Bendamustine, Obinutuzumab, and Dexamethasone in Older Patients With Diffuse Large B-cell Lymphoma

NCT02420210 | Terminated Phase 2 Results

• 3 other identifiers: IRB14-1120NCI-2015-00355P30CA014599
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well bendamustine hydrochloride, obinutuzumab, and dexamethasone work in treating older patients with diffuse large B-cell lymphoma. Drugs used in chemotherapy, such as bendamustine hydrochloride and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as obinutuzumab, may find cancer cells and help kill them. Giving bendamustine hydrochloride, obinutuzumab, and dexamethasone may kill more cancer cells.

Conditions

Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• ORR (PR + CR) Using the Cheson et al Parameters

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  Up to 8 months

Secondary Outcomes (5)

• Feasibility, Defined as Completing All Required Geriatric Assessments Where Applicable Per the Protocol in 80% or More of the Enrolled Eligible Patients

  Up to 40 months

• Overall Survival

  From date of study entry (date of first treatment) until death from any cause, assessed at 2 years

• Overall Survival (OS)

  From date of study entry (date of first treatment) until death from any cause, assessed at 3 years

• Progression Free Survival

  From date of study entry (date of first treatment) until progression, secondary malignancy, or death from any cause, assessed at 2 years

• Incidence of Toxicity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  Up to 30 days following the last administration of study treatment

Other Outcomes (1)

• Quality of Life Assessed Using the Functional Assessment of Cancer Therapy (FACT)-L Scale

  Up to 18 weeks (at end of study treatment)

Study Arms (1)

Treatment (bendamustine, obinutuzumab, dexamethasone)

EXPERIMENTAL

Patients receive bendamustine hydrochloride IV over 30 minutes on days 1 and 2, obinutuzumab IV over 4 hours on days 1 or 2, 8, and 15 (on both days 1 and 2 in course 1 only), dexamethasone PO daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Bendamustine Hydrochloride; Biological: Obinutuzumab; Drug: Dexamethasone; Other: Quality-of-Life Assessment; Other: Laboratory Biomarker Analysis

Interventions

Bendamustine Hydrochloride DRUG

Given IV

Also known as: Ribomustin, SyB L-0501, Treanda

Treatment (bendamustine, obinutuzumab, dexamethasone)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA101, Gazyva, R7159, RO 5072759

Treatment (bendamustine, obinutuzumab, dexamethasone)

Dexamethasone DRUG

Given PO

Also known as: DM

Treatment (bendamustine, obinutuzumab, dexamethasone)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (bendamustine, obinutuzumab, dexamethasone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (bendamustine, obinutuzumab, dexamethasone)

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Histologically confirmed DLBCL, cluster of differentiation (CD)20 positive by flow or immunohistochemistry (IHC); transformed DLBCL is allowed as long as no prior therapy has been given
• No prior therapy for DLBCL, except =\< 1 week of corticosteroids given on an emergent basis or as a temporizing measure (pre-phase where indicated by the treating physician)
• Measurable disease by computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) with at least one target lesion measuring 1.5 cm or larger
• Patients must be considered ineligible for rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone (R-CHOP) standard therapy; to be ineligible for R-CHOP, patients must meet at least one of the following criteria are met:
• Prior anthracycline therapy for other malignancies or other disorders whereby if additional anthracyclines are given for DLBCL, the maximum lifetime allowable dose will be exceeded
• Meeting the geriatric criteria of ineligibility for standard R-CHOP if one of the following criteria is present:
• Three or more organ systems with a score of 3 or any 1 organ system with a score of 4 (using the Cumulative Illness Rating Scale for Geriatrics, \[CIRS-G\])
• Score of 3 or above on the Vulnerable Elders Survey (VES-13)
• Score of =\< 9 in the short physical performance battery (SPPB)
• Presence of a significant geriatric syndrome (dementia, delirium, falls, incontinence, malnutrition, and severe osteoporosis) in the past year prior to diagnosis
• Any abnormality in performing activities of daily living (ADLs) or instrumental activities of daily living (IADLs)
• Absolute neutrophil count (ANC) \>= 1.5 unless cytopenias are related to bone marrow involvement with disease
• Hemoglobin \>= 7 g/dl unless cytopenias are related to bone marrow involvement with disease
• Platelets \>= 75,000 unless cytopenias are related to bone marrow involvement with disease
• Glomerular filtration rate (GFR) \> 30 using Cockcroft-Gault formula

You may not qualify if:

• Prior therapy for DLBCL
• Other non-Hodgkin lymphoma (NHL) histologies
• Known central nervous system (CNS) involvement
• Known human immunodeficiency virus (HIV) or human T-lymphotropic virus, type I (HTLV-I) positive status
• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per treating investigator assessment)
• Treatment with any known non-marketed drug substance or experimental therapy within 4 weeks prior to enrollment, or currently participating in any other interventional clinical study for NHL or any other illness (except observational and registry trials)
• Other past or current malignancy; subjects who have been free of malignancy for at least 3 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma (any site) are eligible; women with a history of cervical cancers are allowed
• Chronic or current infectious disease requiring systemic antibiotics, antifungal (excluding antifungals given for nail-beds infections), or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis C
• History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
• Positive hepatitis serology:
• Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C antibody (HCAb)
• Inability to comply with study or follow-up testing and procedures
• Prior radiotherapy is allowed if it was given for low-grade lymphoma before transformation in those with transformed NHL and as long as no chemotherapy was administered in conjunction with radiation
• Any patient receiving a live vaccine must allow a 4-week interval before starting treatment on this study
• Known hypersensitivity to mannitol

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Bendamustine Hydrochloride; obinutuzumab; Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Theodore Karrison
• Organization: University of Chicago

tkarrison@health.bsd.uchicago.edu

773-702-9326

Study Officials

• Ken Cohen

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2015
• First Posted: April 17, 2015
• Study Start: November 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: June 6, 2018
• Results First Posted: March 14, 2018

Record last verified: 2018-05

Locations

US (1)