Study of Concurrent Intravenous and Intrathecal Nivolumab for Patients With Leptomeningeal Disease (LMD)

• Status: Not yet recruiting
• Trial end date: 0000-00-00
• Target enrollment: 30
• Participant gender: All

Summary

This clinical research study consists of 2 phases: dose escalation (Phase 1) and dose expansion (Phase 2).

The goal of Phase 1 of this research study is to find the highest tolerable dose level of nivolumab that can be given both by intravenous (IV) infusion and intrathecal (IT) injection to patients with leptomeningeal disease (LMD). IV infusions are given by vein, while IT injections are given directly into the cerebrospinal fluid (CSF).

The goal of Phase 2 of this research study is to learn if the highest tolerable dose level combination found during Phase 1 can help to control the disease.

The safety of the drug combination will also be studied in both phases.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Bristol-Myers Squibb
• Treatments: Antibodies, Monoclonal; Nivolumab
• Last Updated: 2017-01-18

Criteria

Inclusion Criteria:

1. Patients must have radiographic and/or CSF cytological evidence of LMD.

2. Must have a confirmed diagnosis of metastatic melanoma (cutaneous, acral-lentiginous, uveal and mucosal in origin), based on histological analysis of metastatic tissue and/or cancer cells, archival tissue permitted.

3. Patients must have an ECOG PS of

4. Patients may receive steroids to control symptoms related to CNS involvement, but the dose must besymptoms should experience stability of neurological symptoms for at least 7 days, or on tapering dose of steroids. Physiologic replacement doses for adrenal insufficiency is allowed on this protocol.

5. Patients who have received radiation to brain and/or spine, including whole brain radiation, stereotactic radiosurgery, or SBRT, are eligible, but must have completed radiation treatment at least 7 days prior to the start of treatment.

6. Concurrent treatment with other anti-cancer systemic therapies is not allowed. No other concomitant intrathecal therapy with another agent will be allowed. For patients that have received other systemic therapies, the minimum wash out period is as follows:

• Patients that received previous IT therapy must have received their last treatment >/= 14 days prior to the start of treatment

• Patients who have received systemic chemotherapy must have received their last treatment >/= 21 days prior to the start of treatment

• Patients who have received an approved biologic therapy (e.g. anti-PD-1, anti-CTLA4, IL2, interferon) must have received their last treatment>/= 4 weeks prior to the start of treatment

7. contd from #7:

• Patients who have been treated with an approved targeted therapy (BRAF inhibitor and/or MEK inhibitor) must have received their last treatment >/= 28 days or 5 half-lives (whichever is shorter) prior to the start of treatment

• Patients who have received any other investigational agents must have received their last treatment >/= 28 days or 5 half-lives (whichever is shorter) prior to the start of treatment

8. Age >/= 18 years

9. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

10. Patients must have organ and marrow function: Hematologic: Absolute neutrophil count (ANC) >/= 1.5 X 10^9/L; Hemoglobin >/= 9.0 g/dL; Platelets >/= 75 X 10^9/L; PT/INR and PTT>1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%); AST and ALT;/= 2.5 g/dL; Renal: Creatinine ORCalculated creatinine clearance OR >/= 50 mL/min; 24-hour urine creatinine clearance >/= 50 mL/min.

Exclusion Criteria:

1. Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

2. Subjects with a condition requiring systemic treatment with either corticosteroids (> 4 mg daily dexamethasone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

3. Patients who have previously received a-PD-1 and/or anti-CTLA-4 will be eligible, unless they have ongoing >Grade 2 AE side effects of such therapy. Ongoing physiologic replacement doses for adrenal and thyroid insufficiency are allowed on protocol.

4. Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug

5. Pregnant or lactating female

6. Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled.

7. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection

8. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) even if fully immunocompetent on ART—due to the unknown effects of HIV on the immune response to combined nivolumab plus ipilimumab or the unique toxicity spectrum of these drugs in patients with HIV.

9. History of allergy to study drug components.

10. History of severe hypersensitivity reaction to any monoclonal antibody.

11. Prisoners or subjects who are involuntarily incarcerated.

12. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.