Clinical trial NCT01680991: A Study of Obinutuzumab in Chinese Participants With CD20+ Malignant Disease
Official title: A Multi-Center, Open Label, Single Arm, Multiple Dose Study to Assess the Pharmacokinetics of RO5072759 in Chinese Patients With CD20+ Malignant Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphocytic Leukemia, Chronic, Diffuse Large B-cell Lymphoma, Follicular Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-09-07
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multi-center, open-label, single-arm study will evaluate the pharmacokinetics and safety of obinutuzumab in participants with cluster of differentiation (CD) 20 positive (+) malignant disease. Participants will receive multiple doses of obinutuzumab. The anticipated time on study treatment is 24 weeks.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of CD20+ B-cell lymphoma or B-CLL
* Refractory/relapsed CLL, FL, and DLBCL
* At least 1 measurable lesion (greater than \[\>\] 1.5 centimeters \[cm\] in its largest dimension) with the exception of CLL
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy \>6 months

Exclusion Criteria:

* Prior use of any investigational antibody therapy within 6 months of study start
* Prior use of any anti-cancer vaccine
* Prior administration of rituximab within 3 months of study start
* Prior administration of radioimmunotherapy 3 months prior to study entry
* Central nervous system lymphoma
* History of other malignancy
* Evidence of significant, uncontrolled concomitant disease
* Abnormal laboratory values
* Patients with progressive multifocalleukoencephalopathy (PML)
* Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C

Primary outcomes:
measure: Area Under the Serum Concentration Time Curve From Zero to Day 7 (AUC0-7) of Obinutuzumab on Day 1, Cycle 1
timeFrame: Cycle 1-NHL: within 2 hours (h) pre-dose (Pr-D), end of infusion (EoI), 4, 24, 72 and 120 h post-infusion (Po-I) on Day 1; CLL: within 2 h Pr-D, EoI on Days 1,2; 4, 24, 72 and 120 h Po-I on Day 2. NHL and CLL: within 2 h Pr-D on Day 8
measure: Maximum Observed Serum Concentration (Cmax) of Obinutuzumab on Day 1, Cycle 1
timeFrame: Cycle 1-NHL: within 2 h Pr-D, EoI, 4, 24, 72 and 120 h Po-I on Day 1; CLL: within 2 h Pr-D, EoI on Days 1,2; 4, 24, 72 and 120 h Po-I on Day 2. NHL and CLL: within 2 h Pr-D on Day 8
measure: Area Under the Serum Concentration Versus Time Curve From 0 to Day 21 (AUC0-21) of Obinutuzumab at Cycle 8
timeFrame: Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1
measure: Cmax of Obinutuzumab at Cycle 8
timeFrame: Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1
Secondary outcomes:
measure: Time to Maximum Observed Serum Concentration (Tmax) of Obinutuzumab at Cycle 8
timeFrame: Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1
measure: Apparent Terminal Half-life (t1/2)
timeFrame: Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1, 4-week follow-up (Day 29), 3 and 6 months after Cycle 8 dosing
measure: Volume of Distribution at Steady State (Vss) of Obinutuzumab at Cycle 8
timeFrame: Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1
measure: Total Systemic Clearance at Steady State (CLss) of Obinutuzumab at Cycle 8
timeFrame: Cycle 8: within 2 h Pr-D, EoI, 4, 24, 72, 120, 168, 336 (Day 15), and 504 (Day 22) h Po-I on Day 1
measure: Minimum Observed Serum Concentration of Obinutuzumab
timeFrame: Within 2 hours Pr-D on Day 1 of Cycles 2-8 and on Days 8,15 of Cycle 1
measure: Percentage of Participants With Complete Response (CR), CR Unconfirmed (CRu) at End of Treatment (1 Month After Cycle 8) in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria
timeFrame: 1 month after the last dose (received on Day 148) of study drug
measure: Percentage of Participants With Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) at End of Treatment (1 Month After Cycle 8) in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria
timeFrame: 1 month after the last dose (received on Day 148) of study drug
measure: Percentage of Participants With Best Overall Response (BOR) of CR, CRu at Anytime During Study in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria
timeFrame: From screening to up to 1 month after the last dose (received on Day 148) of study drug
measure: Percentage of Participants With BOR of PR, SD, and PD at Anytime During Study in NHL Participants (DLBCL and FL Participants) Per Cheson 1999 Criteria
timeFrame: From screening to up to 1 month after the last dose (received on Day 148) of study drug
measure: Percentage of Participants With Complete Remission (CRe), CRe With Incomplete BM Recovery (CRi) at End of Treatment (1 Month After Cycle 8) in CLL Participants According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Guidelines
timeFrame: 2 months after the last dose (received on Day 148) of study drug
measure: Percentage of Participants With PR, SD, and PD at End of Treatment (1 Month After Cycle 8) in CLL Participants According to IWCLL 2008 Guidelines
timeFrame: 2 months after the last dose (received on Day 148) of study drug
measure: Percentage of Participants With BOR of CRe, CRi at Anytime During the Study in CLL Participants According to IWCLL 2008 Guidelines
timeFrame: From screening to up to 2 months after the last dose (received on Day 148) of study drug
measure: Percentage of Participants With BOR of PR, SD, and PD at Anytime During Study in CLL Participants According to IWCLL 2008 Guidelines
timeFrame: From screening to up to 2 months after the last dose (received on Day 148) of study drug
measure: Number of Participants With Positive Human Anti-Human Antibodies (HAHA)
timeFrame: Cycle 1 (Day 1), Cycle 4 (Day 1), 4-week follow-up, 3 and 6 month follow-up
measure: Number of Participants With Positive Human Anti-Chimeric Antibodies (HACA)
timeFrame: Cycle 1, Day 1
measure: Number of Participants With B-cell Depletion or Recovery
timeFrame: Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year
measure: Duration of Depletion of CD19+ B-cell
timeFrame: Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year
measure: Time to Recovery of CD19+ B-cell
timeFrame: Screening, Cycle 1 (Days 1,8), Cycle 2 (Day 1), Cycle 4 (Day 1), Cycle 6 (Day 1), Cycle 8 (Day 1), 4 weeks after last dose of study drug and every 3 months after last dose of study drug up to 1 year
Other outcomes:
Locations:
city: Beijing
country: China
city: Beijing
country: China
city: Guangzhou
country: China
city: Shanghai
country: China
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Qin Y, Song Y, Shen Z, Du X, Ji W, Hsu W, Zhu J, Shi Y. Safety and efficacy of obinutuzumab in Chinese patients with B-cell lymphomas: a secondary analysis of the GERSHWIN trial. Cancer Commun (Lond). 2018 May 30;38(1):31. doi: 10.1186/s40880-018-0300-5.
citation: Zhai J, Qin Y, Zhu J, Song Y, Shen Z, Du X, Jamois C, Brewster M, Shi Y, Shi J. Pharmacokinetics of obinutuzumab in Chinese patients with B-cell lymphomas. Br J Clin Pharmacol. 2017 Jul;83(7):1446-1456. doi: 10.1111/bcp.13232. Epub 2017 Feb 14.