Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Lymphoma

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

All Drugs and Chemicals

Janus Kinase Inhibitors

Ruxolitinib

The Purpose of this trial is:

* to determine the overall response rate (ORR, complete response \[CR\] + partial response \[PR\]) in patients with relapsed or refractory HL
* to determine the safety profile of ruxolitinib in patients with relapsed or refractory HL

JAK-inhibition in Recurrent Classical Hodgkin Lymphoma

A Phase II, Open-label, Prospective, Non-randomized, Multicenter Clinical Trial With the JAK-inhibitor Ruxolitinib in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

University of Cologne

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Carcinoma, Renal Cell

Lung Neoplasms

Urinary Bladder Neoplasms

Melanoma, Cutaneous Malignant

Squamous Cell Carcinoma of Head and Neck

Skin Neoplasms

Neoplasms, Glandular and Epithelial

Disease Attributes

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neoplasms, Squamous Cell

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Kidney Neoplasms

Kidney Diseases

Head and Neck Neoplasms

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Nivolumab

Pembrolizumab

Antibodies

Immunoglobulins

Enzyme Inhibitors

Antibodies, Blocking

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive trigriluzole PO QOD, BID, QAM or QHS on days -14 to -1. Patients then receive nivolumab IV over 60 minutes every 2 weeks beginning week 1 and trigriluzole PO QOD, BID, QAM or QHS. Once the MTD of trigriluzole with nivolumab is identified, patients receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

Enzyme Inhibitor Therapy

Laboratory Biomarker Analysis

Biren Saraiya

This phase I trial studies the best dose and side effects of trigriluzole in combination with nivolumab and pembrolizumab in treating patients with solid malignancies or lymphoma that has spread to other places in the body or cannot be removed by surgery. Trigriluzole may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab and pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving trigriluzole in combination with nivolumab and pembrolizumab may work better at treating patients with solid malignancies or lymphoma.

PRIMARY OBJECTIVES:

I. The primary objective of this study is to determine the safety of trigriluzole in combination with PD-1 inhibiting antibodies, and to define a maximum tolerated dose (MTD) of trigriluzole in combination therapy.

SECONDARY OBJECTIVES:

I. To characterize the efficacy of the combination therapy. II. To identify markers of response to trigriluzole in the tumor microenvironment.

OUTLINE: This is a dose-escalation study of trigriluzole.

Patients receive trigriluzole orally (PO) every other day (QOD), twice daily (BID), every morning (QAM) or every bedtime (QHS) on days -14 to -1. Patients then receive nivolumab intravenously (IV) over 60 minutes every 2 weeks beginning week 1 and trigriluzole PO QOD, BID, QAM or QHS. Once the MTD of trigriluzole with nivolumab is identified, patients receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for up to 3 years.

Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma

A Phase I Study to Evaluate the Safety of Trigriluzole (FC-4157/BHV-4157) in Combination With PD-1 Blocking Antibodies

The MTD of trigriluzole in combination with nivolumab will be identified. The MTD will then be tested in combination with pembrolizumab using the same escalate/de-escalate/stay rules. Data on the adverse event type, severity and frequency will be recorded.

A DLT was any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0) that was possibly Trigriluzole or Nivolumab related. CTCAE 3.0 Grade 3 is a severe AE and Grade 4 is a life- threatening or disabling AE. DLTs were collected to determine the Maximum-Tolerated Dose (MTD), which is defined as the dose level below the dose at which 33% of participants experienced a DLT.

Continuous variables will be presented by summary statistics (such as mean, median, standard error and 95% confidence intervals \[CI\]) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 95% CI).

Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).

National Cancer Institute (NCI)

Rutgers, The State University of New Jersey

Assistant Professor, Medical Oncology

Cohort 1: Participants were administered 240 mg of Nivolumab every two weeks, via intravenous catheter (IV), for 2 weeks, and Trigriluzole 140 mg (PO), with one year of follow-up after the start of treatment.

Once the MTD of Trigriluzole with nivolumab is identified, participants receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and Trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

Experimental: Nivolumab 240mg IV Every 2 Weeks - Trigriluzole 140 mg Taken by Mouth Daily (PO)

Cohort 2: Participants were administered 240 mg of Nivolumab every two weeks, via intravenous catheter (IV), for 2 weeks, and Trigriluzole 140 mg (PO) Twice a day (BID), with one year of follow-up after the start of treatment.

Once the MTD of Trigriluzole with nivolumab is identified, participants receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and Trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

Experimental: Nivolumab 240mg IV Every 2 Weeks - Trigriluzole 140 mg PO Twice a Day (BID)

Cohort 3: Participants were administered 240 mg of Nivolumab every two weeks, via intravenous catheter (IV) and Trigriluzole 140 mg (PO) once a day in the morning (QAM) and 280mg PO every night at bedtime (QHS), with one year of follow-up after the start of treatment.

Once the MTD of Trigriluzole with nivolumab is identified, participants receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and Trigriluzole PO. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

Experimental: Nivolumab 240mg IV Every 2 Weeks - Trigriluzole 140 mg /280mg

Cohort 4: Participants were administered 240 mg of Nivolumab every two weeks, via intravenous catheter (IV) and Trigriluzole 140 mg (PO) once a day in the morning (QAM) and 280mg PO every night at bedtime (QHS), with one year of follow-up after the start of treatment.

Once the MTD of Trigriluzole with nivolumab is identified, participants receive pembrolizumab IV over 30 minutes every 3 weeks beginning week 1 and Trigriluzole 200mg PO BID. Treatment repeats for up to 1 year in the absence of disease progression or unacceptable toxicity.

Experimental: Nivolumab 240mg IV Every 2 Weeks - Trigriluzole 280mg PO BID

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Dr. Biren Saraiya - Associate Professor of Medicine Medical Director, Office of Human Research Servi

All participants who received at least 1 dose of Trigriluzole (140 mg or 280mg ) in combination with Nivolumab (240mg IV)

All Participants

Maximum Tolerated Dose (MTD))/Recommended Phase 2 Dose of Trigriluzole

Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)

Nivolumab 240mg IV Every 2 Weeks - Trigriluzole 280mg PO BID

Objective Response Rate Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
JAK-inhibition in Recurrent Classical Hodgkin Lymphoma	NCT02164500	Recurrent Class...	Ruxolitinib	18 Years - 99 Years	University of Cologne
Trigriluzole With Nivolumab and Pembrolizumab in Treating Patients With Metastatic or Unresectable Solid Malignancies or Lymphoma	NCT03229278	Lymphoma Metastatic Mali... Metastatic Mela... Metastatic Rena... Recurrent Bladd... Recurrent Class... Recurrent Head ... Recurrent Lymph... Recurrent Malig... Recurrent Renal... Stage III Bladd... Stage III Lymph... Stage III Non-S... Stage III Renal... Stage III Skin ... Stage IIIA Non-... Stage IIIA Skin... Stage IIIB Non-... Stage IIIB Skin... Stage IIIC Skin... Stage IV Bladde... Stage IV Lympho... Stage IV Non-Sm... Stage IV Renal ... Stage IV Skin M... Stage IVA Bladd... Stage IVB Bladd... Unresectable He... Unresectable So...	Enzyme Inhibito... Laboratory Biom... Nivolumab Pembrolizumab	18 Years -	Rutgers, The State University of New Jersey

Spots Global Cancer Trial Database for recurrent classical hodgkin lymphoma