Clinical trial NCT02320487: A Study of Obinutuzumab + Bendamustine (BG) in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL)
Official title: A Phase II, Open-Label Study of Obinutuzumab Plus Bendamustine (BG) in Patients With Previously Untreated Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2014-12-19
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, open-label, multicenter study to evaluate the safety and efficacy of BG induction therapy in participants with previously untreated CLL. The anticipated time on study treatment is 24 weeks.


Eligibility criteria: Inclusion Criteria:

* Participants must satisfy one of the criteria for treatment initiation, as outlined in the iwCLL NCI-WG guidelines. The criteria include: (a) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia, (b) Massive (i.e., greater than or equal to \[\>=\] 6 centimeters \[cm\] below the left costal margin) or progressive or symptomatic splenomegaly, (c) Massive nodes (i.e., \>= 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy, (d) Progressive lymphocytosis with an increase of greater than (\>) 50 percent (%) over a 2-month period or lymphocyte doubling time (LDT) of less than (\<) 6 months, (e) Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy, (f) Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: unintentional weight loss of \>=10% within the previous 6 months, significant fatigue (i.e., Eastern Cooperative Oncology Group Performance Status \[ECOG PS\] of 2 or worse or the inability to work or perform usual activities), fevers higher than 100.5 degrees Fahrenheit (°F)/38.0 degrees Celsius (°C) for \>= 2 weeks without other evidence of infection, or night sweats for \>1 month without evidence of infection
* Absolute neutrophil count (ANC) \>=1.5 × 10\^9 per liter (/L) and platelets \>=75 × 10\^9/L unless cytopenia is caused by the underlying disease, i.e., no evidence of additional bone marrow dysfunction (e.g., myelodysplastic syndrome, hypoplastic bone marrow)
* Life expectancy \>6 months
* ECOG PS of 0, 1, or 2
* Willing to use acceptable contraceptive measures as defined by the protocol during and at least for 6 months (male participants) or 12 months (female participants) after the last dose of study drug

Exclusion Criteria:

* Pregnant or lactating, or intending to become pregnant during the study: Women who are not postmenopausal (\>=12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug
* Participants who have received previous CLL therapy, including investigational therapies
* Transformation of CLL to aggressive non-Hodgkin's lymphoma (Richter's transformation)
* Inadequate renal function
* Inadequate liver function: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 3 liver function tests (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] \>5× upper limit of normal \[ULN\] for \>2 weeks; bilirubin \>3× ULN) unless due to underlying disease
* History of other malignancy, which could affect compliance with the protocol or interpretation of results
* Participants with active bacterial, viral, or fungal infection requiring systemic treatment
* Participants with known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1)
* Positive hepatitis serology: (a) Participants with positive serology for hepatitis B, defined as positivity for hepatitis B surface antigen (HBsAg), or participants who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive, (b) Participants positive for anti-HBc, but with negative hepatitis B Virus (HBV) deoxyribonucleic acid (DNA), will be considered for inclusion by the Medical Monitor on a case-by-case basis in order to ensure feasibility of monthly DNA testing and availability of appropriate care in case of hepatitis B reactivation, (c) Participants with positive serology for hepatitis C (HCV) unless HCV (by ribonucleic acid \[RNA\]) is confirmed negative
* History of severe allergic or anaphylactic reactions to monoclonal antibodies
* Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of symptomatic bronchospasm)
* Vaccination with a live vaccine a minimum of 30 days prior to study treatment
* Use of investigational agents of any kind within 30 days before study treatment

Primary outcomes:
measure: Percentage of Participants With Complete Response (CR), as Determined by the Investigator Using International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (iwCLL NCI-WG) Guidelines
timeFrame: 2 to 3 months after the last infusion of study treatment (up to approximately 228 to 258 days)
Secondary outcomes:
measure: Percentage of Participants With Objective Response of CR or Partial Response (PR) at the End of Induction Therapy, as Determined by the Investigator Using iwCLL NCI-WG Guidelines
timeFrame: 2 to 3 months after the last infusion of study treatment (up to approximately 228 to 258 days)
measure: Duration of Response Among Participants With Objective Response of CR or PR, as Determined by the Investigator Using iwCLL NCI-WG Guidelines
timeFrame: From the first assessment of CR, CRi, PR, or nPR (at up to approximately 228 to 258 days) until disease progression, relapse, or death from any cause, whichever occurred first (up to 46 months)
measure: Progression-Free Survival (PFS), as Determined by the Investigator Using iwCLL NCI-WG Guidelines
timeFrame: Day 1 until disease progression, relapse, or death from any cause, whichever occurred first (up to 46 months)
measure: Overall Survival (OS)
timeFrame: Day 1 until death from any cause (up to 46 months)
measure: Percentage of Participants Who Achieved Minimal Residual Disease (MRD)-Negative Status in Bone Marrow at Any Time During the Study
timeFrame: Up to 46 months
measure: Percentage of Participants Who Achieved MRD-Negative Status in Peripheral Blood at Any Time During the Study
timeFrame: Baseline up to 46 months
measure: Time to MRD-Negative Status in Peripheral Blood
timeFrame: Baseline up to 46 months
measure: Duration of MRD-Negativity in Peripheral Blood Among Participants Who Achieved MRD-Negative Status
timeFrame: Baseline up to 46 months
measure: Minimum Observed Concentration (Ctrough) of Obinutuzumab After Cycle 2
timeFrame: Pre-infusion (0 hours) on Day 1 Cycle 3 (1 cycle = 28 days)
measure: Ctrough of Obinutuzumab After Cycle 4
timeFrame: Pre-infusion (0 hours) on Day 1 Cycle 5 (1 cycle = 28 days)
measure: Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
timeFrame: Day 1 Cycles 1 (baseline), 3, 6; end of treatment, 2 months after last dose, every 3 months thereafter for 2 years (up to 46 months) (1 cycle = 28 days)
measure: Change From Baseline in the EORTC Quality of Life Questionnaire-Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) Score
timeFrame: Day 1 Cycles 1 (baseline), 3, 6; end of treatment, 2 months after last dose, every 3 months thereafter for 2 years (up to 46 months) (1 cycle = 28 days)
measure: Number of Hospitalizations Due to Adverse Events (AEs)
timeFrame: Day 1 up to 46 months
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Day 1 up to 46 months
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Institute
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center - Mobile
state: Alabama
city: Chandler
country: United States
facility: Ironwood Cancer TX & Rsch Ctrs
state: Arizona
city: Tempe
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Aurora
country: United States
facility: Rocky Mountain Cancer Center - Aurora
state: Colorado
city: Fort Collins
country: United States
facility: Cancer Care and Hematology
state: Colorado
city: Atlanta
country: United States
facility: Piedmont Cancer Institute, PC
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC - Marietta
state: Georgia
city: Niles
country: United States
facility: Cancer Care & Hematology; Specialists of Chicagoland
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Med Oncology & Hematology Inc
state: Indiana
city: Bethesda
country: United States
facility: Center For Cancer and Blood Disorders
state: Maryland
city: Morristown
country: United States
facility: Regional Cancer Care Associates LLC - Morristown
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Portland
country: United States
facility: Northwest Cancer Specialists - Portland (N Broadway)
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Springfield
country: United States
facility: Willamette Valley Cancer Insitute and Research Center
state: Oregon
city: Arlington
country: United States
facility: Texas Oncology-Arlington
state: Texas
city: Irving
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research & Treatment Center
state: Texas
city: New Braunfels
country: United States
facility: Cancer Care Centers of South Texas-HOAST - San Antonio
state: Texas
city: Ogden
country: United States
facility: Northern Utah Associates
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/North Star Lodge
state: Washington
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Sharman JP, Burke JM, Yimer HA, Boxer MA, Babu S, Li J, Mun Y, Danilov AV; GIBB study investigators. Phase 2, multicenter GIBB study of obinutuzumab plus bendamustine in previously untreated patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2021 Apr;62(4):791-800. doi: 10.1080/10428194.2020.1850719. Epub 2020 Nov 26.