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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02624986




Registration number
NCT02624986
Ethics application status
Date submitted
1/12/2015
Date registered
9/12/2015
Date last updated
18/05/2020

Titles & IDs
Public title
A Study of Idasanutlin in Combination With Obinutuzumab in Relapsed/Refractory (R/R) Follicular Lymphoma (FL) and in Combination With Rituximab in R/R Diffuse Large B-Cell Lymphoma (DLBCL) Participants
Scientific title
A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Idasanutlin in Patients With Relapsed or Refractory Follicular Lymphoma and Obinutuzumab or Rituximab in Combination With Idasanutlin in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
Secondary ID [1] 0 0
2015-002100-83
Secondary ID [2] 0 0
BH29812
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin's Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Idasanutlin
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Rituximab

Experimental: DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg - Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 100 milligrams (mg) orally in combination with a fixed dose of obinutuzumab 1000 mg intravenously (IV) for 6 cycles (1 cycle = 28 days).

Experimental: DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg - Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).

Experimental: DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg - Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 200 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).

Experimental: DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2 - Participants with diffuse large B-cell lymphoma (DLBCL) in this bridging cohort received induction treatment with idasanutlin 150 mg orally in combination with rituximab 375 milligrams per square meter of body surface area (mg/m\^2) IV for 6 cycles (1 cycle = 28 days).

Experimental: DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2 - Participants with diffuse large B-cell lymphoma (DLBCL) in this bridging cohort received induction treatment with idasanutlin 200 mg orally in combination with rituximab 375 mg/m\^2 IV for 6 cycles (1 cycle = 28 days).

Experimental: FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg - Participants with follicular lymphoma (FL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 100 milligrams (mg) orally in combination with a fixed dose of obinutuzumab 1000 mg intravenously (IV) for 6 cycles (1 cycle = 28 days).

Experimental: FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg - Participants with follicular lymphoma (FL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).

Experimental: FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg - Participants with follicular lymphoma (FL) in this bridging cohort received induction treatment with single-agent obinutuzumab 1000 mg IV for Cycle 1 and then idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for Cycles 2-6 (1 cycle = 28 days).


Treatment: Drugs: Idasanutlin
Participants received idasanutlin film-coated tablets orally at a starting dose of 100 mg daily on Days 1 to 5 of each 28-day cycle. Escalation was to occur in at least 50-mg increments, and daily doses greater than or equal to (=) 400 mg will be split into twice daily dosing.

Treatment: Drugs: Obinutuzumab
Participants received a fixed dose of obinutuzumab 1000 mg intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 (1 cycle = 28 days). For eligible participants with FL, post-induction treatment was to be given at a dose of 1000 mg via IV infusion on Day 1 once every 2 months for a maximum of up to 24 months.

Treatment: Drugs: Rituximab
Participants received a fixed dose of rituximab, 375 mg/m\^2 IV infusion on Day 1 of Cycles 1-6. Post-induction treatment for eligible participants was to be given at a dose of 375 mg/m\^2 IV infusion on Day 1 of every other month for up to 6 months, until disease progression or unacceptable toxicity.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Complete Response at the End of Induction, Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scans Using Modified Lugano 2014 Criteria
Timepoint [1] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Secondary outcome [1] 0 0
Number of Participants With a Dose-Limiting Toxicity
Timepoint [1] 0 0
Cycles 1, 2 (1 cycle is 28 days)
Secondary outcome [2] 0 0
Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
Timepoint [2] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Secondary outcome [3] 0 0
Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using Lugano 2014 Criteria
Timepoint [3] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Secondary outcome [4] 0 0
Percentage of Participants With Complete Response at the End of Induction, Determined by the IRC on the Basis of CT Scans Alone Using Lugano 2014 Criteria
Timepoint [4] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Secondary outcome [5] 0 0
Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of CT Scans Alone Using Lugano 2014 Criteria
Timepoint [5] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Secondary outcome [6] 0 0
Percentage of Participants With Objective Response at the End of Induction, Determined by the IRC on the Basis of PET-CT Scans Using Lugano 2014 Criteria
Timepoint [6] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Secondary outcome [7] 0 0
Percentage of Participants With Objective Response at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using Lugano 2014 Criteria
Timepoint [7] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Secondary outcome [8] 0 0
Percentage of Participants With Objective Response at the End of Induction, Determined by an IRC on the Basis of CT Scans Alone Using Lugano 2014 Criteria
Timepoint [8] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Secondary outcome [9] 0 0
Percentage of Participants With Objective Response at the End of Induction, Determined by the Investigator on the Basis of CT Scans Alone Using Lugano 2014 Criteria
Timepoint [9] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Secondary outcome [10] 0 0
Percentage of Participants With Best Response of Complete Response or Partial Response During the Study, Determined by the Investigator on the Basis of CT Scans Alone Using Lugano 2014 Criteria
Timepoint [10] 0 0
Baseline, Cycle 2, end of induction (up to 6 cycles; 1 cycle is 28 days), every 2 months (FL) until end of maintenance or at 4 months (DLBCL) of consolidation treatment, and then every 6 months during follow-up until disease progression (up to 3.5 years)
Secondary outcome [11] 0 0
Plasma Idasanutlin Concentrations in DLBCL and FL Participants at Nominal Sampling Timepoints Grouped by Idasanutlin Dose and Combination Partner (Obinutuzumab or Rituximab)
Timepoint [11] 0 0
Predose (0 hours) and 6 hours postdose on Day 1 of Cycles 1, 2, and 4; Predose (0 hours) and 2, 4, 6, and 24 hours postdose on Day 5 of Cycles 1 and 2; Predose (0 hours) and 6 and 24 hours postdose on Cycle 4, Day 5 (1 cycle is 28 days)
Secondary outcome [12] 0 0
Serum Obinutuzumab Concentrations in DLBCL and FL Participants at Nominal Sampling Timepoints
Timepoint [12] 0 0
Pre-infusion (0 hour) and 0.5 hours after end of obinutuzumab infusion on Day 1 of Cycles 1, 2, 4, and 6
Secondary outcome [13] 0 0
Serum Rituximab Concentrations in DLBCL Participants at Nominal Sampling Timepoints
Timepoint [13] 0 0
Pre-infusion (0 hours) at Cycle 1, Day 1 and Cycle 2, Day 1; Post-infusion 0.5 hours at Cycle 1, Day 1 (1 cycle is 28 days)
Secondary outcome [14] 0 0
Safety Summary of the Number of Participants With at Least One Adverse Event by Type and Severity According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)
Timepoint [14] 0 0
From first dose until 90 days after the last dose of study drug treatment (up to 31 months)
Secondary outcome [15] 0 0
Baseline Value and Change From Baseline Values of Systolic Blood Pressure at Specified Timepoints
Timepoint [15] 0 0
Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Secondary outcome [16] 0 0
Baseline Value and Change From Baseline Values of Diastolic Blood Pressure at Specified Timepoints
Timepoint [16] 0 0
Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Secondary outcome [17] 0 0
Baseline Value and Change From Baseline Values of Pulse Rate at Specified Timepoints
Timepoint [17] 0 0
Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Secondary outcome [18] 0 0
Baseline Value and Change From Baseline Values of Respiratory Rate at Specified Timepoints
Timepoint [18] 0 0
Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Secondary outcome [19] 0 0
Baseline Value and Change From Baseline Values of Body Temperature at Specified Timepoints
Timepoint [19] 0 0
Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Secondary outcome [20] 0 0
Number of Participants by Electrocardiogram (ECG) Results Assessment Shift From Baseline to Specified Post-Baseline Timepoints
Timepoint [20] 0 0
Baseline, Induction Cycle 1 Day 1 and Cycle 4 Day 1, End of Induction (up to 6 cycles; 1 cycle is 28 days); Every 2 months during maintenance treatment from Months 1-23; End of Maintenance (up to 24 months); Unscheduled Visits (as clinically indicated)
Secondary outcome [21] 0 0
Hematology Laboratory Test Results Shift Table: Number of Participants by Highest NCI-CTCAE v4.0 Grade at Baseline to Highest Grade Post-Baseline
Timepoint [21] 0 0
From Baseline until 35 days after the last dose of study drug (up to 29 months)
Secondary outcome [22] 0 0
Blood Chemistry Laboratory Test Results Shift Table: Number of Participants by Highest NCI-CTCAE v4.0 Grade at Baseline to Highest Grade Post-Baseline
Timepoint [22] 0 0
From Baseline until 35 days after the last dose of study drug (up to 29 months)

Eligibility
Key inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Histologically documented cluster of differentiation (CD) 20-positive B-cell lymphoma classified as relapsed or refractory FL or DLBCL after treatment with at least two prior chemoimmunotherapy regimens that included an anti-CD20 monoclonal antibody (mAb) and for which no other more appropriate treatment option exists
* At least one bidimensionally measurable lesion
* Agreement to remain abstinent or use adequate contraception, among women or men of childbearing potential
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known CD20-negative status at relapse or progression
* Prior allogeneic stem cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1
* Current use of systemic corticosteroids greater than (>) 20 mg prednisone per day (or equivalent), or prior anti-cancer therapy to include: radioimmunoconjugate within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1
* Requirement for chronic anticoagulation
* Central nervous system (CNS) disease
* Active infection
* Positive for human immunodeficiency virus (HIV) or hepatitis B or C
* Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1
* Poor hematologic, renal, or hepatic function
* Pregnant or lactating women
* History of progressive multifocal leukoencephalopathy (PML)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Linear Clinical Research Limited - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Rhode Island
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
Germany
State/province [8] 0 0
Augsburg
Country [9] 0 0
Germany
State/province [9] 0 0
Berlin
Country [10] 0 0
Germany
State/province [10] 0 0
Heilbronn
Country [11] 0 0
Germany
State/province [11] 0 0
Köln
Country [12] 0 0
Germany
State/province [12] 0 0
Würzburg
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Daegu
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Gyeonggi-do
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul
Country [16] 0 0
New Zealand
State/province [16] 0 0
Auckland
Country [17] 0 0
New Zealand
State/province [17] 0 0
Christchurch
Country [18] 0 0
New Zealand
State/province [18] 0 0
Grafton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.