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

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ClinicalTrials.gov Identifier: NCT02498951
Recruitment Status : Recruiting
First Posted : July 15, 2015
Last Update Posted : September 20, 2018
Sponsor:
Collaborators:
Genentech, Inc.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Edward Neuwelt, OHSU Knight Cancer Institute

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

Condition or disease Intervention/treatment Phase
CD20 Positive Central Nervous System B-Cell Non-Hodgkin Lymphoma Procedure: Cognitive Assessment Biological: Obinutuzumab Other: Quality-of-Life Assessment Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Maintenance Obinutuzumab for Primary Central Nervous System Lymphoma Complete Responders
Actual Study Start Date : July 12, 2016
Estimated Primary Completion Date : April 18, 2021
Estimated Study Completion Date : April 18, 2022


Arm Intervention/treatment
Experimental: Arm I (obinutuzumab)
Patients 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.
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

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Active Comparator: Arm II (observation)
Patients undergo observation for a total of 3 years.
Procedure: Cognitive Assessment
Ancillary studies

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02498951


Locations
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United States, Colorado
University of Colorado Recruiting
Denver, Colorado, United States, 80217-3364
Contact: Douglas E. Ney    720-848-0650      
Principal Investigator: Douglas E. Ney         
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Larry R. Junck    800-865-1125    ljunck@med.umich.edu   
Principal Investigator: Larry R. Junck         
United States, North Carolina
Comprehensive Cancer Center of Wake Forest University Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Roy E. Strowd    336-713-5440    rstrowd@wakehealth.edu   
Principal Investigator: Roy E. Strowd         
United States, Ohio
Cleveland Clinic Cancer Center/Fairview Hospital Recruiting
Cleveland, Ohio, United States, 44111
Contact: David M. Peereboom    216-445-6068    peerebd@ccf.org   
Principal Investigator: David M. Peereboom         
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Edward A. Neuwelt    503-494-5626    neuwelte@ohsu.edu   
Principal Investigator: Edward A. Neuwelt         
United States, Pennsylvania
Penn State Milton S Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Michael J. Glantz, MD    717-531-0003    mglantz@pennstatehealth.psu.edu   
Principal Investigator: Michael Glantz, MD         
United States, Rhode Island
Rhode Island Hospital (Brown University) Recruiting
Providence, Rhode Island, United States, 02912
Contact: Alexander Mohler    401-444-3234    Alexander.mohler@lifespan.org   
Principal Investigator: Alexander Mohler         
United States, Texas
University of Texas Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Edward Pan, MD    214-645-4673    Edward.pan@utsouthwestern.edu   
Principal Investigator: Edward Pan, MD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22903
Contact: David Schiff, MD    434-924-5610    Ds4jd@hscmail.mcc.virginia.edu   
Principal Investigator: David Schiff, MD         
Sponsors and Collaborators
OHSU Knight Cancer Institute
Genentech, Inc.
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Edward Neuwelt OHSU Knight Cancer Institute

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Responsible Party: Edward Neuwelt, Professor, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT02498951     History of Changes
Other Study ID Numbers: 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 )
First Posted: July 15, 2015    Key Record Dates
Last Update Posted: September 20, 2018
Last Verified: September 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Obinutuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents