Multicenter Phase II Study of the Bendamustine, Obinutuzumab, and Dexamethasone (BOD) Regimen in Un-fit Elderly ≥ 70 Years of Age Diffuse Large B-Cell Non-Hodgkin Lymphoma (DLBCL) Patients
Overview
- Phase
- Phase 2
- Intervention
- Bendamustine Hydrochloride
- Conditions
- Diffuse Large B-Cell Lymphoma
- Sponsor
- University of Chicago
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- ORR (PR + CR) Using the Cheson et al Parameters
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
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.
Detailed Description
PRIMARY OBJECTIVES: I. Assess the overall response rate (ORR; complete responders \[CR\] + partial responders \[PR\]) using the Cheson et al parameters of this novel combination regimen. SECONDARY OBJECTIVES: I. Assess the feasibility of incorporating prospective geriatric assessments in patients \>= 70 years of age diagnosed with diffuse large B-cell lymphoma (DLBCL) and treated in a multi-center setting. II. Quality of life (QOL) based on Functional Assessment of Cancer Therapy-Lung (FACT-L) scale on all enrolled patients. III. Progression-free survival (PFS) at 2 and 3 years. IV. Overall survival (OS) at 2 and 3 years. OUTLINE: Patients receive bendamustine hydrochloride intravenously (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 orally (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. After completion of study treatment, patients are followed up every 6 months for 40 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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:
Arms & Interventions
Treatment (bendamustine, obinutuzumab, dexamethasone)
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.
Intervention: Bendamustine Hydrochloride
Treatment (bendamustine, obinutuzumab, dexamethasone)
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.
Intervention: Obinutuzumab
Treatment (bendamustine, obinutuzumab, dexamethasone)
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.
Intervention: Dexamethasone
Treatment (bendamustine, obinutuzumab, dexamethasone)
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.
Intervention: Quality-of-Life Assessment
Treatment (bendamustine, obinutuzumab, dexamethasone)
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.
Intervention: Laboratory Biomarker Analysis
Outcomes
Primary Outcomes
ORR (PR + CR) Using the Cheson et al Parameters
Time Frame: Up to 8 months
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
Secondary Outcomes
- 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)