A Study of the Efficacy of ABT-199 in Subjects With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia With the 17p Deletion

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01889186
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 158
• Locations: 48
• Arms: 2
• Actual Duration (Months): 89.6
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This was an open-label, multicenter, global study to determine the efficacy of ABT-199 (Venetoclax) monotherapy in participants with relapsed/refractory (R/R) or previously untreated chronic lymphocytic leukemia (CLL) harboring 17p deletion.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia; 17p Deletion; Cancer of the Blood and Bone Marrow	Drug: ABT-199 (Main Cohort); Drug: ABT-199 (Safety Expansion Cohort)	Phase 2

Detailed Description

This study was designed to enroll approximately 150 participants in 2 cohorts: a main cohort of approximately 100 participants, and a safety expansion (SE) cohort of approximately 50 participants. The primary objective of the main cohort was to evaluate the efficacy of ABT-199 monotherapy in participants with R/R CLL harboring the 17p deletion. The primary objective of the safety expansion cohort was to evaluate the safety of ABT-199 in approximately 50 participants with R/R CLL harboring 17p deletion treated per updated tumor lysis syndrome (TLS) prophylaxis and management measures.

Study Design

• Study Type: Interventional
• Actual Enrollment: 158 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: Jun 27, 2013
• Actual Primary Completion Date: Oct 28, 2020
• Actual Study Completion Date: Dec 15, 2020

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: 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.; Other Names: Venetoclax GDC-0199
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.	Drug: 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.; Other Names: Venetoclax GDC-0199

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (Main Cohort) [Up to 36 weeks]

   The overall response rate (ORR) is defined as the proportion of participants with an overall response (complete remission [CR] + complete remission with incomplete marrow recovery [CRi] + nodular partial remission [nPR] + partial remission [PR]) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria as assessed by the Independent Review Committee (IRC) in the first 70 participants treated in the Main Cohort.

2. Number of Participants With Adverse Events (Safety Expansion Cohort) [From the first dose of study drug until 30 days following last dose of study drug (up to 69 months)]

   An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

Secondary Outcome Measures

1. Overall Response Rate (ORR) (Safety Expansion Cohort) [Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up]

   The overall response rate (ORR) is defined as the proportion of participants with an overall response (complete remission [CR] + complete remission with incomplete marrow recovery [CRi] + nodular partial remission [nPR] + partial remission [PR]) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria.

2. Complete Remission (CR) Rate [Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up]

   Complete remission was defined as the proportion of participants who achieved a CR or Complete Remission with Incomplete Marrow Recovery(CRi ) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria. Participants who did not achieve a CR or CRi were considered to be non-responders in the calculation of CR rate.

3. Partial Remission (PR) Rate [Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up]

   PR rate was defined as the proportion of participants who achieved a nodular partial remission (nPR) or PR per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria. Participants who did not achieve a nPR or PR were considered to be non-responders in the calculation of PR rate.

4. Duration of Overall Response [Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up]

   Duration of overall response (DoR) was defined as the number of days from the date of first response (CR, CRi, nPR, or PR) by either CT scan or physical exam determination to the earliest recurrence (progressive disease; PD) or death. For participants who had a PR before CR, CRi, or nPR in subsequent visits, the DoR was computed from the earliest PR. If a participant was still responding, then their data was censored at the date of their last available disease assessment. To be included in the DoR analysis, participants must have had a response per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria (CR, CRi, confirmed nPR, or confirmed PR). For participants who never experienced response, their data was not included in the analysis.

5. Progression-free Survival [Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up]

   Duration of progression-free survival (PFS) was defined as the number of days from the date of first dose to the date of earliest disease progression or death. All disease progression was included regardless of whether the event occurred while the participant was taking ABT-199 or had previously discontinued ABT-199. If the participant does not experience disease progression or death, then the data was censored at the date of last disease assessment. Data for participants without any disease assessments performed after the baseline visit were censored at the date of first dose plus 1 day.

6. Event-free Survival [Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up]

   Event-free survival (EFS) was defined as the number of days from the date of first dose to the date of earliest disease progression, death, or start of a new anti-leukemic therapy. If the specified event (disease progression, death, start of a new anti-leukemic treatment) did not occur, participants were censored at the date of last disease assessment. Data for participants without any disease assessments performed after the baseline visit were censored at the date of first dose plus 1 day.

7. Time to Progression [Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up]

   Time to progression (TTP) was defined as the number of days from the date of first dose to the date of earliest disease progression. All disease progression was included regardless of whether the event occurred while the participant was taking ABT-199 or had previously discontinued ABT-199. If the participant did not experience disease progression, then the data was censored at the date of last available disease assessment. Data for participants without any disease assessments performed after the baseline visit were censored at the date of first dose plus 1 day.

8. Time to First Response [Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up]

   Time to first response was defined as the number of days from the date of first dose to the date of the first sign of response (CR, CRi, nPR, or PR) given the participant has had a CR, CRi, confirmed nPR, or confirmed PR per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria. The first response could have been an assessment by physical exam as long as the results were later confirmed per the 2008 Modified IWCLL NCI-WG criteria. For participants who never experienced a response, the participant's data were not included in the analysis.

9. Time to 50% Reduction in Absolute Lymphocyte Count [Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up]

   Time to 50% reduction in absolute lymphocyte count (ALC) was defined as the number of days (hours if applicable) from the date of first dose to the date when the ALC had reduced to 50% of the baseline value. Only participants with a baseline of ALC > 5 × 10^9 /L were included in the analysis. For participants who never achieved a 50% reduction in ALC, the participant's data were not included in the analysis.

10. Overall Survival [Up to the data cutoff date of 15 December 2020, approximately 7.5 years of follow-up]

    Overall survival (OS) was defined as number of days from the date of first dose to the date of death. For participants who did not die, their data was censored at the date of last study visit or the last known date to be alive, whichever was later.

11. Percentage of Participants Who Moved on to Stem Cell Transplant [Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up]

    The percentage of participants who moved on to stem cell transplant was summarized.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center - North Campus /ID# 96748	Tucson	Arizona	United States	85719-1478
2	City of Hope /ID# 112875	Duarte	California	United States	91010
3	Moore UC San Diego Cancer Center /ID# 91793	La Jolla	California	United States	92093
4	Stanford University School of Med /ID# 105117	Stanford	California	United States	94305-2200
5	Georgetown University Hospital /ID# 96954	Washington	District of Columbia	United States	20007
6	Northwestern University Feinberg School of Medicine /ID# 92499	Chicago	Illinois	United States	60611-2927
7	The University of Chicago Medical Center /ID# 96960	Chicago	Illinois	United States	60637-1443
8	Ingalls Memorial Hosp /ID# 92497	Harvey	Illinois	United States	60426
9	Dana-Farber Cancer Institute /ID# 92494	Boston	Massachusetts	United States	02215
10	Henry Ford Health System /ID# 97795	Detroit	Michigan	United States	48202
11	Hackensack Univ Med Ctr /ID# 92500	Hackensack	New Jersey	United States	07601
12	Rutgers Cancer Institute of New Jersey /ID# 92513	New Brunswick	New Jersey	United States	08903
13	Columbia Univ Medical Center /ID# 103835	New York	New York	United States	10032-3725
14	Columbia Univ Medical Center /ID# 94716	New York	New York	United States	10032-3725
15	Cleveland Clinic Main Campus /ID# 92495	Cleveland	Ohio	United States	44195
16	University of Texas MD Anderson Cancer Center /ID# 92521	Houston	Texas	United States	77030
17	Royal North Shore Hospital /ID# 98836	St Leonards	New South Wales	Australia	2065
18	John Fawkner Private Hospital /ID# 98835	Coburg	Victoria	Australia	3058
19	Peter MacCallum Cancer Ctr /ID# 91795	Melbourne	Victoria	Australia	3000
20	Royal Melbourne Hospital /ID# 91794	Parkville	Victoria	Australia	3050
21	Duplicate_Jewish General Hospital /ID# 99476	Montreal	Quebec	Canada	H3T 1E2
22	Centre Hospitalier Lyon Sud /ID# 98839	Pierre Benite CEDEX	Auvergne-Rhone-Alpes	France	69495
23	Hopital Avicenne - APHP /ID# 98840	Bobigny	Ile-de-France	France	93000
24	Hopital Pitie Salpetriere /ID# 98842	Paris		France	75651
25	Centre Henri Becquerel /ID# 98838	Rouen		France	76038
26	Universitaetsklinik Heidelberg /ID# 98845	Heidelberg	Baden-Wuerttemberg	Germany	69120
27	Uniklinik Koeln /ID# 98847	Köln	Nordrhein-Westfalen	Germany	50937
28	Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 113235	Kiel	Schleswig-Holstein	Germany	24105
29	Universitaetsklinikum Ulm /ID# 92533	Ulm	Thueringen	Germany	89081
30	Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 113256	Dresden		Germany	01307
31	Universitaetsklinikum Freiburg /ID# 113276	Freiburg		Germany	79106
32	Universitaetsmedizin Goettingen /ID# 113258	Göttingen		Germany	37075
33	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz /ID# 113236	Mainz		Germany	55131
34	Muenchen Klinik Schwabing /ID# 113275	Muenchen		Germany	80804
35	Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie /ID# 98848	Lublin	Lubelskie	Poland	20-081
36	SP ZOZ Szpital Uniwersytecki w Krakowie /ID# 98849	Krakow	Malopolskie	Poland	31-501
37	Szpital Wojewodzki w Opolu /ID# 102855	Opole	Opolskie	Poland	46-020
38	Leicester Royal Infirmary /ID# 98865	Leicester	England	United Kingdom	LE1 5WW
39	The Royal Bournemouth Hospital /ID# 118975	Bournemouth		United Kingdom	BH7 7DW
40	Addenbrookes Hospital /ID# 119977	Cambridge		United Kingdom	CB2 0SP
41	St. James University Hospital /ID# 98863	Leeds		United Kingdom	LS9 7TF
42	Royal Liverpool and Broadgreen /ID# 98860	Liverpool		United Kingdom	L7 8XP
43	St Bartholomew's Hospital, Bar /ID# 98862	London		United Kingdom	EC1A 7BE
44	King's College Hospital NHS Foundation Trust /ID# 119975	London		United Kingdom	SE5 9RS
45	The Christie Hospital /ID# 98864	Manchester		United Kingdom	M20 4BX
46	Oxford Univ Hosp NHS Trust /ID# 119976	Oxford		United Kingdom	OX3 7LE
47	Derriford Hospital /ID# 118335	Plymouth		United Kingdom	PL6 8DH
48	Royal Marsden Hospital /ID# 98861	Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

• AbbVie
• Genentech, Inc.

Investigators

• Study Director: ABBVIE INC., AbbVie

Study Documents (Full-Text)

• Study Protocol - Feb 28, 2017
• Statistical Analysis Plan - Apr 27, 2018

More Information

Publications

• Stilgenbauer S, Eichhorst B, Schetelig J, Coutre S, Seymour JF, Munir T, Puvvada SD, Wendtner CM, Roberts AW, Jurczak W, Mulligan SP, Böttcher S, Mobasher M, Zhu M, Desai M, Chyla B, Verdugo M, Enschede SH, Cerri E, Humerickhouse R, Gordon G, Hallek M, Wierda WG. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016 Jun;17(6):768-778. doi: 10.1016/S1470-2045(16)30019-5. Epub 2016 May 10.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT01889186
• Other Study ID Numbers: M13-982; 2012-004027-20
• First Posted: Jun 28, 2013
• Last Update Posted: Dec 16, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by AbbVie: Chronic Lymphocytic Leukemia; 17p Deletion
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Venetoclax

Study Results

Participant Flow

Pre-assignment Detail	All treated participants: all participants who received at least one dose of ABT-199 in either the Main Cohort or Safety Expansion Cohort

Arm/Group Title	Main Cohort	Safety Expansion Cohort
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	107	51
COMPLETED	0	0
NOT COMPLETED	107	51

Baseline Characteristics

Arm/Group Title	Main Cohort	Safety Expansion Cohort	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	107	51	158
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.7 (9.87)	65.4 (9.97)	65.6 (9.87)
Sex: Female, Male (Count of Participants)
Female	37 34.6%	22 43.1%	59 37.3%
Male	70 65.4%	29 56.9%	99 62.7%
Race/Ethnicity, Customized (Count of Participants)
White	103 96.3%	49 96.1%	152 96.2%
Black	3 2.8%	1 2%	4 2.5%
Asian	0 0%	0 0%	0 0%
American Indian/Alaska Native	0 0%	0 0%	0 0%
Native Hawaiian or other Pacific Islander	0 0%	0 0%	0 0%
Other	0 0%	0 0%	0 0%
Multi race	0 0%	0 0%	0 0%
MISSING	1 0.9%	1 2%	2 1.3%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (Main Cohort)
Description	The overall response rate (ORR) is defined as the proportion of participants with an overall response (complete remission [CR] + complete remission with incomplete marrow recovery [CRi] + nodular partial remission [nPR] + partial remission [PR]) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria as assessed by the Independent Review Committee (IRC) in the first 70 participants treated in the Main Cohort.
Time Frame	Up to 36 weeks

Outcome Measure Data

Analysis Population Description

The first 70 participants who were treated with ABT-199 in the Main Cohort

Arm/Group Title	Main Cohort
Arm/Group Description	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.
Measure Participants	70
Number (95% Confidence Interval) [percentage of participants]	77.1 72.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Main Cohort
	Comments	The ORR for ABT-199 was tested to reject the null hypothesis of ORR = 40%. If the null hypothesis is rejected and the ORR is higher than 40%, then ABT-199 has been shown to have an ORR significantly higher than 40%.The p-value is from the exact binomial distribution comparing ABT-199 ORR to the 40% historical control rate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Clopper-Pearson exact method
	Comments

2. Primary Outcome

Title	Number of Participants With Adverse Events (Safety Expansion Cohort)
Description	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Time Frame	From the first dose of study drug until 30 days following last dose of study drug (up to 69 months)

Outcome Measure Data

Analysis Population Description

All treated participants in the Safety Expansion Cohort

Arm/Group Title	Safety Expansion Cohort
Arm/Group Description	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.
Measure Participants	51
Count of Participants [Participants]	51 47.7%

3. Secondary Outcome

Title	Overall Response Rate (ORR) (Safety Expansion Cohort)
Description	The overall response rate (ORR) is defined as the proportion of participants with an overall response (complete remission [CR] + complete remission with incomplete marrow recovery [CRi] + nodular partial remission [nPR] + partial remission [PR]) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria.
Time Frame	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Outcome Measure Data

Analysis Population Description

All treated participants in the Safety Expansion Cohort

Arm/Group Title	Safety Expansion Cohort
Arm/Group Description	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.
Measure Participants	51
Number (95% Confidence Interval) [percentage of participants]	82.4 77%

4. Secondary Outcome

Title	Complete Remission (CR) Rate
Description	Complete remission was defined as the proportion of participants who achieved a CR or Complete Remission with Incomplete Marrow Recovery(CRi ) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria. Participants who did not achieve a CR or CRi were considered to be non-responders in the calculation of CR rate.
Time Frame	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Outcome Measure Data

Analysis Population Description

All treated participants in the Main Cohort and the Safety Expansion Cohort

Arm/Group Title	Main Cohort	Safety Expansion Cohort
Arm/Group Description	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.	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.
Measure Participants	107	51
Number (95% Confidence Interval) [percentage of participants]	21.5 20.1%	27.5 53.9%

5. Secondary Outcome

Title	Partial Remission (PR) Rate
Description	PR rate was defined as the proportion of participants who achieved a nodular partial remission (nPR) or PR per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria. Participants who did not achieve a nPR or PR were considered to be non-responders in the calculation of PR rate.
Time Frame	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Outcome Measure Data

Analysis Population Description

All treated participants in the Main Cohort and the Safety Expansion Cohort

Arm/Group Title	Main Cohort	Safety Expansion Cohort
Arm/Group Description	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.	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.
Measure Participants	107	51
Number (95% Confidence Interval) [percentage of participants]	53.3 49.8%	54.9 107.6%

6. Secondary Outcome

Title	Duration of Overall Response
Description	Duration of overall response (DoR) was defined as the number of days from the date of first response (CR, CRi, nPR, or PR) by either CT scan or physical exam determination to the earliest recurrence (progressive disease; PD) or death. For participants who had a PR before CR, CRi, or nPR in subsequent visits, the DoR was computed from the earliest PR. If a participant was still responding, then their data was censored at the date of their last available disease assessment. To be included in the DoR analysis, participants must have had a response per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria (CR, CRi, confirmed nPR, or confirmed PR). For participants who never experienced response, their data was not included in the analysis.
Time Frame	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Outcome Measure Data

Analysis Population Description

All treated participants in the Main Cohort and the Safety Expansion Cohort with a response and available data

Arm/Group Title	Main Cohort	Safety Expansion Cohort
Arm/Group Description	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.	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.
Measure Participants	80	42
Median (95% Confidence Interval) [months]	35.3	NA

7. Secondary Outcome

Title	Progression-free Survival
Description	Duration of progression-free survival (PFS) was defined as the number of days from the date of first dose to the date of earliest disease progression or death. All disease progression was included regardless of whether the event occurred while the participant was taking ABT-199 or had previously discontinued ABT-199. If the participant does not experience disease progression or death, then the data was censored at the date of last disease assessment. Data for participants without any disease assessments performed after the baseline visit were censored at the date of first dose plus 1 day.
Time Frame	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Outcome Measure Data

Analysis Population Description

All treated participants in the Main Cohort and the Safety Expansion Cohort with available data

Arm/Group Title	Main Cohort	Safety Expansion Cohort
Arm/Group Description	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.	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.
Measure Participants	107	51
Median (95% Confidence Interval) [months]	24.7	30.2

8. Secondary Outcome

Title	Event-free Survival
Description	Event-free survival (EFS) was defined as the number of days from the date of first dose to the date of earliest disease progression, death, or start of a new anti-leukemic therapy. If the specified event (disease progression, death, start of a new anti-leukemic treatment) did not occur, participants were censored at the date of last disease assessment. Data for participants without any disease assessments performed after the baseline visit were censored at the date of first dose plus 1 day.
Time Frame	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Outcome Measure Data

Analysis Population Description

All treated participants in the Main Cohort and the Safety Expansion Cohort with available data

Arm/Group Title	Main Cohort	Safety Expansion Cohort
Arm/Group Description	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.	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.
Measure Participants	107	51
Median (95% Confidence Interval) [months]	24.7	30.2

9. Secondary Outcome

Title	Time to Progression
Description	Time to progression (TTP) was defined as the number of days from the date of first dose to the date of earliest disease progression. All disease progression was included regardless of whether the event occurred while the participant was taking ABT-199 or had previously discontinued ABT-199. If the participant did not experience disease progression, then the data was censored at the date of last available disease assessment. Data for participants without any disease assessments performed after the baseline visit were censored at the date of first dose plus 1 day.
Time Frame	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Outcome Measure Data

Analysis Population Description

All treated participants in the Main Cohort and the Safety Expansion Cohort with available data

Arm/Group Title	Main Cohort	Safety Expansion Cohort
Arm/Group Description	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.	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.
Measure Participants	107	51
Median (95% Confidence Interval) [months]	28.2	30.2

10. Secondary Outcome

Title	Time to First Response
Description	Time to first response was defined as the number of days from the date of first dose to the date of the first sign of response (CR, CRi, nPR, or PR) given the participant has had a CR, CRi, confirmed nPR, or confirmed PR per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria. The first response could have been an assessment by physical exam as long as the results were later confirmed per the 2008 Modified IWCLL NCI-WG criteria. For participants who never experienced a response, the participant's data were not included in the analysis.
Time Frame	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Outcome Measure Data

Analysis Population Description

All treated participants in the Main Cohort and the Safety Expansion Cohort with a response and available data

Arm/Group Title	Main Cohort	Safety Expansion Cohort
Arm/Group Description	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.	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.
Measure Participants	80	42
Mean (95% Confidence Interval) [months]	1.1	1.3

11. Secondary Outcome

Title	Time to 50% Reduction in Absolute Lymphocyte Count
Description	Time to 50% reduction in absolute lymphocyte count (ALC) was defined as the number of days (hours if applicable) from the date of first dose to the date when the ALC had reduced to 50% of the baseline value. Only participants with a baseline of ALC > 5 × 10^9 /L were included in the analysis. For participants who never achieved a 50% reduction in ALC, the participant's data were not included in the analysis.
Time Frame	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Outcome Measure Data

Analysis Population Description

All treated participants with a baseline of ALC > 5 × 10^9 /L, a 50% reduction in ALC, and available data

Arm/Group Title	Main Cohort	All Treated Participants
Arm/Group Description	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.	Participants in the Main Cohort received ABT-199 tablets once daily (QD) orally for up to 79 months,and those in the Safety Expansion Cohort received ABT-199 tablets once daily (QD) orally for up to 68 months. For both groups, the starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.
Measure Participants	85	125
Mean (95% Confidence Interval) [weeks]	1.1	1.2

12. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) was defined as number of days from the date of first dose to the date of death. For participants who did not die, their data was censored at the date of last study visit or the last known date to be alive, whichever was later.
Time Frame	Up to the data cutoff date of 15 December 2020, approximately 7.5 years of follow-up

Outcome Measure Data

Analysis Population Description

All treated participants with available data

Arm/Group Title	Main Cohort	Safety Expansion Cohort
Arm/Group Description	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.	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.
Measure Participants	107	51
Median (95% Confidence Interval) [months]	53.4	NA

13. Secondary Outcome

Title	Percentage of Participants Who Moved on to Stem Cell Transplant
Description	The percentage of participants who moved on to stem cell transplant was summarized.
Time Frame	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Outcome Measure Data

Analysis Population Description

All treated participants with available data

Arm/Group Title	Main Cohort	All Treated Participants
Arm/Group Description	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.	Participants in the Main Cohort received ABT-199 tablets once daily (QD) orally for up to 79 months,and those in the Safety Expansion Cohort received ABT-199 tablets once daily (QD) orally for up to 68 months. For both groups, the starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.
Measure Participants	107	158
Number (95% Confidence Interval) [percentage of participants]	2.8 2.6%	2.5 4.9%

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last study drug administration, up to 80 months for the Main Cohort and up to 69 months for the Safety Expansion Cohort.
Adverse Event Reporting Description	TEAEs and SAEs are defined as any AE or SAE with onset or worsening reported by a participant from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug. TEAEs were collected whether elicited or spontaneously reported by the participant.
Arm/Group Title	Main Cohort		Safety Expansion Cohort
Arm/Group Description	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.		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.
All Cause Mortality
	Main Cohort		Safety Expansion Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	62/107 (57.9%)		19/51 (37.3%)
Serious Adverse Events
	Main Cohort		Safety Expansion Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/107 (72.9%)		34/51 (66.7%)
Blood and lymphatic system disorders
ANAEMIA	4/107 (3.7%)	4	1/51 (2%)	1
AUTOIMMUNE HAEMOLYTIC ANAEMIA	7/107 (6.5%)	10	1/51 (2%)	1
FEBRILE NEUTROPENIA	7/107 (6.5%)	9	2/51 (3.9%)	2
HAEMOLYSIS	0/107 (0%)	0	1/51 (2%)	1
HAEMORRHAGIC DIATHESIS	1/107 (0.9%)	1	0/51 (0%)	0
IMMUNE THROMBOCYTOPENIA	1/107 (0.9%)	1	0/51 (0%)	0
LYMPHADENOPATHY	3/107 (2.8%)	3	1/51 (2%)	1
NEUTROPENIA	2/107 (1.9%)	2	2/51 (3.9%)	2
THROMBOCYTOPENIA	3/107 (2.8%)	3	1/51 (2%)	1
Cardiac disorders
ACUTE CORONARY SYNDROME	0/107 (0%)	0	1/51 (2%)	1
ACUTE MYOCARDIAL INFARCTION	1/107 (0.9%)	1	1/51 (2%)	1
ANGINA PECTORIS	2/107 (1.9%)	2	1/51 (2%)	1
ATRIAL FIBRILLATION	3/107 (2.8%)	3	0/51 (0%)	0
ATRIAL FLUTTER	1/107 (0.9%)	1	0/51 (0%)	0
ATRIOVENTRICULAR BLOCK SECOND DEGREE	0/107 (0%)	0	1/51 (2%)	1
CARDIAC ARREST	0/107 (0%)	0	1/51 (2%)	1
CARDIOGENIC SHOCK	1/107 (0.9%)	1	0/51 (0%)	0
CARDIOPULMONARY FAILURE	2/107 (1.9%)	2	0/51 (0%)	0
CORONARY ARTERY DISEASE	2/107 (1.9%)	3	0/51 (0%)	0
HYPERTENSIVE HEART DISEASE	1/107 (0.9%)	1	0/51 (0%)	0
MYOCARDIAL INFARCTION	1/107 (0.9%)	1	2/51 (3.9%)	2
MYOCARDIAL ISCHAEMIA	1/107 (0.9%)	1	0/51 (0%)	0
TACHYCARDIA	1/107 (0.9%)	1	0/51 (0%)	0
Congenital, familial and genetic disorders
ATRIAL SEPTAL DEFECT	1/107 (0.9%)	1	0/51 (0%)	0
HYDROCELE	1/107 (0.9%)	1	0/51 (0%)	0
Eye disorders
RETINAL ARTERY OCCLUSION	1/107 (0.9%)	1	0/51 (0%)	0
VISION BLURRED	0/107 (0%)	0	1/51 (2%)	1
Gastrointestinal disorders
ABDOMINAL PAIN	2/107 (1.9%)	2	1/51 (2%)	1
ABDOMINAL PAIN UPPER	2/107 (1.9%)	2	0/51 (0%)	0
APHTHOUS ULCER	1/107 (0.9%)	1	0/51 (0%)	0
ASCITES	1/107 (0.9%)	1	1/51 (2%)	1
DIARRHOEA	0/107 (0%)	0	2/51 (3.9%)	2
DYSPHAGIA	1/107 (0.9%)	1	0/51 (0%)	0
ENTERITIS	1/107 (0.9%)	1	0/51 (0%)	0
GASTRIC ULCER HAEMORRHAGE	1/107 (0.9%)	1	0/51 (0%)	0
INGUINAL HERNIA	1/107 (0.9%)	1	0/51 (0%)	0
INTESTINAL PSEUDO-OBSTRUCTION	0/107 (0%)	0	1/51 (2%)	1
NAUSEA	0/107 (0%)	0	1/51 (2%)	1
SMALL INTESTINAL OBSTRUCTION	0/107 (0%)	0	1/51 (2%)	1
TOOTH LOSS	1/107 (0.9%)	1	0/51 (0%)	0
UMBILICAL HERNIA	1/107 (0.9%)	1	0/51 (0%)	0
UPPER GASTROINTESTINAL HAEMORRHAGE	2/107 (1.9%)	2	0/51 (0%)	0
VOMITING	1/107 (0.9%)	1	1/51 (2%)	1
General disorders
GAIT DISTURBANCE	1/107 (0.9%)	1	0/51 (0%)	0
GENERAL PHYSICAL HEALTH DETERIORATION	4/107 (3.7%)	4	1/51 (2%)	1
HYPOTHERMIA	1/107 (0.9%)	1	0/51 (0%)	0
IMPAIRED HEALING	1/107 (0.9%)	1	0/51 (0%)	0
INFLUENZA LIKE ILLNESS	2/107 (1.9%)	2	0/51 (0%)	0
MULTIPLE ORGAN DYSFUNCTION SYNDROME	1/107 (0.9%)	1	0/51 (0%)	0
PAIN	1/107 (0.9%)	1	0/51 (0%)	0
PERFORMANCE STATUS DECREASED	1/107 (0.9%)	1	0/51 (0%)	0
PYREXIA	8/107 (7.5%)	8	0/51 (0%)	0
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME	1/107 (0.9%)	1	0/51 (0%)	0
Hepatobiliary disorders
CHOLANGITIS	1/107 (0.9%)	1	0/51 (0%)	0
CHOLELITHIASIS	1/107 (0.9%)	1	0/51 (0%)	0
HEPATIC FUNCTION ABNORMAL	1/107 (0.9%)	1	0/51 (0%)	0
Immune system disorders
HYPOGAMMAGLOBULINAEMIA	0/107 (0%)	0	1/51 (2%)	1
Infections and infestations
ADENOVIRUS INFECTION	1/107 (0.9%)	1	0/51 (0%)	0
APPENDICITIS	0/107 (0%)	0	1/51 (2%)	1
BETA HAEMOLYTIC STREPTOCOCCAL INFECTION	0/107 (0%)	0	1/51 (2%)	1
BRONCHITIS	2/107 (1.9%)	2	0/51 (0%)	0
BRONCHOPULMONARY ASPERGILLOSIS	1/107 (0.9%)	1	0/51 (0%)	0
CAMPYLOBACTER INFECTION	1/107 (0.9%)	2	0/51 (0%)	0
CELLULITIS	2/107 (1.9%)	2	0/51 (0%)	0
CLOSTRIDIUM DIFFICILE COLITIS	1/107 (0.9%)	2	0/51 (0%)	0
CLOSTRIDIUM DIFFICILE INFECTION	2/107 (1.9%)	3	0/51 (0%)	0
EMPYEMA	0/107 (0%)	0	1/51 (2%)	1
ERYSIPELAS	1/107 (0.9%)	2	0/51 (0%)	0
ESCHERICHIA INFECTION	0/107 (0%)	0	1/51 (2%)	1
ESCHERICHIA SEPSIS	0/107 (0%)	0	1/51 (2%)	1
ESCHERICHIA URINARY TRACT INFECTION	0/107 (0%)	0	1/51 (2%)	1
GASTROENTERITIS SALMONELLA	1/107 (0.9%)	1	0/51 (0%)	0
HERPES ZOSTER	3/107 (2.8%)	3	0/51 (0%)	0
HERPES ZOSTER CUTANEOUS DISSEMINATED	1/107 (0.9%)	1	0/51 (0%)	0
IMPETIGO	0/107 (0%)	0	1/51 (2%)	1
INFECTED SKIN ULCER	1/107 (0.9%)	2	0/51 (0%)	0
INFLUENZA	0/107 (0%)	0	1/51 (2%)	1
KLEBSIELLA BACTERAEMIA	1/107 (0.9%)	1	0/51 (0%)	0
KLEBSIELLA SEPSIS	0/107 (0%)	0	1/51 (2%)	1
LOWER RESPIRATORY TRACT INFECTION	2/107 (1.9%)	3	2/51 (3.9%)	3
METAPNEUMOVIRUS INFECTION	1/107 (0.9%)	1	0/51 (0%)	0
NASOPHARYNGITIS	1/107 (0.9%)	1	0/51 (0%)	0
NEUTROPENIC SEPSIS	1/107 (0.9%)	1	1/51 (2%)	2
OSTEOMYELITIS	0/107 (0%)	0	1/51 (2%)	1
PARAINFLUENZAE VIRUS INFECTION	0/107 (0%)	0	1/51 (2%)	1
PNEUMOCYSTIS JIROVECII INFECTION	1/107 (0.9%)	1	0/51 (0%)	0
PNEUMOCYSTIS JIROVECII PNEUMONIA	2/107 (1.9%)	2	0/51 (0%)	0
PNEUMONIA	14/107 (13.1%)	15	8/51 (15.7%)	9
PNEUMONIA FUNGAL	1/107 (0.9%)	1	0/51 (0%)	0
PNEUMONIA RESPIRATORY SYNCYTIAL VIRAL	1/107 (0.9%)	1	0/51 (0%)	0
POST PROCEDURAL INFECTION	1/107 (0.9%)	1	0/51 (0%)	0
PSEUDOMONAS INFECTION	0/107 (0%)	0	1/51 (2%)	1
PULMONARY MYCOSIS	1/107 (0.9%)	1	0/51 (0%)	0
PULMONARY SEPSIS	1/107 (0.9%)	1	0/51 (0%)	0
RESPIRATORY SYNCYTIAL VIRUS INFECTION	1/107 (0.9%)	1	0/51 (0%)	0
RHINOVIRUS INFECTION	1/107 (0.9%)	1	0/51 (0%)	0
SCROTAL ABSCESS	0/107 (0%)	0	1/51 (2%)	1
SCROTAL INFECTION	0/107 (0%)	0	1/51 (2%)	1
SEPSIS	2/107 (1.9%)	2	1/51 (2%)	1
SEPTIC SHOCK	1/107 (0.9%)	1	0/51 (0%)	0
SINUSITIS	0/107 (0%)	0	1/51 (2%)	1
SOFT TISSUE INFECTION	1/107 (0.9%)	1	0/51 (0%)	0
STAPHYLOCOCCAL INFECTION	1/107 (0.9%)	1	1/51 (2%)	1
UPPER RESPIRATORY TRACT INFECTION	2/107 (1.9%)	2	1/51 (2%)	1
URINARY TRACT INFECTION	3/107 (2.8%)	3	0/51 (0%)	0
UROSEPSIS	2/107 (1.9%)	2	0/51 (0%)	0
VASCULAR DEVICE INFECTION	0/107 (0%)	0	1/51 (2%)	1
VIRAL INFECTION	1/107 (0.9%)	1	0/51 (0%)	0
Injury, poisoning and procedural complications
ANASTOMOTIC LEAK	0/107 (0%)	0	1/51 (2%)	1
ANKLE FRACTURE	1/107 (0.9%)	1	0/51 (0%)	0
FEMORAL NECK FRACTURE	1/107 (0.9%)	2	0/51 (0%)	0
FEMUR FRACTURE	2/107 (1.9%)	2	0/51 (0%)	0
FOOT FRACTURE	1/107 (0.9%)	1	0/51 (0%)	0
JOINT DISLOCATION	1/107 (0.9%)	1	0/51 (0%)	0
MUSCLE STRAIN	0/107 (0%)	0	1/51 (2%)	1
RADIUS FRACTURE	1/107 (0.9%)	1	0/51 (0%)	0
Investigations
BLOOD CREATININE INCREASED	0/107 (0%)	0	1/51 (2%)	1
BLOOD GLUCOSE FLUCTUATION	0/107 (0%)	0	1/51 (2%)	1
CANDIDA TEST POSITIVE	1/107 (0.9%)	1	0/51 (0%)	0
ESCHERICHIA TEST POSITIVE	1/107 (0.9%)	1	0/51 (0%)	0
PLATELET COUNT DECREASED	1/107 (0.9%)	1	0/51 (0%)	0
Metabolism and nutrition disorders
CACHEXIA	1/107 (0.9%)	1	0/51 (0%)	0
DEHYDRATION	0/107 (0%)	0	1/51 (2%)	1
HYPERCALCAEMIA	1/107 (0.9%)	1	0/51 (0%)	0
HYPERKALAEMIA	0/107 (0%)	0	1/51 (2%)	1
HYPERPHOSPHATAEMIA	1/107 (0.9%)	2	0/51 (0%)	0
HYPONATRAEMIA	1/107 (0.9%)	1	0/51 (0%)	0
TUMOUR LYSIS SYNDROME	2/107 (1.9%)	2	3/51 (5.9%)	3
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/107 (0.9%)	1	0/51 (0%)	0
BACK PAIN	1/107 (0.9%)	1	0/51 (0%)	0
MUSCULOSKELETAL DISORDER	0/107 (0%)	0	1/51 (2%)	1
NECK PAIN	1/107 (0.9%)	1	1/51 (2%)	1
OSTEOARTHRITIS	1/107 (0.9%)	1	0/51 (0%)	0
OSTEONECROSIS	1/107 (0.9%)	1	0/51 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ACOUSTIC NEUROMA	1/107 (0.9%)	1	0/51 (0%)	0
ACUTE MYELOID LEUKAEMIA	2/107 (1.9%)	2	0/51 (0%)	0
ADENOCARCINOMA OF COLON	1/107 (0.9%)	1	0/51 (0%)	0
BASAL CELL CARCINOMA	1/107 (0.9%)	1	0/51 (0%)	0
BREAST CANCER	2/107 (1.9%)	2	0/51 (0%)	0
BRONCHIAL CARCINOMA	1/107 (0.9%)	1	0/51 (0%)	0
CENTRAL NERVOUS SYSTEM LYMPHOMA	1/107 (0.9%)	1	0/51 (0%)	0
CHRONIC LYMPHOCYTIC LEUKAEMIA	1/107 (0.9%)	1	0/51 (0%)	0
COLORECTAL CANCER	1/107 (0.9%)	1	1/51 (2%)	1
MALIGNANT MELANOMA	1/107 (0.9%)	1	0/51 (0%)	0
MALIGNANT NEOPLASM OF UNKNOWN PRIMARY SITE	1/107 (0.9%)	1	0/51 (0%)	0
MALIGNANT NEOPLASM PROGRESSION	18/107 (16.8%)	18	4/51 (7.8%)	4
MYELODYSPLASTIC SYNDROME	2/107 (1.9%)	2	0/51 (0%)	0
PLASMA CELL MYELOMA	0/107 (0%)	0	1/51 (2%)	1
SKIN PAPILLOMA	1/107 (0.9%)	1	0/51 (0%)	0
SQUAMOUS CELL CARCINOMA	2/107 (1.9%)	2	0/51 (0%)	0
SQUAMOUS CELL CARCINOMA OF SKIN	1/107 (0.9%)	1	0/51 (0%)	0
UTERINE CANCER	0/107 (0%)	0	1/51 (2%)	1
Nervous system disorders
ATAXIA	1/107 (0.9%)	1	0/51 (0%)	0
CEREBRAL INFARCTION	1/107 (0.9%)	1	0/51 (0%)	0
CHRONIC INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY	1/107 (0.9%)	1	0/51 (0%)	0
DISTURBANCE IN ATTENTION	1/107 (0.9%)	1	0/51 (0%)	0
HAEMORRHAGIC STROKE	1/107 (0.9%)	1	0/51 (0%)	0
PERIPHERAL SENSORY NEUROPATHY	1/107 (0.9%)	1	0/51 (0%)	0
PROGRESSIVE SUPRANUCLEAR PALSY	1/107 (0.9%)	1	0/51 (0%)	0
SYNCOPE	3/107 (2.8%)	3	0/51 (0%)	0
TRANSIENT ISCHAEMIC ATTACK	1/107 (0.9%)	1	0/51 (0%)	0
Psychiatric disorders
CONFUSIONAL STATE	1/107 (0.9%)	1	0/51 (0%)	0
DISORIENTATION	0/107 (0%)	0	1/51 (2%)	1
SUICIDAL IDEATION	0/107 (0%)	0	1/51 (2%)	1
Renal and urinary disorders
ACUTE KIDNEY INJURY	0/107 (0%)	0	1/51 (2%)	1
BLADDER DISORDER	1/107 (0.9%)	1	0/51 (0%)	0
CYSTITIS NONINFECTIVE	1/107 (0.9%)	1	0/51 (0%)	0
DYSURIA	1/107 (0.9%)	1	0/51 (0%)	0
HAEMATURIA	0/107 (0%)	0	1/51 (2%)	1
Reproductive system and breast disorders
VAGINAL PROLAPSE	0/107 (0%)	0	1/51 (2%)	1
Respiratory, thoracic and mediastinal disorders
BRONCHITIS CHRONIC	1/107 (0.9%)	1	0/51 (0%)	0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	1/107 (0.9%)	1	0/51 (0%)	0
DYSPNOEA	2/107 (1.9%)	2	0/51 (0%)	0
DYSPNOEA EXERTIONAL	1/107 (0.9%)	2	0/51 (0%)	0
EPISTAXIS	1/107 (0.9%)	3	0/51 (0%)	0
PLEURAL EFFUSION	0/107 (0%)	0	1/51 (2%)	1
PNEUMONIA ASPIRATION	1/107 (0.9%)	1	0/51 (0%)	0
PULMONARY EMBOLISM	1/107 (0.9%)	1	0/51 (0%)	0
PULMONARY MASS	1/107 (0.9%)	1	0/51 (0%)	0
Skin and subcutaneous tissue disorders
DECUBITUS ULCER	1/107 (0.9%)	2	0/51 (0%)	0
ERYTHEMA NODOSUM	1/107 (0.9%)	1	0/51 (0%)	0
SKIN HAEMORRHAGE	1/107 (0.9%)	1	0/51 (0%)	0
Vascular disorders
CIRCULATORY COLLAPSE	0/107 (0%)	0	1/51 (2%)	1
DEEP VEIN THROMBOSIS	2/107 (1.9%)	2	0/51 (0%)	0
HYPERTENSIVE CRISIS	1/107 (0.9%)	1	1/51 (2%)	1
HYPOTENSION	1/107 (0.9%)	1	0/51 (0%)	0
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	1/107 (0.9%)	1	0/51 (0%)	0
Other (Not Including Serious) Adverse Events
	Main Cohort		Safety Expansion Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	103/107 (96.3%)		50/51 (98%)
Blood and lymphatic system disorders
ANAEMIA	27/107 (25.2%)	55	11/51 (21.6%)	16
AUTOIMMUNE HAEMOLYTIC ANAEMIA	1/107 (0.9%)	1	3/51 (5.9%)	4
LEUKOPENIA	9/107 (8.4%)	14	2/51 (3.9%)	2
NEUTROPENIA	47/107 (43.9%)	127	22/51 (43.1%)	49
THROMBOCYTOPENIA	24/107 (22.4%)	55	9/51 (17.6%)	20
Ear and labyrinth disorders
VERTIGO	8/107 (7.5%)	9	2/51 (3.9%)	2
Gastrointestinal disorders
ABDOMINAL PAIN	8/107 (7.5%)	9	8/51 (15.7%)	9
ABDOMINAL PAIN UPPER	4/107 (3.7%)	5	4/51 (7.8%)	4
CONSTIPATION	11/107 (10.3%)	15	9/51 (17.6%)	10
DIARRHOEA	42/107 (39.3%)	60	26/51 (51%)	45
DYSPEPSIA	6/107 (5.6%)	6	3/51 (5.9%)	3
FLATULENCE	4/107 (3.7%)	4	3/51 (5.9%)	4
NAUSEA	35/107 (32.7%)	45	24/51 (47.1%)	32
VOMITING	17/107 (15.9%)	21	2/51 (3.9%)	2
General disorders
CHILLS	9/107 (8.4%)	9	5/51 (9.8%)	9
FATIGUE	27/107 (25.2%)	32	16/51 (31.4%)	18
OEDEMA PERIPHERAL	12/107 (11.2%)	15	5/51 (9.8%)	5
PAIN	9/107 (8.4%)	10	4/51 (7.8%)	5
PYREXIA	16/107 (15%)	22	6/51 (11.8%)	11
Infections and infestations
BRONCHITIS	13/107 (12.1%)	17	0/51 (0%)	0
CONJUNCTIVITIS	6/107 (5.6%)	7	3/51 (5.9%)	5
HERPES ZOSTER	6/107 (5.6%)	7	5/51 (9.8%)	5
INFLUENZA	6/107 (5.6%)	7	3/51 (5.9%)	3
LOWER RESPIRATORY TRACT INFECTION	4/107 (3.7%)	7	4/51 (7.8%)	6
NASOPHARYNGITIS	19/107 (17.8%)	32	8/51 (15.7%)	11
PNEUMONIA	7/107 (6.5%)	8	6/51 (11.8%)	6
RESPIRATORY TRACT INFECTION	11/107 (10.3%)	15	0/51 (0%)	0
SINUSITIS	6/107 (5.6%)	7	4/51 (7.8%)	6
SKIN INFECTION	0/107 (0%)	0	3/51 (5.9%)	4
TOOTH INFECTION	2/107 (1.9%)	2	3/51 (5.9%)	3
UPPER RESPIRATORY TRACT INFECTION	22/107 (20.6%)	36	15/51 (29.4%)	20
URINARY TRACT INFECTION	12/107 (11.2%)	15	8/51 (15.7%)	14
Injury, poisoning and procedural complications
ARTHROPOD BITE	1/107 (0.9%)	1	4/51 (7.8%)	4
FALL	7/107 (6.5%)	8	0/51 (0%)	0
Investigations
BLOOD CREATININE INCREASED	8/107 (7.5%)	11	2/51 (3.9%)	3
BLOOD LACTATE DEHYDROGENASE INCREASED	6/107 (5.6%)	6	3/51 (5.9%)	3
NEUTROPHIL COUNT DECREASED	3/107 (2.8%)	6	3/51 (5.9%)	3
PLATELET COUNT DECREASED	3/107 (2.8%)	3	3/51 (5.9%)	5
WEIGHT DECREASED	6/107 (5.6%)	10	0/51 (0%)	0
WEIGHT INCREASED	7/107 (6.5%)	9	1/51 (2%)	1
Metabolism and nutrition disorders
DECREASED APPETITE	6/107 (5.6%)	6	1/51 (2%)	1
HYPERKALAEMIA	6/107 (5.6%)	9	6/51 (11.8%)	9
HYPERPHOSPHATAEMIA	17/107 (15.9%)	20	3/51 (5.9%)	4
HYPOKALAEMIA	14/107 (13.1%)	25	5/51 (9.8%)	6
HYPOMAGNESAEMIA	3/107 (2.8%)	3	3/51 (5.9%)	5
HYPOPHOSPHATAEMIA	4/107 (3.7%)	7	4/51 (7.8%)	6
Musculoskeletal and connective tissue disorders
ARTHRALGIA	10/107 (9.3%)	11	9/51 (17.6%)	12
BACK PAIN	13/107 (12.1%)	16	7/51 (13.7%)	8
MUSCLE SPASMS	4/107 (3.7%)	4	5/51 (9.8%)	5
MYALGIA	2/107 (1.9%)	2	9/51 (17.6%)	10
PAIN IN EXTREMITY	6/107 (5.6%)	10	4/51 (7.8%)	5
Nervous system disorders
DIZZINESS	6/107 (5.6%)	7	7/51 (13.7%)	8
HEADACHE	16/107 (15%)	20	12/51 (23.5%)	12
Psychiatric disorders
INSOMNIA	4/107 (3.7%)	4	4/51 (7.8%)	4
Renal and urinary disorders
POLLAKIURIA	1/107 (0.9%)	1	3/51 (5.9%)	3
Respiratory, thoracic and mediastinal disorders
COUGH	16/107 (15%)	20	14/51 (27.5%)	19
DYSPNOEA	7/107 (6.5%)	7	7/51 (13.7%)	10
EPISTAXIS	6/107 (5.6%)	9	2/51 (3.9%)	2
NASAL CONGESTION	0/107 (0%)	0	3/51 (5.9%)	6
OROPHARYNGEAL PAIN	6/107 (5.6%)	7	3/51 (5.9%)	3
PRODUCTIVE COUGH	2/107 (1.9%)	2	3/51 (5.9%)	4
UPPER-AIRWAY COUGH SYNDROME	1/107 (0.9%)	1	3/51 (5.9%)	3
Skin and subcutaneous tissue disorders
ALOPECIA	4/107 (3.7%)	4	3/51 (5.9%)	4
DRY SKIN	7/107 (6.5%)	7	4/51 (7.8%)	5
NIGHT SWEATS	3/107 (2.8%)	3	3/51 (5.9%)	3
PRURITUS	7/107 (6.5%)	10	4/51 (7.8%)	4
RASH	11/107 (10.3%)	13	6/51 (11.8%)	6
SKIN LESION	2/107 (1.9%)	3	4/51 (7.8%)	4
Vascular disorders
HYPERTENSION	15/107 (14%)	19	4/51 (7.8%)	4

Limitations/Caveats

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Principal Investigators are NOT employed by the organization sponsoring the study.

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.