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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02624986
Ethics application status
Date submitted
1/12/2015
Date registered
9/12/2015
Date last updated
24/06/2019

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: Dose-Escalation Cohort (DLBCL Participants) - Participants will receive 'Regimen A', which includes escalating doses of idasanutlin in combination with a fixed dose of obinutuzumab (1000 milligrams [mg]) for 6 cycles (1 Cycle=28 days) until maximum tolerated dose (MTD) is achieved. Regimen A will be followed by treatment which includes idasanutlin in combination with fixed dose of rituximab (375 milligrams per square meter [mg/m^2]) for 6 cycles (1 Cycle=28 days) to determine the RP2D for this treatment.

Experimental: Dose-Escalation Cohort (FL Participants) - Participants will receive 'Regimen A', which includes escalating doses of idasanutlin in combination with a fixed dose of obinutuzumab (1000 mg) for 6 cycles (1 Cycle=28 days) until MTD is achieved. Regimen A will be followed by Regimen B which includes obinutuzumab given alone in Cycle 1 and idasanutlin and obinutuzumab combination from Cycles 2-6 (1 Cycle=28 days) to determine the RP2D for this regimen.

Experimental: Expansion Cohort: DLBCL Participants - Participants with DLBCL will receive 6 cycles (1 Cycle=28 days) of induction treatment with idasanutlin at the RP2D identified during the dose-escalation phase, in combination with rituximab. Induction treatment will be followed by post-induction consolidation treatment with rituximab and idasanutlin for 6 months.

Experimental: Expansion Cohort: FL Participants - Participants will receive 6 cycles (1 Cycle=28 days) of induction treatment with idasanutlin at the RP2D identified during the dose-escalation phase, in combination with obinutuzumab. Participants will receive either 'Regimen A' or 'Regimen B' which will be determined at the end of the dose-escalation phase. Induction treatment will be followed by post-induction maintenance treatment with obinutuzumab and idasanutlin for a maximum of up to 24 months.


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

Treatment: Drugs: Obinutuzumab
Participants will receive 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 may be given at a dose of 1000 mg via IV infusion on Day 1 of every other month for a maximum of up to 24 months.

Treatment: Drugs: Rituximab
Participants will receive a fixed dose of rituximab, 375 mg/m^2 IV infusion on Day 1 of Cycles 1-6. Post-induction treatment for eligible participants may 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 (CR), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans
Timepoint [1] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks from Day 1 of Cycle 1) (1 Cycle=28 days)
Secondary outcome [1] 0 0
Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Cycles 1, 2 (1 Cycle=28 days)
Secondary outcome [2] 0 0
Recommended Phase 2 Dose (RP2D) for Idasanutlin in Combination with Obinutuzumab
Timepoint [2] 0 0
Cycles 1, 2 (1 Cycle=28 days)
Secondary outcome [3] 0 0
RP2D of Idasanutlin in Combination with Rituximab
Timepoint [3] 0 0
Cycles 1, 2 (1 Cycle=28 days)
Secondary outcome [4] 0 0
Percentage of Participants with CR, Determined by the Investigator on the Basis of PET and CT Scans
Timepoint [4] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks from Day 1 of Cycle 1) (1 Cycle=28 days)
Secondary outcome [5] 0 0
Percentage of Participants with CR, Determined by an IRC and the Investigator on the Basis of CT Scans Alone
Timepoint [5] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks from Day 1 of Cycle 1) (1 Cycle=28 days)
Secondary outcome [6] 0 0
Percentage of Participants with Objective Response, Determined by an IRC on the Basis of PET and CT Scans
Timepoint [6] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks from Day 1 of Cycle 1) (1 Cycle=28 days)
Secondary outcome [7] 0 0
Percentage of Participants with Objective Response, Determined by the Investigator on the Basis of PET and CT Scans
Timepoint [7] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks from Day 1 of Cycle 1) (1 Cycle=28 days)
Secondary outcome [8] 0 0
Percentage of Participants with Objective Response, Determined by an IRC on the Basis of CT Scans Alone
Timepoint [8] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks from Day 1 of Cycle 1) (1 Cycle=28 days)
Secondary outcome [9] 0 0
Percentage of Participants with Objective Response, Determined by the Investigator on the Basis of CT Scans Alone
Timepoint [9] 0 0
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks from Day 1 of Cycle 1) (1 Cycle=28 days)
Secondary outcome [10] 0 0
Percentage of Participants with Best Response of CR or Partial Response (PR), Determined by the Investigator on the Basis of CT Scans Alone
Timepoint [10] 0 0
Baseline up to disease progression or death whichever occurs first (up to approximately 4 years)
Secondary outcome [11] 0 0
Serum Obinutuzumab Concentration - Pre-infusion (any time prior to the first dose on that day) (infusion starts at 50 milligrams per hour [mg/hr] then may be increased by 50mg/hr every 30 minutes to maximum of 400mg/hr), 30 minutes (min) after end of infusion on Day 1 Cycle 1; pre-infusion (within 5 hr prior to dose), 30 min after end of obinutuzumab infusion on Day 1 of Cycles 2, 4, 6; pre-obinutuzumab infusion (within 5 hr prior to dose) on Day 1 of months 1, 7, 13, 19; anytime during treatment discontinuation visit, 120 days after the last dose, and 1-2 years after the last dose (1 cycle=28 days) up to approximately 4 years.
Timepoint [11] 0 0
Pre-infusion (0 hours [hr]) up to approximately 4 years (Detailed time frame is available in outcome measure description)
Secondary outcome [12] 0 0
Serum Rituximab Concentration in DLBCL Participants - Pre-infusion (any time prior to the first dose on that day) (infusion starts at 50 mg/hr then may be increased by 50mg/hr every 30 minutes to maximum of 400mg/hr), 30 min after end of infusion on Day 1 Cycle 1; pre-infusion (within 5 hr prior to dose) on Day 1 of Cycles 2, 4; pre-infusion (within 5 hr prior to dose), 30 min after end of obinutuzumab infusion on Day 1 of Cycle 6 (1 cycle=28 days) up to approximately 4 years.
Timepoint [12] 0 0
Pre-infusion (0 hr) up to approximately 4 years (Detailed time frame is available in outcome measure description)
Secondary outcome [13] 0 0
Plasma Idasanutlin Concentration in DLBCL Participants - Pre-administration (any time prior the first dose that day), 6 hr post idasanutlin administration on Day 1 of Cycle 1, prior to idasanutlin administration (within 1 hr prior to dose), 2, 4, 6 hrs post-idasanutlin administration on Day 5 of Cycle 1; pre-administration (within 1 hr prior to dose), 6 hr post-idasanutlin administration on Days 1, 5 of Cycles 2, 4 up to end of induction phase of 6 cycles (1 cycle=28 days).
Timepoint [13] 0 0
Pre-administration (0 hr) up to end of induction phase of 6 cycles (1 Cycle=28 days) (Detailed time frame is available in outcome measure description)
Secondary outcome [14] 0 0
Plasma Idasanutlin Concentration in FL Participants - Pre-administration (any time prior the first dose that day), 6 hr post idasanutlin administration on Day 1 of Cycle 1, prior to idasanutlin administration (within 1 hr prior to dose), 2, 4, 6 hrs post-idasanutlin administration on Day 5 of Cycle 1; pre-administration (within 1 hr prior to dose), 6 hr post-idasanutlin administration on Days 1, 5 of Cycles 2, 4 up to end of induction phase of 6 cycles (1 cycle=28 days).
Timepoint [14] 0 0
Pre-administration (0 hr) up to end of induction phase of 6 cycles (1 Cycle=28 days) (Detailed time frame is available in outcome measure description)
Secondary outcome [15] 0 0
Percentage of Participants with Adverse Events
Timepoint [15] 0 0
Baseline up to approximately 4 years

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
Gender
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/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
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
Minnesota
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Rhode Island
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Germany
State/province [9] 0 0
Augsburg
Country [10] 0 0
Germany
State/province [10] 0 0
Berlin
Country [11] 0 0
Germany
State/province [11] 0 0
Heilbronn
Country [12] 0 0
Germany
State/province [12] 0 0
Köln
Country [13] 0 0
Germany
State/province [13] 0 0
Würzburg
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Daegu
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Gyeonggi-do
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Seoul
Country [17] 0 0
New Zealand
State/province [17] 0 0
Auckland
Country [18] 0 0
New Zealand
State/province [18] 0 0
Christchurch
Country [19] 0 0
New Zealand
State/province [19] 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
This is a open-label, mutlicenter, non-randomized, study to evaluate the safety, efficacy,
and pharmacokinetics of idasanutlin in combination with obinutuzumab in participants with R/R
FL and rituximab in combination with idasanutlin in R/R DLBCL. The study will include an
initial dose-escalation phase followed by an expansion phase. The dose-escalation phase is
designed to determine the recommended phase 2 dose (RP2D) for idasanutlin in combination with
obinutuzumab for FL and in combination with rituximab for DLBCL. The expansion phase is
designed to further assess the safety and efficacy of obinutuzumab in combination with
idasanutlin at the RP2D with the selected regimen in participants with R/R FL and of
rituximab in combination with idasanutlin at the RP2D in participants with R/R DLBCL.
Trial website
https://clinicaltrials.gov/show/NCT02624986
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sai Li, M.D., Ph.D.
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

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02624986