Clinical Trials /

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

NCT02498951

Description:

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.

Related Conditions:
  • Primary Central Nervous System Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Obinutuzumab in Treating Patients With Central Nervous System Lymphoma Who Have Achieved a Complete Response
  • Official Title: Maintenance Obinutuzumab for Primary Central Nervous System Lymphoma Complete Responders

Clinical Trial IDs

  • ORG STUDY ID: IRB00011601
  • SECONDARY ID: NCI-2015-01014
  • SECONDARY ID: ML29496
  • SECONDARY ID: IRB00011601
  • SECONDARY ID: P30CA069533
  • SECONDARY ID: R01CA137488
  • NCT ID: NCT02498951

Conditions

  • CD20 Positive
  • Central Nervous System B-Cell Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
ObinutuzumabAnti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759Arm I (obinutuzumab)

Purpose

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). Monoclonal antibodies, such as obinutuzumab, may kill cancer cells that are left after chemotherapy.

Detailed Description

      PRIMARY OBJECTIVES:

      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 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 course, and on day 1 for the subsequent courses. Courses 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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (obinutuzumab)ExperimentalPatients receive obinutuzumab IV on days 1 and 2 for the first course, and on day 1 for the subsequent courses. Courses repeat every 60 days for 2 years in the absence of disease progression or unacceptable toxicity.
  • Obinutuzumab
Arm II (observation)Active ComparatorPatients undergo observation for a total of 3 years.

    Eligibility Criteria

            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
    
              -  Fertile men or women of childbearing potential unless 1) surgically sterile or 2)
                 using an adequate measure of contraception such as oral contraceptives, intrauterine
                 device, or barrier method of contraception in conjunction with spermicidal jelly
    
              -  Effective contraception is required while receiving obinutuzumab; for women, effective
                 contraception is required to continue for >= 12 months after the last dose of
                 obinutuzumab; for men, effective contraception is required to continue for 3 months
                 after the last dose of obinutuzumab treatment
    
              -  Vaccination with a live vaccine a minimum of 4 weeks prior to study enrollment
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure: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
    Safety Issue:
    Description: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.

    Secondary Outcome Measures

    Measure: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
    Safety Issue:
    Description: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.
    Measure:Neurocognitive function measured by the Wechsler Adult Intelligence Scale, Hopkins Verbal Learning Test-Revised, and Grooved Pegboard Test
    Time Frame:Up to 3 years
    Safety Issue:
    Description: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.
    Measure: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
    Safety Issue:
    Description: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.
    Measure: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
    Safety Issue:
    Description: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.
    Measure:Overall survival
    Time Frame:From the start date of first-line PCNSL treatment to death, assessed up to 3 years
    Safety Issue:
    Description: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.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:OHSU Knight Cancer Institute

    Last Updated

    September 19, 2018