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Rituximab and Hyaluronidase Human in Treating Patients with Unresectable Stage III-IV Melanoma Undergoing Nivolumab and Ipilimumab Therapy

Status
Active
Cancer Type
Melanoma
Trial Phase
Phase II
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT03719131
Protocol IDs
Winship4457-18 (primary)
NCI-2018-01804
IRB00105605
Study Sponsor
Emory University Hospital/Winship Cancer Institute

Summary

This phase II trial studies how well rituximab and hyaluronidase human works in treating patients with stage III-IV melanoma that cannot be removed by surgery (unresectable) who are undergoing nivolumab and ipilimumab therapy. Immunotherapy with rituximab and hyaluronidase human, may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread.

Objectives

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 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.

EXPLORATORY OBJECTIVE:
I. To compare treatment induced changes in tumor tissue in patients receiving CCB therapy + Rituxan versus CCB therapy alone.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive standard of care ipilimumab intravenously (IV) over 90 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes every 4 weeks for up to 13 doses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive standard of care ipilimumab and nivolumab as in Arm A. After 1 week, patients also receive rituximab and hyaluronidase human IV or subcutaneously (SC) weekly starting week 2 for 4 doses in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes every 4 weeks for up to 13 doses in the absence of disease progression or unacceptable toxicity.

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

Eligibility

  1. 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.
  2. Patients with progression on anti-PD-1 as a single agent are allowed to enroll on the study.
  3. No therapy with immune checkpoint inhibitors other than anti-PD-1 within 1 year prior to starting combination checkpoint therapy. Prior adjuvant ipilimumab as single agent is allowed if greater than 1 year since last treatment. Patient had no grade 3 or 4 toxicities from the checkpoint inhibitors including prior single agent PD-1 or anti CTLA4 therapy. History of adjuvant interferon is allowed.
  4. White blood count >= 3,000/uL (obtained within three weeks prior to randomization)
  5. Absolute neutrophil count (ANC) >= 1,500/uL (obtained within three weeks prior to randomization)
  6. Platelet count >= 100,000/uL (obtained within three weeks prior to randomization)
  7. Hemoglobin >= 9 g/dL (obtained within three weeks prior to randomization)
  8. Serum creatinine =< 1.5 x institutional upper limit of normal (ULN) or serum creatinine clearance (CrCl) >= 40 ml/min (obtained within three weeks prior to randomization)
  9. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (=< 5 x ULN for patients with documented liver metastases) (obtained within three weeks prior to randomization)
  10. Alkaline phosphatase =< 2 X ULN (=< 5 X ULN for those with bone metastasis) (obtained within three weeks prior to randomization)
  11. Total bilirubin =< 1.5 X ULN except those with direct bilirubin or Gilbert's syndrome (obtained within three weeks prior to randomization)
  12. Serum lactate dehydrogenase (LDH) =< 10 X ULN (obtained within three weeks prior to randomization)

Treatment Sites in Georgia

Winship Cancer Institute of Emory University


1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

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