Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02498951
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02498951
Recruitment Status : Recruiting
First Posted : July 15, 2015
Last Update Posted : May 7, 2020
Sponsor:
Collaborators:
Genentech, Inc.
National Cancer Institute (NCI)
Oregon Health and Science University
Information provided by (Responsible Party):
Edward Neuwelt, OHSU Knight Cancer Institute

Tracking Information
First Submitted Date  ICMJE July 13, 2015
First Posted Date  ICMJE July 15, 2015
Last Update Posted Date May 7, 2020
Actual Study Start Date  ICMJE July 12, 2016
Estimated Primary Completion Date January 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 11, 2018)
Complete response (CR) duration [ Time Frame: From the date of brain magnetic resonance imaging (MRI) after completion of first-line treatment which confirms CR, to disease progression or death, assessed up to 3 years ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2015)
CR duration [ Time Frame: From the date of brain MRI after completion of first-line treatment which confirms CR, to disease progression or death, assessed up to 3 years ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 5, 2020)
  • Overall survival (OS) after CR [ Time Frame: From the date of brain MRI after completion of first-line treatment which confirms CR, to death, assessed up to 3 years ]
    OS after 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.
  • Neurocognitive function [ Time Frame: Up to 3 years ]
    Will be measured by the Wechsler Adult Intelligence Scale, Hopkins Verbal Learning Test-Revised, and Grooved Pegboard Test. 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.
  • Quality of life (QOL) [ Time Frame: Up to 3 years ]
    Will be measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 and Brain Cancer Module-20. 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.
  • Progression free survival (PFS) [ Time Frame: From the start date of first-line primary central nervous system lymphoma (PCNSL) treatment to disease progression or death, assessed up to 3 years ]
    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.
  • Overall survival [ Time Frame: From the start date of first-line PCNSL treatment to death, assessed up to 3 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2015)
  • Neurocognitive function measured by the Wechsler Adult Intelligence Scale, Hopkins Verbal Learning Test-Revised, and Grooved Pegboard Test [ Time Frame: Up to 3 years ]
    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.
  • Overall survival [ Time Frame: From the start date of first-line PCNSL treatment to death, assessed up to 3 years ]
    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.
  • Overall survival after CR [ Time Frame: From the date of brain MRI after completion of first-line treatment which confirms CR, to death, assessed up to 3 years ]
    OS after 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.
  • Progression free survival [ Time Frame: From the start date of first-line PCNSL treatment to disease progression or death, assessed up to 3 years ]
    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.
  • Quality of life (QOL) measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 and Brain Cancer Module-20 [ Time Frame: Up to 3 years ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Maintenance Obinutuzumab in Treating Patients With Central Nervous System Lymphoma Who Have Achieved a Complete Response
Official Title  ICMJE Maintenance Obinutuzumab for Primary Central Nervous System Lymphoma Complete Responders
Brief 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). Immunotherapy with obinutuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread.
Detailed Description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

I. To evaluate overall survival after CR (overall survival [OS]-CR). 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 3 years.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Central Nervous System B-Cell Non-Hodgkin Lymphoma
Intervention  ICMJE
  • Procedure: Cognitive Assessment
    Ancillary studies
  • Biological: Obinutuzumab
    Given IV
    Other Names:
    • Anti-CD20 Monoclonal Antibody R7159
    • GA-101
    • GA101
    • Gazyva
    • huMAB(CD20)
    • R7159
    • RO 5072759
    • RO-5072759
    • RO5072759
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
Study Arms  ICMJE
  • Experimental: Arm I (obinutuzumab)
    Patients receive obinutuzumab IV on days 1 and 2 for the first cycle, and on day 1 for the subsequent cycles, 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
    Interventions:
    • Procedure: Cognitive Assessment
    • Biological: Obinutuzumab
    • Other: Quality-of-Life Assessment
  • Active Comparator: Arm II (observation)
    Patients undergo observation for a total of 3 years.
    Interventions:
    • Procedure: Cognitive Assessment
    • Other: Quality-of-Life Assessment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 13, 2015)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2025
Estimated Primary Completion Date January 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 complete response (CR/unconfirmed complete response [CRu]) to first-line treatment
  • Brain magnetic resonance imaging (MRI) documenting CR 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 >= 12 months after the last dose of obinutuzumab for women, and 3 months 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02498951
Other Study ID Numbers  ICMJE IRB00011601
NCI-2015-01014 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ML29496
IRB00011601 ( Other Identifier: OHSU Knight Cancer Institute )
P30CA069533 ( U.S. NIH Grant/Contract )
R01CA137488 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Edward Neuwelt, OHSU Knight Cancer Institute
Study Sponsor  ICMJE OHSU Knight Cancer Institute
Collaborators  ICMJE
  • Genentech, Inc.
  • National Cancer Institute (NCI)
  • Oregon Health and Science University
Investigators  ICMJE
Principal Investigator: Edward A Neuwelt OHSU Knight Cancer Institute
PRS Account OHSU Knight Cancer Institute
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP