A Study of ABT-263 in Combination With Dose-Intensive Rituximab, or Dose-Intensive Rituximab Alone, in Previously Untreated Patients With B-Cell, Chronic Lymphocytic Leukemia (CLL)

Sponsor

Genentech, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01087151

Collaborator

AbbVie (prior sponsor, Abbott) (Industry)

118

Enrollment

103

Locations

Arms

Duration (Months)

1.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase II, randomized, open-label, international, multicenter trial is designed to evaluate the safety and efficacy of rituximab monotherapy when given according to a dose intense regimen and to assess the safety, efficacy, and pharmacokinetics of ABT-263 when combined with dose-intense rituximab in previously untreated patients with B-cell CLL.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Drug: ABT-263 Drug: rituximab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

118 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II, Multicenter, Randomized, Controlled, Open-label Study of the Safety, Efficacy and Pharmacokinetics of ABT-263 in Combination With Dose-intensive Rituximab, or Dose-intensive Rituximab Alone, in Previously Untreated Patients With B-Cell, Chronic Lymphocytic Leukemia (CLL)

Study Start Date :

Aug 1, 2010

Actual Primary Completion Date :

Jun 1, 2012

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A	Drug: rituximab Intravenous repeating dose
Experimental: B	Drug: ABT-263 Oral repeating dose Drug: rituximab Intravenous repeating dose
Experimental: C	Drug: ABT-263 Oral repeating dose Drug: rituximab Intravenous repeating dose

Arm

Intervention/Treatment

Active Comparator: A

Drug: rituximab

Intravenous repeating dose

Experimental: B

Drug: ABT-263

Oral repeating dose

Drug: rituximab

Intravenous repeating dose

Experimental: C

Drug: ABT-263

Oral repeating dose

Drug: rituximab

Intravenous repeating dose

Outcome Measures

Primary Outcome Measures

Progression-free survival [From randomization to the first occurrence of progression, relapse, or death on study (approximately 40 months from First Patient In [FPI])]

Secondary Outcome Measures

Overall response rate (ORR) [Approximately 40 months from FPI]
Duration of response [Approximately 40 months from FPI]
Complete response (CR) rate [Approximately 40 months from FPI]
Progression-free survival as assessed by a blinded, independent review [From randomization to the first occurrence of progression, relapse, or death on study (approximately 40 months from FPI)]
ORR as assessed by a blinded, independent review [Approximately 40 months from FPI]
Duration of response as assessed by a blinded, independent review [Approximately 40 months from FPI]
CR rate as assessed by a blinded, independent review [Approximately 40 months from FPI]
Overall survival (OS) [From randomization until death due to any cause (approximately 4 years after Last Patient In)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Previously untreated, CD20-positive B-cell CLL
ECOG performance status of 0 or 1
Life expectancy > 6 months
Willingness and capability to be accessible for follow-up until study termination or death
For patients of reproductive potential (both males and females), use of a reliable means of contraception

Exclusion Criteria:

Prolymphocytic leukemia
Richter's transformation to an aggressive B-cell malignancy (e.g., DLBCL)
Prior radiotherapy to a lesion(s) that will be used to assess response unless that lesion(s) shows clear evidence of progression at baseline
Patients with a history of other malignancies within 2 years prior to study entry except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin carcinoma, low-grade, localized prostate cancer treated surgically with curative intent or one that carries a good prognosis, in situ ductal carcinoma of the breast treated with lumpectomy alone with curative intent
Prior treatment with rituximab, ABT-263 or other pro-apoptotic agents
Current or recent (within the 28 days prior to initiation of study treatment) participation in another experimental drug study
Major surgical procedure (excluding lymph node biopsy) or significant traumatic injury within 28 days prior to treatment onset or anticipation of the need for major surgery during the course of the study
Active infection requiring parenteral antibiotics or antiviral or antifungal agents at the onset of study treatment
Receipt of primary or booster vaccination with live-virus vaccines for up to 6 months prior to initiation of study treatment
Patients receiving therapeutic anticoagulation with heparin or warfarin or patients receiving any drugs or herbal supplements that are known to inhibit platelet function (including low-dose aspirin) within 7 days of the first dose of ABT-263. Note: Patients receiving low-dose anticoagulation for the purpose of maintaining central venous catheter patency are eligible.
Patients who have an inherited or acquired bleeding diathesis, including (but not limited to) hemophilia or immune or thrombotic thrombocytopenic purpura, or who have had an underlying condition that predisposes to abnormal bleeding (e.g., peptic ulcer disease) within 1 year prior to the first dose of ABT-263
Patients with a history of refractoriness to platelet transfusions
Clinically significant cardiovascular disease
Known human immunodeficiency virus (HIV) infection, seropositivity for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody or RNA
Pregnancy or breastfeeding
Concurrent (or within 7 days prior to the first dose of study treatment) systemic corticosteroid therapy except some low-dose corticosteroid therapies
History of other disease, metabolic dysfunction, physical or laboratory finding(s) giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, might affect interpretation of the results of the study or render the patient at high risk from treatment complications
History of anaphylaxis, allergic reaction, or hypersensitivity to sulfites (sodium metabisulphite is included in study drug formulation)
Any contraindication to alcohol ingestion (study drug formulation includes approximately 15% ethanol)

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Alhambra	California	United States	91801
2	Antioch	California	United States	94531
3	Berkeley	California	United States	94704
4	Burbank	California	United States	91505
5	Duarte	California	United States	91010
6	Dublin	California	United States	94568
7	La Jolla	California	United States	92093
8	Los Angeles	California	United States	90024
9	Los Angeles	California	United States	90073
10	Los Angeles	California	United States	90095-1772
11	Los Angeles	California	United States	90095
12	Northridge	California	United States	91325
13	Pleasant Hill	California	United States	94523
14	San Leandro	California	United States	94578-2626
15	San Luis Obispo	California	United States	93454
16	Santa Monica	California	United States	90404
17	Fort Collins	Colorado	United States	80528
18	Norwalk	Connecticut	United States	06856
19	Bay Pines	Florida	United States	33744
20	Atlanta	Georgia	United States	30322
21	Chicago	Illinois	United States	60612
22	Decatur	Illinois	United States	62526
23	Harvey	Illinois	United States	60426
24	Tinley Park	Illinois	United States	60477
25	Shreverport	Louisiana	United States	71103
26	Baltimore	Maryland	United States	21215
27	Bethesda	Maryland	United States	20817
28	Bethesda	Maryland	United States	20874
29	Randallstown	Maryland	United States	21133
30	Lansing	Michigan	United States	48909
31	Lansing	Michigan	United States	48912
32	Omaha	Nebraska	United States	68114
33	Henderson	Nevada	United States	89052
34	Las Vegas	Nevada	United States	89148
35	Las Vegas	Nevada	United States	89169
36	Reno	Nevada	United States	89502
37	Cherry Hill	New Jersey	United States	08003
38	Farmington	New Mexico	United States	87401
39	Oneida	New York	United States	13421
40	Oswego	New York	United States	13126
41	Syracuse	New York	United States	13210
42	Middletown	Ohio	United States	45042
43	Philadelphia	Pennsylvania	United States	19111
44	Pittsburgh	Pennsylvania	United States	15224
45	Corpus Christi	Texas	United States	78405
46	Lubbock	Texas	United States	79410
47	Lubbock	Texas	United States	79415
48	Everett	Washington	United States	98201
49	Randwick	New South Wales	Australia	2031
50	Greenslopes	Queensland	Australia	4120
51	Adelaide	South Australia	Australia	5000
52	Kurralta Park	South Australia	Australia	5037
53	Coburg, VIC	Victoria	Australia	3058
54	Fitzroy	Victoria	Australia	3065
55	Frankston	Victoria	Australia	3199
56	Parkville	Victoria	Australia	3052
57	Fremantle	Western Australia	Australia	6160
58	Cachoeiro de Itapemirim	ES	Brazil	29308-014
59	Belo Horizonte	MG	Brazil	30150-270
60	Belo Horizonte	MG	Brazil	30150-281
61	Rio de Janeiro	RJ	Brazil	20211-030
62	Caxias do Sul	RS	Brazil	95070-560
63	Porto Alegre	RS	Brazil	90020-090
64	Porto Alegre	RS	Brazil	90035-003
65	Porto Alegre	RS	Brazil	90110-270
66	Santo Andre	SP	Brazil	09060-650
67	São Paulo	SP	Brazil	01427-001
68	Brno		Czech Republic	625 00
69	Hradec Kralove		Czech Republic	500 05
70	Prague 2		Czech Republic	128 08
71	Lille		France	59037
72	Pierre Benite		France	69495
73	Afula		Israel	18101
74	Petah Tikva		Israel	4937211
75	Ramat Gan		Israel	5262100
76	Rehovot		Israel	76100
77	Modena	Emilia-Romagna	Italy	41100
78	Genova	Liguria	Italy	16128
79	Cremona	Lombardia	Italy	26100
80	Milano	Lombardia	Italy	20133
81	Milano	Lombardia	Italy	20162
82	Rozzano	Lombardia	Italy	20089
83	Torino	Piemonte	Italy	10128
84	Chorzow		Poland	41-500
85	Gdansk		Poland	80-952
86	Warszawa		Poland	00-909
87	San Juan		Puerto Rico	00927
88	Kazan		Russian Federation	420029
89	Moscow		Russian Federation	115478
90	Petrozavodsk		Russian Federation	185019
91	Ryazan		Russian Federation	390039
92	St. Petersburg		Russian Federation	191024
93	Cherkassy		Ukraine	18009
94	Dnipropetrovsk		Ukraine	49102
95	Donetsk		Ukraine	83045
96	Ivano-Frankivsk		Ukraine	76018
97	Khmelnitskyy		Ukraine	29000
98	Kyiv		Ukraine	03150
99	Lviv		Ukraine	79044
100	Poltava		Ukraine	36024
101	Zhytomir		Ukraine	10002
102	Leicester		United Kingdom	LE1 5WW
103	London		United Kingdom	EC1A 7BE