Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Primary Central Nervous System Lymphoma

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

All Drugs and Chemicals

Methotrexate

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

HD-MTX containing induction chemotherapy (per standard of care) followed by Nivolumab consolidation.

Steven Park, MD

The primary objective of Stage 1 is to evaluate the safety of nivolumab consolidation after completion of HD-MTX containing induction chemotherapy in older subjects with PCNSL in terms of a tolerated dose (based on dose-limiting toxicities) for the expansion phase of the study (Stage 2).The primary objective of Stage 2 is to evaluate the efficacy of nivolumab consolidation after completion of HD-MTX containing induction chemotherapy in terms of the 2-year progression-free survival rate and compare to relevant historical controls

This is a 2-stage phase 1B study of nivolumab consolidation following completion of HD-MTX containing induction chemotherapy in older (≥ 65 years old) patients with previously untreated primary CNS lymphoma. Stage 1 is designed to evaluate the safety of nivolumab consolidation. We plan to use 3+3 design and start at the FDA approved single agent dose of nivolumab 480 mg intravenously every 4 weeks. Stage 2 is designed to evaluate the safety as well as efficacy of nivolumab consolidation after HD-MTX containing induction chemotherapy in an expansion cohort.

Nivolumab Consolidation in Older (≥ 65) Patients With Primary CNS Lymphoma

A Phase 1B Trial Nivolumab Consolidation Following Completion of High-Dose Methotrexate Containing Induction Chemotherapy in Older (≥ 65) Patients With Primary CNS Lymphoma

The primary endpoint for the Stage 1 phase of the study is dose-limiting toxicity which will be assessed for each Stage 1 subject using the DLT criteria

The primary endpoint for the Stage 1 phase of the study is the 2-year progression-free endpoint which will be determined for each subject as a binary variable indicating if they are alive and progression-free at 2 years (PFS2)

PFS is defined as the duration of time from enrollment to first occurrence of either progressive disease or death.

OS is defined as the duration from enrollment to the date of death from any cause.

Objective response will be determined for each subject as a binary variable indicating if they have achieved a best overall response of CR or PR as determined by the International Criteria for PCNSL (IPCG). Complete response will be determined for each subject as a binary variable indicating if they have achieved a best overall response of CR as determined by the International Criteria for PCNSL(IPCG).

Response conversion will be determined for each subject who achieve a best overall response of PR during induction therapy as a binary variable indicating if the subsequently achieve a best overall response of CR to nivolumab consolidation therapy.

Adverse events will be collected for each subject using NCI CTCAE v5.0 criteria. A binary variable will be determined for each subject indicating whether or not the subject experienced an AESI during treatment with nivolumab consolidation therapy, across any cycle nivolumab treatment administration.

A subset analysis of the primary population will be performed on those members of the evaluable population for the primary objective completing at least two cycles of nivolumab. PFS is defined as the duration of time from enrollment to first occurrence of either progressive disease or death.

Bristol-Myers Squibb

Atrium Health Levine Cancer Institute

Wake Forest University Health Sciences

Glioblastoma

Glioma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All patients will be participate in the intermittent, modified Atkins diet

Diet modification

Roy E. Strowd, MD

Jaishri O. Blakeley, MD

The primary goal of this study is to assess the feasibility and biologic activity of a modified Atkins-based diet combined with short-term intermittent fasting, a GLioma Atkins-based Diet (GLAD), in patients with central nervous system GBM.

Malignant gliomas have a high glycolytic rate and are dependent on glucose for energy metabolism. This so called "Warburg effect" or the reliance of central nervous system (CNS) tumor cells on glucose utilization through glycolysis has been identified as a potential therapeutic target in cancer metabolism. Preclinically, reduced cerebral glucose via calorie restriction has been repeatedly associated with tumor reduction and improved survival in glioma animal models. Such work has led to several early clinical studies evaluating the ketogenic diet (KD) in patients with recurrent GBM.

The modified Atkins diet (MAD) is designed to provide a more palatable, less restrictive but effective alternative to the strict KD, particularly for adults. The MAD does not require inpatient admission for initial fast, weight of foods, or severe dietary restrictions and is generally well tolerated, easier to administer, and more practical for adults. The MAD lacks calorie restriction, an important component to dietary therapies in preclinical investigations. Emerging evidence also suggests that short term fasting may provide superior anti-cancer activity to long term calorie restriction and that these benefits have been observed without substantial weight loss that can be observed with longer term calorie restriction.

In glioma patients, a diet therapy that combines the broad clinical application of the MAD with the caloric impact of short-term intermittent fasting is therefore optimal. Moreover, initiation of this diet when the cancer has already undergone induction therapy and is clinically and radiographically stable, may provide the optimal time for metabolic intervention to prevent recurrence or progression.

Glioma Modified Atkins-based Diet in Patients With Glioblastoma

The Feasibility and Biologic Effect of a Modified Atkins-based Intermittent Fasting Diet in Patients With Glioblastoma (GBM)

Percent of patients able to remain on the diet and achieve nutritional goals as defined by cumulative assessment of diet records collected at weeks 4, 6, and 8 with a 60% completion defined as a positive results

Measured by pre- and post-study cerebral glutamate and glutamine concentrations assessed by MRS.

Percent of patients who have an adverse reaction of any grade attributed to the diet of possible, probable, or definite

Dietary compliance will be assessed by serial changes in serum glucose, ketones, weight trajectory, body fat composition, change in seizure frequency without AED adjustment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab Consolidation in Older (≥ 65) Patients With Primary CNS Lymphoma	NCT04022980	Brain and Nervo... Eye and Orbit	Nivolumab	65 Years -	Wake Forest University Health Sciences
Nivolumab Consolidation in Older (≥ 65) Patients With Primary CNS Lymphoma	NCT04022980	Brain and Nervo... Eye and Orbit	Nivolumab	65 Years -	Wake Forest University Health Sciences
Glioma Modified Atkins-based Diet in Patients With Glioblastoma	NCT02286167	Glioblastoma Mu...	Diet modificati...	18 Years -	Wake Forest University Health Sciences
Glioma Modified Atkins-based Diet in Patients With Glioblastoma	NCT02286167	Glioblastoma Mu...	Diet modificati...	18 Years -	Wake Forest University Health Sciences
Glioma Modified Atkins-based Diet in Patients With Glioblastoma	NCT02286167	Glioblastoma Mu...	Diet modificati...	18 Years -	Wake Forest University Health Sciences

Spots Global Cancer Trial Database for central nervous system malignancy