Trial from ClinicalTrials.gov

For full trial details, please see the original record at



Trial ID
NCT02329847
Ethics application status
Date submitted
30/12/2014
Date registered
30/12/2014
Date last updated
12/10/2017

Titles & IDs
Public title
A Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of the Combination of Ibrutinib With Nivolumab in Participants With Hematologic Malignancies
Scientific title
A Phase 1/2a Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of the Combination of Ibrutinib With Nivolumab in Subjects With Hematologic Malignancies
Secondary ID [1] 0 0
PCI-32765LYM1002
Secondary ID [2] 0 0
CR106681
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hematologic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: drugs - Ibrutinib
Treatment: drugs - Nivolumab

Experimental: Cohort A1 - Participants will receive ibrutinib 420 milligram (mg) capsule orally once daily and nivolumab intravenously as 3 milligram/kilogram (mg/kg) every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.

Experimental: Cohort A2 - Participants will receive ibrutinib 560 mg capsule orally once daily and nivolumab intravenously as 3 mg/kg every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.

Experimental: Cohort B1 - Participants will receive ibrutinib recommended Phase 2 dose (RP2D) orally once daily and nivolumab intravenously as 3 mg/kg every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.

Experimental: Cohort B2 - Participants will receive ibrutinib recommended Phase 2 dose (RP2D) orally once daily and nivolumab intravenously as 3 mg/kg every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.

Experimental: Cohort B3 - Participants will receive ibrutinib recommended Phase 2 dose (RP2D) orally once daily and nivolumab intravenously as 3 mg/kg every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.

Experimental: Cohort B4 - Participants will receive ibrutinib recommended Phase 2 dose (RP2D) orally once daily and nivolumab intravenously as 3 mg/kg every 2 weeks for 14-daily dosing cycles and will be continued until disease progression or unacceptable toxicity.


Treatment: drugs: Ibrutinib
Participants will receive oral capsule of ibrutinib once daily as either 420 mg or 560 mg or at recommended Phase 2 dose in any of the cohort.

Treatment: drugs: Nivolumab
Participants will receive nivolumab intravenously as 3 mg/kg on Day 1 every cycle of 14 days.

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

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) - An AE was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Timepoint [1] 0 0
2 years
Secondary outcome [1] 0 0
Overall Response Rate (ORR) - ORR is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 or the Lugano Classification by Cheson 2014 over the course of the study.
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
Duration of Stable Disease - Duration of stable disease is measured from the start of the treatment until the criteria for progression are met. Stable disease: not meeting criteria for complete response (CR), Complete Response with an Incomplete Marrow Recovery (Cri), Nodular Partial Response (nPR), Partial Response (PR), or progressive disease (PD).
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Duration of response - Duration of response will be calculated from the date of initial documentation of a response (CR, or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death. participants who are progression-free and alive or have unknown status will be censored at the last tumor assessment.
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
Progression-Free Survival (PFS) - PFS is defined as the duration from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first. Participants who are progression-free and alive or have unknown status will be censored at the last tumor assessment.
Timepoint [4] 0 0
From the date of first dose of study drug until disease progression or death, whichever occurred first, as assessed up to the last efficacy assessment for disease progression (approximately 2 years)
Secondary outcome [5] 0 0
Overall survival - Overall survival is defined as the time interval in days between the date of first dose of study drug and the participant's death from any cause.
Timepoint [5] 0 0
From the date of first dose of study drug until disease progression or death, whichever occurred first, as assessed up to the last efficacy assessment for disease progression (approximately 2 years)
Secondary outcome [6] 0 0
1-year Progression-Free Survival (PFS) Rate - The 1-year PFS rate is defined as the percentage of participants surviving 1 year after first dose of study drug without disease progression or death.
Timepoint [6] 0 0
1 year
Secondary outcome [7] 0 0
Plasma and serum concentration of Ibrutinib and nivolumab
Timepoint [7] 0 0
2 years

Eligibility
Key inclusion criteria
- Eastern Cooperative Oncology Group (ECOG) performance status grade 0, 1, or 2

- Adequate bone marrow, liver, and renal function defined as: 1) Absolute neutrophil
count (ANC) greater than equal to (>=) 1.5* 10^9cells/litre (L); 2) Platelets >=75 x
109cells/L without transfusion support within 7 days prior to test; 3) Hemoglobin >= 8
gram/deciliter (g/dL) without transfusion support within 7 days prior to test 4)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than equal to
(<=) 2.5 * upper limit of normal (ULN) 5) Total bilirubin less than (<) 2
milligram/deciliter (mg/dL) 6) Creatinine determined by serum creatinine levels <=1.5
* ULN or a calculated creatinine clearance of >= 50 mL/min/1.73 m^2

- Histologically confirmed B-cell non-Hodgkin lymphoma (B-NHL), Chronic Lymphocytic
Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

- Relapsed refractory disease after at least 1 but not more than 4 lines of previous
systemic therapy

- Measurable disease (NHL: At least 1 measurable site of disease [>1.5 centimeter [cm]
in the long axis regardless of short axis measurement or >1.0 cm in the short axis
regardless of long axis measurement, and clearly measurable in 2 perpendicular
dimensions])

- Cohort B-1: SLL/CLL: 1) Deletion of short arm of chromosome 17 or 11 q based on
institutional assessment 2) Relapsed/refractory after at least 1 prior systemic
therapy 3) Active disease based in IWCLL criteria

- Cohort B-2: 1) B- cell follicular lymphoma Grade 1, 2, or 3a (WHO criteria) 2)
Relapsed/refractory disease >= 2 lines separated by Progression, prior treatment (or
not eligible for receiving) CD20 antibody 3) Measurable disease (IWG -Lugano 2014)

- Cohort B-3: 1) Histologically-confirmed DLBCL 2) Prior standard rituximab +
anthracyclin containing regimen, received or not eligible or considered candidate of
HD-ASCT 3) Measurable disease (IWG -Lugano 2014)

- Cohort B-4: 1) Histologically-confirmed Richter syndrome defined as transformation of
CLL or SLL into an aggressive lymphoma 2) Previously treated with at least one line of
standard, systemic chemotherapy or not eligible for standard therapy 3) At least 1
measurable site of disease based on the Revised Response Criteria for Malignant
Lymphoma
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior therapy or surgery (3 to 10 weeks depending type)

- Prior BTK inhibitor or anti PD1, anti PDL1, anti PD-L2 and anti-CD137, anti-cytotoxic
T-lymphocyte associated antigen (CTLA-4) antibody

- Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by
the New York Heart Association Functional Classification, or congenital long QT
syndrome, or QT interval corrected for heart rate, using Fridericia formula (QTcF) at
Screening greater than (>) 470 milliseconds (ms)

- History of stroke or intracranial hemorrhage within 6 months prior to the first dose
of ibrutinib

- Requires treatment with anticoagulation with warfarin or equivalent vitamin K
antagonists

- Requires treatment with strong cytochrome P450 3A (CYP3A) inhibitors

- Known history of Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C

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
Blinded (masking 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
Recruiting
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
Current
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 0 0
St. Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
Israel
State/province [4] 0 0
Haifa
Country [5] 0 0
Israel
State/province [5] 0 0
Jeursalem
Country [6] 0 0
Israel
State/province [6] 0 0
Ramat Gan
Country [7] 0 0
Israel
State/province [7] 0 0
Tel Aviv
Country [8] 0 0
Poland
State/province [8] 0 0
Chorzow
Country [9] 0 0
Poland
State/province [9] 0 0
Gdansk
Country [10] 0 0
Poland
State/province [10] 0 0
Krakow
Country [11] 0 0
Poland
State/province [11] 0 0
Wroclaw
Country [12] 0 0
Spain
State/province [12] 0 0
Barcelona
Country [13] 0 0
Spain
State/province [13] 0 0
Madrid
Country [14] 0 0
Spain
State/province [14] 0 0
Salamanca
Country [15] 0 0
Turkey
State/province [15] 0 0
Ankara
Country [16] 0 0
Turkey
State/province [16] 0 0
Istanbul
Country [17] 0 0
Turkey
State/province [17] 0 0
Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the safety and to establish the recommended phase 2
dose (RP2D) for the combination of ibrutinib and nivolumab in participants with chronic
lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), follicular cell lymphoma (FL)
and diffuse large B-cell lymphoma (DLBCL). Once the dose is optimized, the combination will
be assessed for Pharmacokinetics, Pharmacodynamics, and preliminary efficacy, further safety
in participants with CLL/SLL, FL or DLBCL and in participants with Richter syndrome.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
JNJ.CT@sylogent.com
Contact person for scientific queries
Contact person responsible for updating information