Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01779791




Registration number
NCT01779791
Ethics application status
Date submitted
25/01/2013
Date registered
30/01/2013
Date last updated
18/07/2017

Titles & IDs
Public title
A Study of PCI-32765 (Ibrutinib) in Patients With Refractory Follicular Lymphoma
Scientific title
An Open-Label, Multicenter, Single-Arm, Phase 2 Study of PCI-32765 (Ibrutinib) in Subjects With Refractory Follicular Lymphoma
Secondary ID [1] 0 0
2012-004097-26
Secondary ID [2] 0 0
CR100956
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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 - PCI-32765 (Ibrutinib)

Experimental: PCI-32765 (Ibrutinib) -


Treatment: Drugs: PCI-32765 (Ibrutinib)
560 mg capsules administered orally once daily, continuously on a 21-day cycle until progressive disease.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall response rate
Timepoint [1] 0 0
Up to 2 years after the last patient is enrolled
Secondary outcome [1] 0 0
Duration of response
Timepoint [1] 0 0
Every 12 weeks during the first 96 weeks, followed by every 24 weeks thereafter until disease progression (up to 2 years after the last patient is enrolled)
Secondary outcome [2] 0 0
Progression-free survival
Timepoint [2] 0 0
Up to progressive disease, death, lost to follow-up, withdrawal of consent, or study end (up to 2 years after the last patient is enrolled)
Secondary outcome [3] 0 0
Overall survival
Timepoint [3] 0 0
Up to death, lost to follow-up, withdrawal of consent, or study end (up to 2 years after the last patient is enrolled)
Secondary outcome [4] 0 0
Time to response
Timepoint [4] 0 0
Every 12 weeks during the first 96 weeks, followed by every 24 weeks thereafter until disease progression (up to 2 years after the last patient is enrolled)
Secondary outcome [5] 0 0
Number of patients experiencing resolution of lymphoma-related B symptoms
Timepoint [5] 0 0
Day 1 of every cycle during the first 12 months, thereafter every other cycle (up to 2 years after the last patient is enrolled)
Secondary outcome [6] 0 0
Number of patients identified with blood biomarkers that alter B-cell receptor signaling or activate alternative signaling pathways
Timepoint [6] 0 0
Day 1 of Cycles 1-3, and time of disease progression, or at end-of treatment visit for patients who discontinue treatment without disease progression
Secondary outcome [7] 0 0
Minimum plasma concentration of PCI-32765
Timepoint [7] 0 0
Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
Secondary outcome [8] 0 0
Oral plasma clearance of PCI-32765
Timepoint [8] 0 0
Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
Secondary outcome [9] 0 0
Oral volume of distribution at steady state of PCI-32765
Timepoint [9] 0 0
Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
Secondary outcome [10] 0 0
Area under the plasma-concentration time curve of PCI-32765
Timepoint [10] 0 0
Pre-dose Day 1 of Cycles 1-3, post-dose Day 1 of Cycles 1, 2 at 1, 2, and 4 hours
Secondary outcome [11] 0 0
Number of participants affected by an adverse event
Timepoint [11] 0 0
Up to 30 days after the last dose of study medication

Eligibility
Key inclusion criteria
* Histologic proof of Grade 1, 2, or 3a follicular lymphoma (FL) without clinical or pathological evidence of transformation
* Previously treated with at least 2 prior lines of therapy, including at least 1 rituximab combination chemotherapy regimen; last prior line of therapy includes an anti CD20 monoclonal antibody-containing chemotherapy regimen (separate lines of therapy are defined as different regimens that are either separated by disease progression, refractory disease, or relapsed disease)
* Resistant disease to the last therapy, defined as progression of disease during or within 12 months of the last dose of chemotherapy in a CD20 antibody combination chemotherapy regimen
* At least 1 measurable site of disease according to International Working Group Revised Response Criteria for Malignant Lymphoma
* Eastern Cooperative Oncology Group performance status grade 0 or 1
* Hematology and biochemical laboratory values must be within protocol-defined parameters within 7 days prior to enrollment
* Agrees to protocol-defined use of effective contraception
* Women of childbearing potential must have a negative serum or urine pregnancy test at screening
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of first dose of study drug
* Prior treatment with PCI-32765 or other Bruton's tyrosine kinase inhibitors (patients who progressed or became refractory while on treatment with PI3K inhibitors are excluded)
* Concurrent enrollment in another therapeutic investigational clinical treatment study
* Received a prior allogeneic hematopoietic stem cell transplant (prior autologous hematopoietic stem cell transplant is allowed)
* Known central nervous system lymphoma
* History of prior malignancy (except malignancy treated with curative intent and with no known active disease present for >=3 years before enrollment, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, or adequately treated cervical carcinoma in situ without evidence of disease)
* History of stroke or intracranial hemorrhage within 6 months prior to enrollment
* Requires anticoagulation with warfarin or equivalent vitamin K antagonists
* Requires treatment with strong cytochrome P450 (CYP)3A4/5 inhibitors
* 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
* Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C or active infection with Hepatitis B or any uncontrolled active systemic infection requiring intravenous antibiotics
* Women who are pregnant or breastfeeding
* Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of PCI-32765 capsules, or put the study outcomes at undue risk

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/04/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/05/2016
Sample size
Target
Accrual to date
Final
110
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Concord
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- Milton
Recruitment hospital [5] 0 0
- Prahran
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Concord
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Milton
Recruitment postcode(s) [5] 0 0
- Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Vermont
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Belgium
State/province [17] 0 0
Courrière
Country [18] 0 0
Belgium
State/province [18] 0 0
Gent
Country [19] 0 0
Belgium
State/province [19] 0 0
Leuven
Country [20] 0 0
France
State/province [20] 0 0
Creteil
Country [21] 0 0
France
State/province [21] 0 0
Nice Cedex 2
Country [22] 0 0
France
State/province [22] 0 0
Nimes Cedex 9
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Pessac
Country [25] 0 0
France
State/province [25] 0 0
Pierre Benite
Country [26] 0 0
France
State/province [26] 0 0
Rennes
Country [27] 0 0
Germany
State/province [27] 0 0
Heidelberg
Country [28] 0 0
Germany
State/province [28] 0 0
Köln
Country [29] 0 0
Germany
State/province [29] 0 0
Mainz
Country [30] 0 0
Germany
State/province [30] 0 0
Ulm
Country [31] 0 0
Poland
State/province [31] 0 0
Krakow
Country [32] 0 0
Poland
State/province [32] 0 0
Warszawa
Country [33] 0 0
Poland
State/province [33] 0 0
Wroclaw
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Ekaterinburg
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Moscow N/A
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Nizhny Novgorod
Country [37] 0 0
Russian Federation
State/province [37] 0 0
St-Petersburg
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Volgograd
Country [39] 0 0
Spain
State/province [39] 0 0
Barcelona
Country [40] 0 0
Spain
State/province [40] 0 0
Marbella
Country [41] 0 0
Spain
State/province [41] 0 0
Salamanca
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Liverpool
Country [43] 0 0
United Kingdom
State/province [43] 0 0
London
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Manchester
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Southampton

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
Pharmacyclics LLC.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy and safety of PCI-32765 (ibrutinib) administered to patients with chemoimmunotherapy-resistant follicular lymphoma (FL).
Trial website
https://clinicaltrials.gov/study/NCT01779791
Trial related presentations / publications
Balasubramanian S, Hodkinson B, Schuster SJ, Fowler NH, Trotman J, Hess G, Cheson BD, Schaffer M, Sun S, Deshpande S, Vermeulen J, Salles G, Gopal AK. Identification of a genetic signature enriching for response to ibrutinib in relapsed/refractory follicular lymphoma in the DAWN phase 2 trial. Cancer Med. 2022 Jan;11(1):61-73. doi: 10.1002/cam4.4422. Epub 2021 Nov 17.
Gopal AK, Schuster SJ, Fowler NH, Trotman J, Hess G, Hou JZ, Yacoub A, Lill M, Martin P, Vitolo U, Spencer A, Radford J, Jurczak W, Morton J, Caballero D, Deshpande S, Gartenberg GJ, Wang SS, Damle RN, Schaffer M, Balasubramanian S, Vermeulen J, Cheson BD, Salles G. Ibrutinib as Treatment for Patients With Relapsed/Refractory Follicular Lymphoma: Results From the Open-Label, Multicenter, Phase II DAWN Study. J Clin Oncol. 2018 Aug 10;36(23):2405-2412. doi: 10.1200/JCO.2017.76.8853. Epub 2018 May 31.
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
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/study/NCT01779791