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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01889186




Registration number
NCT01889186
Ethics application status
Date submitted
26/06/2013
Date registered
28/06/2013

Titles & IDs
Public title
A Study of the Efficacy of ABT-199 in Subjects With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia With the 17p Deletion
Scientific title
A Phase 2 Open-Label Study of the Efficacy of ABT-199 (GDC-0199) in Subjects With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia Harboring the 17p Deletion
Secondary ID [1] 0 0
2012-004027-20
Secondary ID [2] 0 0
M13-982
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
17p Deletion 0 0
Cancer of the Blood and Bone Marrow 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - ABT-199 (Main Cohort)
Treatment: Drugs - ABT-199 (Safety Expansion Cohort)

Experimental: Main Cohort - Participants received ABT-199 tablets once daily (QD) orally for up to 79 months. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.

Experimental: Safety Expansion Cohort - Participants received ABT-199 tablets once daily (QD) orally for up to 68 months. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.


Treatment: Drugs: ABT-199 (Main Cohort)
Participants received a test dose of ABT-199 of = 20 mg on Week 1 Day 1 of the Lead-In Period. For those with significant electrolyte and/or lymphocyte changes within 24 hours of the first dose, the 20 mg dose was maintained for 7 days with escalation to 50 mg on Week 2 Day 1. If none of the electrolyte and/or lymphocyte changes occurred within 24 hours from ABT-199 20 mg dose administration, the participant was dose-escalated to 50 mg on Week 1 Day 2. After the first dose of 50 mg, if no laboratory abnormalities occurred, the participant remained on the 50 mg dose through Week 1. After receiving the 50 mg dose for approximately 1 week (6 to 7 days), the following dose escalation proceeded with weekly increases in dose: ? 100 mg ? 200 mg ? 400 mg (or additional lead-in steps to designated 400 mg dose), as tolerated.

Treatment: Drugs: ABT-199 (Safety Expansion Cohort)
Participants received an initial dose of ABT-199 of 20 mg on Week 1 Day 1 of the Lead-In Period. If one or more electrolyte changes (from the 0 hr measurement prior to dosing) suggestive of laboratory tumor lysis syndrome (LTLS) or clinical TLS (CTLS) occurred within 24 hours of the 20 mg dose, no additional doses were administered until resolution. Upon resolution of laboratory abnormalities, the 20 mg dose was continued through Week 1. If no significant findings suggestive of clinical or laboratory TLS occurred within 24 hours, the 20 mg dose was continued through Week 1 Day 7, and escalated to a dose of 50 mg on Week 2 Day 1. Those who had drug interruptions may have been allowed to escalate to and be maintained at 50 mg for 1 week after they had been on a 20 mg dose for at least 1 week (5 - 7 days). After a week at 50 mg, weekly dose escalations were implemented as follows: 100 mg ? 200 mg ? 400 mg (or additional lead-in steps to designated 400 mg dose) as tolerated.

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

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (Main Cohort)
Timepoint [1] 0 0
Up to 36 weeks
Primary outcome [2] 0 0
Number of Participants With Adverse Events (Safety Expansion Cohort)
Timepoint [2] 0 0
From the first dose of study drug until 30 days following last dose of study drug (up to 69 months)
Secondary outcome [1] 0 0
Overall Response Rate (ORR) (Safety Expansion Cohort)
Timepoint [1] 0 0
Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Secondary outcome [2] 0 0
Complete Remission (CR) Rate
Timepoint [2] 0 0
Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Secondary outcome [3] 0 0
Partial Remission (PR) Rate
Timepoint [3] 0 0
Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Secondary outcome [4] 0 0
Duration of Overall Response
Timepoint [4] 0 0
Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Secondary outcome [5] 0 0
Progression-free Survival
Timepoint [5] 0 0
Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Secondary outcome [6] 0 0
Event-free Survival
Timepoint [6] 0 0
Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Secondary outcome [7] 0 0
Time to Progression
Timepoint [7] 0 0
Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Secondary outcome [8] 0 0
Time to First Response
Timepoint [8] 0 0
Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Secondary outcome [9] 0 0
Time to 50% Reduction in Absolute Lymphocyte Count
Timepoint [9] 0 0
Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Secondary outcome [10] 0 0
Overall Survival
Timepoint [10] 0 0
Up to the data cutoff date of 15 December 2020, approximately 7.5 years of follow-up
Secondary outcome [11] 0 0
Percentage of Participants Who Moved on to Stem Cell Transplant
Timepoint [11] 0 0
Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Eligibility
Key inclusion criteria
* Participant must be greater than or equal to 18 years of age.
* Participant must have diagnosis of chronic lymphocytic leukemia (CLL) that meets published 2008 Modified IWCLL NCI-WG (International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute-Working Group) Guidelines.

* Participant has an indication for treatment according to the 2008 Modified IWCLL NCI WG Guidelines;
* Participant has clinically measurable disease (lymphocytosis > 5 × 10^9/L and/or palpable and measurable nodes by physical exam and/or organomegaly assessed by physical exam);
* Participant must be refractory or have relapsed after receiving at least one prior line of therapy (participants that have progressed after 1 cycle of treatment or have completed at least 2 cycles of treatment for a given line of therapy) or previously untreated CLL (previously untreated CLL participants must have received no prior chemotherapy or immunotherapy. Participants with a history of emergency, loco-regional radiotherapy (e.g., for relief of compressive signs or symptoms) are eligible. In addition, participants must meet the CLL diagnostic criteria above and must have > 5 × 10^9/L B-Lymphocytes in the peripheral blood.);
* Participants must have 17p deletion, assessed by local laboratory (in bone marrow or peripheral blood) or assessed by central laboratory (peripheral blood).
* Participant has an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
* Participant must have adequate bone marrow function at Screening as follows:

* Absolute Neutrophil Count (ANC) greater than or equal to 1000/µL, or
* For subjects with an ANC less than 1000/µL at Screening and bone marrow heavily infiltrated with underlying disease (unless cytopenia is clearly due to marrow involvement of CLL), growth factor support may be administered after Screening and prior to the first dose of ABT-199 to achieve the ANC eligibility criteria (greater than or equal to 1000/µL);
* Platelets greater than 30,000/mm^3 (without transfusion support within 14 days of Screening, without evidence of mucosal bleeding, without known history of bleeding episode within 3 months of Screening, and without history of bleeding disorder);
* Hemoglobin greater than or equal to 8.0 g/dL.
* Participant must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening as follows:

* Activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5 × the upper limit of normal;
* Calculated creatinine clearance greater than 50 mL/min using 24-hour Creatinine Clearance or modified Cockcroft-Gault equation (using Ideal Body Mass [IBM] instead of Mass). For participants that have body mass index (BMI) of > 30 kg/m^2 or < 19 kg/m^2, 24-hour measured urine creatinine clearance is required;
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3.0 × the upper normal limit of institution's normal range; Bilirubin less than or equal to 1.5 × upper limit of normal. Participants with Gilbert's Syndrome may have a bilirubin greater 1.5 × upper limit of normal, per correspondence between the investigator and AbbVie medical monitor.
* For participants at high risk of tumor lysis syndrome a pre-approval by the AbbVie medical monitor is required prior to enrollment.
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participant has undergone an allogeneic stem cell transplant.
* Participant has developed Richter's transformation confirmed by biopsy.
* Participant has prolymphocytic leukemia.
* Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to Screening), including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura despite low dose corticosteroids.
* Participant has previously received ABT-199.
* Participant has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.
* Participant has received any of the following within 14 days or 5 half-lives as applicable prior to the first dose of study drug, or has not recovered to less than Common Toxicity Criteria (CTC) grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:

* Any anti-cancer therapy including chemotherapy, or radiotherapy;
* Investigational therapy, including targeted small molecule agents.
* Participant has known allergy to both xanthine oxidase inhibitors and rasburicase.

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
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
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,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital /ID# 98836 - St Leonards
Recruitment hospital [2] 0 0
John Fawkner Private Hospital /ID# 98835 - Coburg
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Ctr /ID# 91795 - Melbourne
Recruitment hospital [4] 0 0
Royal Melbourne Hospital /ID# 91794 - Parkville
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
3058 - Coburg
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Parkville
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
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
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
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
France
State/province [12] 0 0
Auvergne-Rhone-Alpes
Country [13] 0 0
France
State/province [13] 0 0
Ile-de-France
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
France
State/province [15] 0 0
Rouen
Country [16] 0 0
Germany
State/province [16] 0 0
Baden-Wuerttemberg
Country [17] 0 0
Germany
State/province [17] 0 0
Nordrhein-Westfalen
Country [18] 0 0
Germany
State/province [18] 0 0
Schleswig-Holstein
Country [19] 0 0
Germany
State/province [19] 0 0
Thueringen
Country [20] 0 0
Germany
State/province [20] 0 0
Dresden
Country [21] 0 0
Germany
State/province [21] 0 0
Freiburg
Country [22] 0 0
Germany
State/province [22] 0 0
Göttingen
Country [23] 0 0
Germany
State/province [23] 0 0
Mainz
Country [24] 0 0
Germany
State/province [24] 0 0
Muenchen
Country [25] 0 0
Poland
State/province [25] 0 0
Lubelskie
Country [26] 0 0
Poland
State/province [26] 0 0
Malopolskie
Country [27] 0 0
Poland
State/province [27] 0 0
Opolskie
Country [28] 0 0
United Kingdom
State/province [28] 0 0
England
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Bournemouth
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Cambridge
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Leeds
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Liverpool
Country [33] 0 0
United Kingdom
State/province [33] 0 0
London
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Manchester
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Oxford
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Plymouth
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Available to whom?
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.