Maintenance Obinutuzumab in Treating Patients With Central Nervous System Lymphoma Who Have Achieved a Complete or Partial Response

Primary Central Nervous System Lymphoma Clinical Trial

Official title:

Maintenance Obinutuzumab for Primary Central Nervous System Lymphoma Complete or Partial Responders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06175000
• Other study ID #: PHS-OB-PCNSL-01
• Status: Recruiting
• Phase: Phase 2
• Start date: March 13, 2024
• Est. completion date: September 15, 2029

Study information

• Verified date: March 2024
• Source: Providence Health & Services
• Contact: Tiffany Gervasi-Follmar
• Phone: 503-216-1023
• Email: tiffany.gervasi-follmar[@]providence.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies how well obinutuzumab works as maintenance treatment in patients with central nervous system lymphoma who have achieved the disappearance of all signs of cancer in response to treatment (complete response) or a decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment (partial response). Immunotherapy with obinutuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.

Description:

PRIMARY OBJECTIVE:

I. To determine the effect of maintenance obinutuzumab on duration of response (partial response [PR] or complete response [CR]) in patients with CD20+ B-cell primary central nervous system lymphoma (PCNSL) who attain PR or CR to first-line treatment with high-dose methotrexate-based chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate overall survival after PR or CR (overall survival [OS]-PRCR). II. To evaluate neurocognitive function, quality of life, and neuroimaging as indicators of neurotoxicity.

III. Progression-free survival (PFS) and overall survival (OS) will be calculated.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I (MAINTENANCE THERAPY): Patients receive obinutuzumab intravenously (IV) on days 1 and 2 for the first cycle, and on day 1 for the subsequent cycles. Cycles repeat every 60 days for 2 years in the absence of disease progression or unacceptable toxicity.

ARM II (OBSERVATION): Patients undergo observation for a total of 2 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 15, 2029
• Est. primary completion date: September 15, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• CD20+ B-cell primary central nervous system lymphoma (PCNSL) confirmed at the time of diagnosis by histology, cytology, or immunocytochemistry from cerebrospinal fluid (CSF); diagnosis must be documented by pathology report.

• Must have undergone first-line treatment with a high-dose methotrexate-based chemotherapy regimen with or without brain radiotherapy; high-dose methotrexate is defined as >= 3 grams/m^2; methotrexate dose reduction for creatinine clearance < 100 ml/min is permitted

• Must be within 75 days of completion of first-line treatment regimen; must have achieved objective response (PR or CR/unconfirmed complete response [CRu]) to first-line treatment

• Brain magnetic resonance imaging (MRI) documenting objective response must be obtained within 30 days of study enrollment

• If CSF was positive for lymphoma cells at diagnosis or during first-line treatment and/or a slit lamp examination was positive at diagnosis or during first-line treatment, then the CSF and vitreal studies must have been repeated and must have indicated CR; Note: CR requires complete disappearance of all enhancing abnormalities on gadolinium-enhanced MRI; if CSF was positive for lymphoma cells at diagnosis or during first-line treatment and/or slit lamp examination was positive at diagnosis or during first-line treatment, then the CSF and vitreal studies must have been repeated and must have indicated CR; for CRu, some patients will have a small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage; it is often difficult to ascertain whether this represents a residual nidus of tumor or scar tissue; if the abnormality does not change or slowly involutes without therapy and corticosteroids, it is reasonable to categorize as a CRu; at the time CR/CRu is determined, the patient should not have used corticosteroids for at least two weeks

• Karnofsky performance status (KPS) >= 60; Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2

• Signed informed consent form (ICF)

• Ability and willingness to comply with the requirements of the study protocol

• Total bilirubin < 3 x the upper limit of normal (ULN), +/- 7 days from date of ICF signing

• Creatinine clearance > 30 mL/min (calculated according to institutional standards or using Cockcroft-Gault formula), +/- 7 days from date of ICF signing

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 5 x ULN, +/- 7 days from date of ICF signing

• Platelet >= 75,000 cells/mm^3, +/- 7 days from date of ICF signing

• Hemoglobin > 9 g/dL, +/- 7 days from date of ICF signing

• Absolute neutrophil count > 1.5 x 10^3 cells/mm^3, +/- 7 days from date of ICF signing

• Surgically sterile or agree to use effective contraception using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly while receiving obinutuzumab and >= 18 months after the last dose of obinutuzumab for women, and 180 days after the last dose of obinutuzumab for men

Exclusion Criteria:

• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

• Clinical evidence of extra-central nervous system (CNS) (systemic) non-Hodgkin lymphoma

• Known hypersensitivity to any of the study drugs

• History of other malignancy that could affect compliance with the protocol or interpretation of results

• Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible; patients with a malignancy that has been treated, but not with curative intent, will also be excluded, unless the malignancy has been in remission without treatment for >= 2 years prior to enrollment

• Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks prior to study enrollment

• Major surgery within 4 weeks prior to study enrollment

• Known infection with human immunodeficiency virus (HIV)

• Known positive hepatitis serologies:

• Hepatitis B (HBV): patients with positive serology for hepatitis B defined as positivity for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (anti-HBc); patients who are positive for anti-HBc may be considered for inclusion in the study on a case-by-case basis if they are hepatitis B viral deoxyribonucleic acid (DNA) negative and are willing to undergo ongoing HBV DNA testing by real-time polymerase chain reaction (PCR); patients with positive serology may be referred to a hepatologist or gastroenterologist for appropriate monitoring and management

• Hepatitis C (HCV): patients with positive hepatitis C serology unless HCV ribonucleic acid (RNA) is confirmed negative and may be considered for inclusion in the study on a case-by-case basis

• Women who are pregnant or lactating

• Vaccination with a live vaccine a minimum of 4 weeks prior to study enrollment

Related Conditions & MeSH terms

• Lymphoma
• Primary Central Nervous System Lymphoma

Intervention

Procedure:
• Cognitive Assessment
Ancillary studies to evaluate neurocognitive function at study entry and at 2 years after study entry.

Biological:
• Obinutuzumab
Given IV

Other:
• Quality of Life Assessment
Ancillary studies to evaluate quality of life at study entry and at 2 years after study entry.

Locations

Country	Name	City	State
United States	Providence St. Vincent Medical Center	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Providence Health & Services

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Partial response (PR) or complete response (CR) duration	PR or CR duration will be assessed using Kaplan-Meier product limit estimates and compared between patients with maintenance versus without obinutuzumab maintenance using the log-rank test. In addition, the Cox proportional hazard model will be used to estimate hazard ratios.	From the date of brain magnetic resonance imaging (MRI) after completion of first-line treatment which confirms PR or CR, to disease progression or death, assessed up to 2 years
Secondary	Overall survival (OS) after CR	OS after PR or CR will be assessed using Kaplan-Meier product limit estimates and compared between patients with maintenance versus without obinutuzumab maintenance using the log-rank test. In addition, the Cox proportional hazard model will be used to estimate hazard ratios.	From the date of brain MRI after completion of first-line treatment which confirms PR or CR, to death, assessed up to 2 years
Secondary	Neurocognitive function - Wechsler Adult Intelligence Scale	Will be measured by the Wechsler Adult Intelligence Scale. Scale range 0 to 16 Forward; 0 to 14 Backward. Higher the score means better outcome. Longitudinal data of neurocognitive function will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.	Up to 2 years
Secondary	Quality of life (QOL) - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Brain Neoplasm 20-item	Will be measured by the European Organization for Research and Treatment of Cancer Quality of Life Brain Cancer Module-20 (EORTC QLQ-BN20) questionnaire. Scale 20 to 80 points. Higher score means worse outcome. Longitudinal data of QOL will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.	Up to 2 years
Secondary	Progression free survival (PFS)	PFS will be assessed using Kaplan-Meier product limit estimates and compared between patients with obinutuzumab maintenance versus without maintenance using the log-rank test. Longitudinal data of neurocognitive function and QOL will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.	From the start date of first-line primary central nervous system lymphoma (PCNSL) treatment to disease progression or death, assessed up to 2 years
Secondary	Overall survival	OS will be assessed using Kaplan-Meier product limit estimates and compared between patients with obinutuzumab maintenance versus without maintenance using the log-rank test. Longitudinal data of neurocognitive function and QOL will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.	From the start date of first-line PCNSL treatment to death, assessed up to 2 years.
Secondary	Neurocognitive function - Hopkins Verbal Learning Test-Revised	Will be measured by the Hopkins Verbal Learning Test-Revised. Test evaluates total recall, delayed recall, percent of retention, and recognition. Higher score means better outcome. Longitudinal data of neurocognitive function will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.	Up to 2 years
Secondary	Neurocognitive function - Grooved Pegboard Test	Will be measured by the Grooved Pegboard Test. Scale 0 seconds to time of completion in minutes and seconds. Higher time to completion means worse outcome. Longitudinal data of neurocognitive function will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.	Up to 2 years
Secondary	Neurocognitive function - Trail Making Test	Will be measured by the Trail Making Test. Scale Part A: 0 seconds to 100 seconds (time of greater than 100 seconds discontinues the test. Scale Part B: 0 seconds to 300 seconds (time of greater than 300 seconds discontinues the test. Number of errors recorded. Higher time to completion and greater number of errors means worse outcome. Longitudinal data of neurocognitive function will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.	Up to 2 years
Secondary	Neurocognitive function - Brief Test of Attention	Will be measured by the Trail Making Test. Scale 0 to 20 points. Higher score mean better outcome. Longitudinal data of neurocognitive function will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.	Up to 2 years
Secondary	Quality of life (QOL) - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item	Will be measured by the European Organization for Research and Treatment of Cancer Quality of Life Core 30-item (EORTC QLQ-C30) questionnaire. Scale 30 to 126 points. Higher score means worse outcome. Longitudinal data of QOL will be analyzed using a linear mixed model and toxicity indicators will be assessed using a chi-square or exact test.	Up to 2 years