Rituximab and Hyaluronidase Human in Patients With Advanced Melanoma Undergoing Nivolumab and Ipilimumab Therapy

  • STATUS
    Recruiting
  • End date
    Oct 31, 2024
  • participants needed
    44
  • sponsor
    Emory University
Updated on 10 July 2022
platelet count
metastatic melanoma
absolute neutrophil count
monoclonal antibodies
direct bilirubin
metastasis
neutrophil count
liver metastasis
tumor cells
monoclonal antibody therapy
nivolumab
ipilimumab
blood count
immunomodulators
advanced melanoma
rituxan hycela
rituximab and hyaluronidase human

Summary

This phase II trial studies whether rituximab and hyaluronidase human (Rituxan Hycela) can prevent immune related adverse events in participants with stage III-IV melanoma that cannot be removed by surgery who are undergoing nivolumab and ipilimumab therapy.

Description

PRIMARY OBJECTIVE:

I. To compare rates for grade 3-4 immune-related adverse event (IRAE)s in the first 6 months in patients treated with combination checkpoint blockade (CCB) therapy (anti-CTLA4 and anti-PD1) as a part of standard of care for advanced melanoma who are treated with a single course of 4 weekly doses of rituximab and hyaluronidase human (Rituxan) therapy versus those who are not treated with Rituxan.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability (in terms of Rituxan-related adverse events) in patients with melanoma receiving CCB.

II. To compare objective response rate in patients receiving CCB therapy + Rituxan versus CCB therapy alone.

III. To compare 1 year overall and progression-free survival in patients receiving CCB therapy + Rituxan versus CCB therapy alone.

IV. To compare changes in cluster of differentiation 21lo (CD21lo) B cells in patients receiving CCB therapy + Rituxan versus CCB therapy alone.

V. To compare changes in T cells in patients receiving CCB therapy + Rituxan versus CCB therapy alone.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM A: Participants receive standard of care ipilimumab and nivolumab therapy.

ARM B: Participants receive standard of care ipilimumab and nivolumab therapy. On day 2 of each cycle, participants also receive rituximab and hyaluronidase human intravenously (IV) or subcutaneously (SC) weekly starting week 1 for 4 doses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up for 4 weeks.

Details
Condition Cutaneous Melanoma, Stage III, Cutaneous Melanoma, Stage IV, Stage III Melanoma, Stage IIIA Skin Melanoma, Stage IIIB Skin Melanoma, Stage IIIC Skin Melanoma, Stage IV Skin Melanoma, Unresectable Melanoma
Treatment Ipilimumab, Nivolumab, Rituximab and Hyaluronidase Human
Clinical Study IdentifierNCT03719131
SponsorEmory University
Last Modified on10 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Clinically eligible to receive Food and Drug Administration (FDA) approved standard of care combination immune checkpoint therapy with ipilimumab and nivolumab for unresectable stage III or stage IV melanoma
No therapy with immune checkpoint inhibitors within 1 year prior to starting combination checkpoint therapy. Prior adjuvant ipilimumab, nivolumab, or pembrolizumab as single agent is allowed if greater than 1 year since last treatment and patient had no grade 3 or 4 toxicities from the checkpoint inhibitors. History of adjuvant interferon is allowed
Obtained within one week prior to randomization
White blood count ≥ 3,000/µL
Absolute neutrophil count (ANC) ≥ 1,500/µL
Platelet count ≥ 100,000/µL
Hemoglobin ≥ 9 g/dL
Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) or serum creatinine clearance (CrCl) ≥ 40 ml/min
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (≤ 5 x ULN for patients with documented liver metastases)
Alkaline phosphatase ≤ 2 X ULN (≤ 5 X ULN for those with bone metastasis)
Total bilirubin ≤ 1.5 X ULN except those with direct bilirubin or Gilbert's syndrome
Serum lactate dehydrogenase (LDH) ≤ 10 X ULN

Exclusion Criteria

Allergy to rituximab, or any of the ingredients in rituximab injection or rituximab and hyaluronidase human injection
Patients with active central nervous system (CNS) metastatic disease or leptomeningeal disease. Patients with CNS metastatic disease that has been treated with surgical resection or stereotactic radiosurgery are eligible if lesions are stable for at least 4 weeks following therapy as determined by magnetic resonance imaging (MRI) scan done within one week of randomization
Prior therapy with immune checkpoint blocking antibodies (unless monotherapy given at least 1 year prior to starting combination therapy and no grade 3-4 toxicities while on monotherapy), vaccines or interleukin-2 (IL-2)
Patients may have had prior systemic therapy in the adjuvant setting (e.g. interferon, proto-oncogene B-Raf [BRAF], or mitogen-activated protein-extracellular signal-regulated kinase [MEK] agents). Adjuvant ipilimumab, nivolumab, or pembrolizumab as single agent is allowed if greater than 1 year since last treatment and patient had no grade 3 or 4 toxicities from the checkpoint inhibitors
Women must not be pregnant or lactating. Must have negative urine or blood pregnancy test within 1 week of starting therapy
Patients with known human immunodeficiency virus (HIV) are ineligible
Patients with active Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) are ineligible. -- ----Patients with prior history of, or serology suggestive of prior infection with Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) are also ineligible
Patients with active, known or suspected autoimmune disorders including lupus and type I diabetes are ineligible. Patients with history of vitiligo, thyroiditis are eligible
Patients with active disease or history of inflammatory bowel disease are ineligible
Patients cannot be on corticosteroid therapy except as physiologic replacement therapy
Patients receiving ongoing corticosteroid therapy for autoimmune disorders are ineligible. Occasional steroid inhaler use or nasal spray are allowed. Patients receiving replacement doses of steroids for adrenal insufficiency are eligible
Patients must not have any serious underlying medical conditions or take medications that in the investigators opinion may interfere with compliance or interpretation of Immune-related adverse events (IRAEs)
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