A Study of Obinutuzumab in Combination With Chemotherapy in Participants With CD20+ B-Cell Follicular Non-Hodgkin's Lymphoma

Non-Hodgkin's Lymphoma Clinical Trial

— GAUDI  

Official title:

An Open-Label, Multi-Centre, Randomised, Phase Ib Study to Investigate the Safety and Efficacy of RO5072759 Given in Combination With CHOP, FC or Bendamustine Chemotherapy in Patients With CD20+ B-Cell Follicular Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00825149
• Other study ID #: BO21000
• Secondary ID: 2008-001643-19
• Status: Completed
• Phase: Phase 1
• First received: January 16, 2009
• Last updated: November 3, 2016
• Start date: February 2009
• Est. completion date: November 2015

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This open-label, randomized, phase Ib study will assess the safety and efficacy of obinutuzumab given in combination with FC (fludarabine and cyclophosphamide) or CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) or bendamustine induction chemotherapy in participants with Cluster of Differentiation (CD) 20+ B-cell Follicular Lymphoma (FL). Participants with complete response or partial response after induction therapy may receive maintenance therapy every 3 months for 2 years or until disease progression, whichever comes first. All participants in the induction period of the study will have a safety follow-up visit 28 days after completing the last dose of obinutuzumab + chemotherapy, and will be followed for at least 2 years, unless they are being treated in maintenance or discontinue from the study prior to this time point. Participants who complete/discontinue maintenance therapy will also be followed for a period of 2 years after receiving the last dose of obinutuzumab or until progression/new antilymphoma treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 137
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Either CD20+ R/R B-cell follicular non-Hodgkin's lymphoma (after a maximum of 2 prior chemotherapy regimens) or CD20+ B-cell follicular non-Hodgkin's lymphoma with no prior systemic therapy

• Must have at least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters [cm] in its largest dimension by computed tomography [CT] scan)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria:

• For R/R participants recruited in Obinutuzumab + CHOP regimen, prior use of anthracyclines. For R/R participants recruited in Obinutuzumab + FC regimen, immediate prior treatment should not have contained fludarabine or fluoropyrimidines. For first-line recruited participants, prior systemic therapy

• Prior administration of rituximab within 56 days of study entry, or 3 months for any radioimmunotherapy

• Central nervous system lymphoma

• History of other malignancies within 2 years of study entry which could affect compliance with the protocol or interpretation of results

• Known active bacterial, viral (including human immunodeficiency virus [HIV]), fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing

• Contraindication to any of the individual components of chemotherapy (as per local prescribing information), of the selected chemotherapy combination (FC, CHOP or bendamustine)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• Bendamustine
Bendamustine will be administered as per schedule specified in the respective arm.
• Cyclophosphamide
Cyclophosphamide will be administered as per schedule specified in the respective arm.
• Doxorubicin
Doxorubicin will be administered as per schedule specified in the respective arm.
• Fludarabine
Fludarabine will be administered as per schedule specified in the respective arm.
• Obinutuzumab
Obinutuzumab will be administered as per schedule specified in the respective arm.
• Prednisone
Prednisone will be administered as per schedule specified in the respective arm.
• Vincristine
Vincristine will be administered as per schedule specified in the respective arm.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Australia,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (AEs) - Relapsed/Refractory Population		Baseline up to maximum observation time of 79.5 months	No
Primary	Percentage of Participants With AEs - First-line Population		Baseline up to maximum observation time of 59.7 months	No
Secondary	Percentage of Participants With End of Induction Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population		28 days after end of induction treatment (up to 28 weeks)	No
Secondary	Percentage of Participants With End of Induction Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population		28 days after end of induction treatment (up to 28 weeks)	No
Secondary	Percentage of Participants With Best Overall Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population		Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 79.5 months)	No
Secondary	Percentage of Participants With Best Overall Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population		Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 59.7 months)	No
Secondary	Percentage of Participants With Best Overall Response of Complete Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population		Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 79.5 months)	No
Secondary	Percentage of Participants With Best Overall Response of Complete Response, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population		Baseline up to initiation of new anti-lymphoma therapy or end of study (up to a maximum observation time of 59.7 months)	No
Secondary	Number of Participants With Progression-Free Survival (PFS) Events (Disease Progression/Relapse or Death), According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population		Baseline up to disease progression or death (up to maximum observation time of 79.5 months)	No
Secondary	Number of Participants With PFS Events (Disease Progression/Relapse or Death), According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population		Baseline up to disease progression or death (up to maximum observation time of 59.7 months)	No
Secondary	PFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population		Baseline up to disease progression or death (up to maximum observation time of 79.5 months)	No
Secondary	PFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population		Baseline up to disease progression or death (up to maximum observation time of 59.7 months)	No
Secondary	Number of Participants With Event-Free Survival (EFS) Event (Disease Progression, Death, or Initiation of a New Anti-Lymphoma Therapy), According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population		Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 79.5 months)	No
Secondary	Number of Participants With EFS Event (Disease Progression, Death, or Initiation of a New Anti-Lymphoma Therapy), According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population		Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 59.7 months)	No
Secondary	EFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - Relapsed/Refractory Population		Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 79.5 months)	No
Secondary	EFS, According to 2007 Revised Response Criteria for Non Hodgkin's lymphoma - First-line Population		Baseline up to disease progression or death or new anti-lymphoma treatment (up to maximum observation time of 79.5 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) - Relapsed/Refractory Population		Day 1 (Pre-infusion [0 hour {hr}], end of infusion [EOI, approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: AUClast - First-line Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: Maximum Observed Plasma Concentration (Cmax) - Relapsed/Refractory Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: Cmax - First-line Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: Systemic Clearance at Steady State (CLss) - Relapsed/Refractory Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: CLss - First-line Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: AUC From Time Zero to 7 Days (AUC7d) - Relapsed/Refractory Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: AUC7d - First-line Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: Volume of Distribution at Steady State (Vss) - Relapsed/Refractory Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: Vss - First-line Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: Plasma Half-life (t1/2) - Relapsed/Refractory Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: t1/2 - First-line Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: Plasma Trough Concentration (Ctrough) - Relapsed/Refractory Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 21 or 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacokinetics of Obinutuzumab: Ctrough - First-line Population		Day 1 (Pre-infusion [0 hr], EOI [approximately 6 hr], 3-6 hr post-infusion), Day 8 (Pre-infusion [0 hr], EOI) of Cycle 1 (1 Cycle = 28 days); end of induction (28 days after last infusion) (up to 28 months)	No
Secondary	Pharmacodynamics of Obinutuzumab: Number of Participants With Peripheral Blood B-cell Depletion - Relapsed/Refractory Population		Cycle 1 Day 1 up to end of treatment (up to the maximum observation time of 79.5 months)	No
Secondary	Pharmacodynamics of Obinutuzumab: Number of Participants With Peripheral Blood B-cell Depletion - First-line Population		Cycle 1 Day 1 up to end of treatment (up to the maximum observation time of 59.7 months)	No
Secondary	Pharmacodynamics of Obinutuzumab: Time From End of Treatment to B-Cell Recovery - Relapsed/Refractory Population		From end of treatment to B-cell recovery (up to the maximum observation time of 79.5 months)	No
Secondary	Pharmacodynamics of Obinutuzumab: Time From End of Treatment to B-Cell Recovery - First-line Population		From end of treatment to B-cell recovery (up to the maximum observation time of 59.7 months)	No