Nivolumab and Pomalidomide in Treating Patients With Relapsed or Refractory Central Nervous System Diffuse Large B Cell Lymphoma or Primary Vitreoretinal Diffuse Large B Cell Lymphoma

NCT03798314 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: MC178ANCI-2018-03661
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trials studies side effects and best dose of pomalidomide when given together with nivolumab in treating patients with primary central nervous system diffuse large B cell lymphoma or primary vitreoretinal diffuse large B cell lymphoma that has come back or that has not responded to treatment. Immunotherapy with monoclonal antibodies, such as pomalidomide and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Recurrent Nervous System Lymphoma; Recurrent Primary Vitreoretinal DLBCL; Refractory Nervous System Lymphoma; Refractory Primary Vitreoretinal DLBCL

Outcome Measures

Primary Outcomes (3)

• Maximum-tolerated dose (MTD) of pomalidomide

  The MTD in this study will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).

  Up to 28 days

• Incidence of adverse events

  Will be evaluated by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number and severity of all adverse events will be tabulated and summarized in this patient population both overall and by dose level. The grade 3+ adverse events will also be described and summarized in a similar fashion.

  Up to 12 weeks following end of treatment.

• Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment

  The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

  Up to 12 weeks following end of treatment

Secondary Outcomes (3)

• Overall response rate (ORR)

  Up to 4 years

• Progression-free survival (PFS)

  From registration to progression or death due to primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL), assessed up to 4 years

• Incidence of adverse events

  Up to 12 weeks following treatment

Study Arms (1)

Treatment (nivolumab and pomalidomide)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on day 1 and pomalidomide PO on days 1-14. Treatment repeats every 4 weeks until disease progression or unacceptable toxicity.

Biological: Nivolumab; Drug: Pomalidomide

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (nivolumab and pomalidomide)

Pomalidomide DRUG

Given PO

Also known as: 4-Aminothalidomide, Actimid, CC-4047, Imnovid, Pomalyst

Treatment (nivolumab and pomalidomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have one of the following:
• Relapsed or refractory primary central nervous system (CNS) diffuse large B cell lymphoma (PCNSDLBCL) with a brain lesion \>= 1 cm, or with cerebrospinal fluid (CSF) relapse with positive CSF cytology, or with ocular relapse with positive ocular tissue biopsy
• NOTE: Tissue biopsy is not absolutely necessary for brain tumor unless clinical and radiologic findings strongly suggest other etiologies as per treating physician. Initial diagnosis must be made by tissue biopsy OR
• Relapsed/refractory primary vitreoretinal diffuse large B cell lymphoma (DLBCL) with a CNS lesion \>= 1 cm, or with CSF relapse with positive CSF cytology, or with ocular relapse with positive ocular tissue biopsy. Relapsed PVRL must have progressed or failed at least one systemic regimen
• NOTE: Intraocular treatments are not regarded as systemic therapy
• NOTE: If recurrence in ocular or leptomeningeal space, the patient will need a positive ocular tissue biopsy and CSF biopsy. Tissue biopsy requirement of the CNS lesion is as outlined in bullet above
• Patient progressed after or did not respond to at least 1 line of systemic therapy (e.g., high-dose methotrexate, high-dose methotrexate based regimen, high dose cytarabine, etc)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 or 3
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within =\< 14 days prior to registration)
• Platelet count \>= 100,000/mm\^3 (within =\< 14 days prior to registration)
• Hemoglobin \>= 9.0 g/dL (within =\< 14 days prior to registration)
• Direct bilirubin \< 1.5 x upper limit of normal (ULN) (or total bilirubin =\< 3.0 x ULN with direct bilirubin =\< 1.5 x ULN in patients with well-documented Gilbert?s Syndrome) (within =\< 14 days prior to registration)
• Aspartate transaminase (AST) =\< 3 x ULN (within =\< 14 days prior to registration)
• Creatinine =\< 1.5 x ULN OR calculated creatinine clearance must be \>= 45 ml/min using the Cockcroft-Gault formula (within =\< 14 days prior to registration)
• Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =\< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of anticoagulants (within =\< 14 days prior to registration)

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration \[FDA\]-approved indication and in the context of a research investigation)
• Other active malignancy =\< 3 years prior to registration
• EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
• NOTE: If there is a history of prior malignancy, they must not have received immune checkpoint inhibitors or immunomodulatory therapy (IMiD) for their cancer
• History of myocardial infarction =\< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
• Use of corticosteroid in the absence of cerebral edema
• NOTE: If a corticosteroid is used, it should be used at the lowest dose possible for the shortest possible duration. Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of treatment assignment are excluded

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Nivolumab; pomalidomide

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Han Tun

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2019
• First Posted: January 9, 2019
• Study Start: January 30, 2019
• Primary Completion: December 30, 2020
• Study Completion: September 15, 2021
• Last Updated: January 6, 2023

Record last verified: 2021-09

Locations

US (2)