Clinical trial NCT01087151: 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)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: Rituxan
Apoptosis
BCl-2
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: AbbVie (prior sponsor, Abbott)
First posted: 2010-03-16
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Progression-free survival
timeFrame: From randomization to the first occurrence of progression, relapse, or death on study (approximately 40 months from First Patient In [FPI])
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Approximately 40 months from FPI
measure: Duration of response
timeFrame: Approximately 40 months from FPI
measure: Complete response (CR) rate
timeFrame: Approximately 40 months from FPI
measure: Progression-free survival as assessed by a blinded, independent review
timeFrame: From randomization to the first occurrence of progression, relapse, or death on study (approximately 40 months from FPI)
measure: ORR as assessed by a blinded, independent review
timeFrame: Approximately 40 months from FPI
measure: Duration of response as assessed by a blinded, independent review
timeFrame: Approximately 40 months from FPI
measure: CR rate as assessed by a blinded, independent review
timeFrame: Approximately 40 months from FPI
measure: Overall survival (OS)
timeFrame: From randomization until death due to any cause (approximately 4 years after Last Patient In)
Other outcomes:
Locations:
city: Alhambra
country: United States
state: California
city: Antioch
country: United States
state: California
city: Berkeley
country: United States
state: California
city: Burbank
country: United States
state: California
city: Duarte
country: United States
state: California
city: Dublin
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Northridge
country: United States
state: California
city: Pleasant Hill
country: United States
state: California
city: San Leandro
country: United States
state: California
city: San Luis Obispo
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: Fort Collins
country: United States
state: Colorado
city: Norwalk
country: United States
state: Connecticut
city: Bay Pines
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Decatur
country: United States
state: Illinois
city: Harvey
country: United States
state: Illinois
city: Tinley Park
country: United States
state: Illinois
city: Shreverport
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Bethesda
country: United States
state: Maryland
city: Bethesda
country: United States
state: Maryland
city: Randallstown
country: United States
state: Maryland
city: Lansing
country: United States
state: Michigan
city: Lansing
country: United States
state: Michigan
city: Omaha
country: United States
state: Nebraska
city: Henderson
country: United States
state: Nevada
city: Las Vegas
country: United States
state: Nevada
city: Las Vegas
country: United States
state: Nevada
city: Reno
country: United States
state: Nevada
city: Cherry Hill
country: United States
state: New Jersey
city: Farmington
country: United States
state: New Mexico
city: Oneida
country: United States
state: New York
city: Oswego
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Middletown
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Corpus Christi
country: United States
state: Texas
city: Lubbock
country: United States
state: Texas
city: Lubbock
country: United States
state: Texas
city: Everett
country: United States
state: Washington
city: Randwick
country: Australia
state: New South Wales
city: Greenslopes
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Kurralta Park
country: Australia
state: South Australia
city: Coburg, VIC
country: Australia
state: Victoria
city: Fitzroy
country: Australia
state: Victoria
city: Frankston
country: Australia
state: Victoria
city: Parkville
country: Australia
state: Victoria
city: Fremantle
country: Australia
state: Western Australia
city: Cachoeiro de Itapemirim
country: Brazil
state: ES
city: Belo Horizonte
country: Brazil
state: MG
city: Belo Horizonte
country: Brazil
state: MG
city: Rio de Janeiro
country: Brazil
state: RJ
city: Caxias do Sul
country: Brazil
state: RS
city: Porto Alegre
country: Brazil
state: RS
city: Porto Alegre
country: Brazil
state: RS
city: Porto Alegre
country: Brazil
state: RS
city: Santo Andre
country: Brazil
state: SP
city: São Paulo
country: Brazil
state: SP
city: Brno
country: Czech Republic
city: Hradec Kralove
country: Czech Republic
city: Prague 2
country: Czech Republic
city: Lille
country: France
city: Pierre Benite
country: France
city: Afula
country: Israel
city: Petah Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Rehovot
country: Israel
city: Modena
country: Italy
state: Emilia-Romagna
city: Genova
country: Italy
state: Liguria
city: Cremona
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Rozzano
country: Italy
state: Lombardia
city: Torino
country: Italy
state: Piemonte
city: Chorzow
country: Poland
city: Gdansk
country: Poland
city: Warszawa
country: Poland
city: San Juan
country: Puerto Rico
city: Kazan
country: Russian Federation
city: Moscow
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Cherkassy
country: Ukraine
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Khmelnitskyy
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Poltava
country: Ukraine
city: Zhytomir
country: Ukraine
city: Leicester
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Genentech, Inc.
name: William Ho, M.D., Ph.D.
role: STUDY_DIRECTOR
References: