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Lymphoma

Neoplasms by Histologic Type

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Lymphatic Diseases

Immunoproliferative Disorders

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Primary Central Nervous System Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Nivolumab administration Q2W by intraventricular injection through Ommaya reservoir

Jianmin Zhang, M.D.

The purpose of this study is to determine whether Nivolumab given intrathecally is effective in the treatment of Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL)

This is a case study aiming to recruit 1 patient. This study is indicated for relapsed/refractory primary central nervous system lymphoma. Primary objective is to explore the safety.

A Case Study of Nivolumab for Relapsed/Refractory Primary Central Nervous System Lymphoma

Adverse events Adverse events assessed according to NCI-CTCAE v5.0 criteria

Record individual best overall response(BOR), including CR, PR, SD, PD

Second Affiliated Hospital, School of Medicine, Zhejiang University

Hematologic Neoplasms

Hematologic Diseases

Amino Acids

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Part A1: Dose-level cohorts with up to approximately 6 patients each will be used to define the Maximum Tolerated Dose (MTD) for emavusertib.

Part A2: Evaluate escalating dose levels of oral emavusertib in combination with 560 mg daily (QD) of oral ibrutinib. The starting dose of emavusertib to be used in combination will be 200 mg twice a day (BID). It is anticipated that 12 to 20 patients at a potential dose level will be required to establish optimal combination dosing.

In two PCNSL Expansion Cohorts (Part B), emavusertib in combination with ibrutinib will be administered in patients with PCNSL. In Cohort 1, emavusertib 100 mg BID will be administered with ibrutinib 560 mg QD consecutively in a 28-day cycle in approximately 6 to 9 patients. In Cohort 2, CA-4948 200 mg BID will be administered with ibrutinib in at least 9 patients.

Emavusertib (formulated for oral administration for BID dosing)

Emavusertib

ibrutinib

Reinhard von Roemeling, MD

This is a multi-center, open-label trial to evaluate the safety, pharmacokinetics (PK), and anti-cancer activity of oral administration of emavusertib (CA-4948) in adult patients with relapsed or refractory (R/R) hematologic malignancies. Part A will evaluate the safety and tolerability of escalating doses of emavusertib as monotherapy (Part A1), and in combination with ibrutinib. In Protocol Version (v) 1.0 through v6.0, patients with Waldenström macroglobulinemia/ lymphoplasmacytic lymphoma (WM/LPL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) were also enrolled at ibrutinib doses of 420 mg (Part A2). Enrollment into Parts A1 and A2 has been closed. Part B will comprise 2 cohorts to assess safety and efficacy of emavusertib in combination with ibrutinib in patients with primary central nervous system lymphoma (PCNSL).

Part A will evaluate escalating doses of emavusertib (CA-4948) either as monotherapy (Part A1) or in combination with ibrutinib (Part A2). Enrollment is closed for Part A1 and A2. Part B will comprise two expansion cohorts to assess efficacy and safety of emavusertib and ibrutinib in PCNSL.

A Study of CA-4948 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma

An Open-Label, Dose Escalation and Dose Expansion Trial Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Orally Administered CA-4948 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma

The number of patients with a dose-limiting toxicity (DLT) in the first treatment cycle

MTD determined by the highest dose level studied at which fewer than 2 out of 6 subjects (\<33%) experience a dose limiting toxicity.

RP2D selected based on overall tolerability data from all patients treated at different dose levels and will not exceed the MTD.

Area Under the concentration-time curve (AUC)

Time to maximum plasma concentration (Tmax)

Plasma terminal elimination half-life (T 1/2)

CNS liquor with be sampled from an Ommaya reservoir or with a spinal puncture about 3 hours after oral dosing of emavusertib. At approximately the same timepoint, a peripheral blood sample will be taken to obtain a plasma sample. The respective emavusertib concentrations will be measured in the liquor and in plasma samples. The liquor vs plasma concentration ratio will provide a rough estimate of the blood-brain barrier (BBB) penetration of emavusertib following oral dosing.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Case Study of Nivolumab for Relapsed/Refractory Primary Central Nervous System Lymphoma	NCT04845139	Refractory Cent... Relapsed Primar... Primary Central...	Nivolumab	18 Years - 80 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
A Study of CA-4948 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma	NCT03328078	Relapsed Hemato... Refractory Hema... Relapsed Primar... Refractory Prim...	Emavusertib ibrutinib	18 Years -	Curis, Inc.
A Case Study of Nivolumab for Relapsed/Refractory Primary Central Nervous System Lymphoma	NCT04845139	Refractory Cent... Relapsed Primar... Primary Central...	Nivolumab	18 Years - 80 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
A Case Study of Nivolumab for Relapsed/Refractory Primary Central Nervous System Lymphoma	NCT04845139	Refractory Cent... Relapsed Primar... Primary Central...	Nivolumab	18 Years - 80 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University

Spots Global Cancer Trial Database for relapsed primary central nervous system lymphoma