expressing CD20 by IHC or flow cytometry, relapsed or refractory to at least 2 prior lines of therapy
6. Eastern Cooperative Oncology Group (ECOG) score 0 to 2
7. Disease that is measurable or assessable for response per Lugano Classification for lymphomas (Cheson 2014; Table 10-1)
8. Laboratory measurements, blood counts:
• Hemoglobin = 9.5 g/dL
• Absolute neutrophil count (ANC) = 1.0 × 109/mL
• For the antibody combination (magrolimab + rituximab) Phase 1b and Phase 2 cohorts: Platelets = 50 × 109/mL
• For the Phase 1b chemotherapy combination (magrolimab + R-GemOx)
safety dose-escalation and expansion cohorts only, platelets = 100 × 109/mL
9. Laboratory measurements, hepatic function:
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 5 × upper limit of normal (ULN)
• Bilirubin = 1.5 × or 3.0 × ULN and primarily unconjugated if patient has a documented history of Gilbert’s syndrome or a genetic equivalent
10. Laboratory measurements, renal function:
• Serum creatinine = 1.5 × ULN or calculated glomerular filtration rate (GFR) > 40 mL/min/1.73 m2
11. Women of childbearing potential (WOCBP) must not be nursing or planning to be pregnant and must have a negative urine or serum pregnancy test within 30 days before enrollment and within 72 hours before the first administration magrolimab.
12. WOCBP must be willing to use at least 1 highly effective method of contraception during the study and continue for 4 months after the last dose of magrolimab and 12 months after the last dose of rituximab
13. Male patients who are sexually active with a WOCBP and who have not had vasectomies must be willing to use a barrier method of contraception during and refrain from sperm donation during the study and for 4 months after the last dose of magrolimab and 12 months after the last dose of rituximab. If the partner is pregnant, male patients must

Exclusion Criteria

1. Patients with active brain metastases. (Patients with stable treated central nervous system [CNS] lesions who are off corticosteroid therapy for at least 3 weeks are not considered active.)
2. Prior allogeneic stem cell transplant
3. Prior anti-cancer therapy including chemotherapy, hormonal therapy, and investigational agents within 3 weeks or within at least 4 half-lives prior to magrolimab dosing (up to a maximum of 4 weeks), whichever is longer. NOTE: Low dose steroids (oral prednisone or equivalent = 20 mg per day), localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormone-releasing hormone (LHRH) agonists for prostate cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors are not criteria for exclusion.
4. Known active or chronic hepatitis B or C infection or human immunodeficiency virus (HIV).
5. Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of RBC transfusions during the 4-week period prior to screening. RBC transfusions are permitted during screening and prior to enrollment to meet the hemoglobin inclusion criteria.
6. History of hemolytic anemia or Evans syndrome in the last 3 months.
7. Positive IgG component of the direct antiglobulin test (DAT).
8. Prior treatment with CD47 or signal regulatory protein alpha (SIRPa)-targeting agents.
9. Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancy for which patients are not on active anti-cancer therapy as defined in Exclusion Criterion 2.
10. Hypersensitivity to the active substance, to murine proteins, or to any of the other excipients of rituximab listed in Appendix A.
11. Significant medical diseases or 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, severely immunocompromised state, and congestive heart failure New York Heart Association (NYHA) Class II-IV.
12. History of psychiatric illness or substance abuse likely to interfere with ability to comply with protocol requirements or give informed consent.
13. Pregnancy or active breastfeeding.
14. Additional exclusion criteria for DLBCL chemotherapy combination (magrolimab + R-GemOx) Phase 1b safety dose-escalation and expansion cohorts only:
a. Undergone ASCT within a period of = 3 months before signing informed consent.
b. Prior treatment with gemcitabine and oxaliplatin. However, patients who relapse = 12 months after treatment with a gemcitabine andoxaliplatin containing regimen are allowed.
c. Known hypersensitivity to gemcitabine, oxaliplatin, or other platinum compounds.
d. Intolerance of gemcitabine, oxaliplatin, and/or rituximab as monotherapy or in combination due to unacceptable toxicities as determined by the treating Investigator.

Study & Design

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