A MULTICENTER, PHASE III, OPEN-LABEL, RANDOMIZED STUDY IN RELAPSED/REFRACTORY PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA TO EVALUATE THE BENEFIT OF GDC-0199 (ABT-199) PLUS RITUXIMAB COMPARED WITH BENDAMUSTINE PLUS RITUXIMAB

• Register: EUCTR
• Last refreshed on: 19 December 2016
• Main ID: EUCTR2013-002110-12-CZ
• Date of registration: 18/11/2013
• Prospective Registration: Yes
• Primary sponsor: AbbVie Deutschland GmbH & Co. KG
• Public title: A MULTICENTER, PHASE III, OPEN-LABEL, RANDOMIZED STUDY IN RELAPSED/REFRACTORY PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA TO EVALUATE THE BENEFIT OF GDC-0199 (ABT-199) PLUS RITUXIMAB COMPARED WITH BENDAMUSTINE PLUS RITUXIMAB
• Scientific title: A MULTICENTER, PHASE III, OPEN-LABEL, RANDOMIZED STUDY IN RELAPSED/REFRACTORY PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA TO EVALUATE THE BENEFIT OF GDC-0199 (ABT-199) PLUS RITUXIMAB COMPARED WITH BENDAMUSTINE PLUS RITUXIMAB
• Date of first enrolment: 26/02/2014
• Target sample size: 370
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002110-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Germany, Hungary, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Russian Federation, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd.

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
Diagnosis of CLL that meets published diagnostic criteria (Hallek et al. 2008).
Patients must have peripheral blood B-lymphocyte counts which clonally express CD5, CD19/20 and CD23 and are either kappa or lambda light-chain restricted.
Pro-lymphocytes may comprise no more than 55% of total circulating lymphocytes.
At initial diagnosis of CLL (ie, prior to front-line treatment), the peripheral lymphocyte count must have been >5000/mm3. Patients must meet the following criteria for relapsed or refractory CLL (per the iwCLL guidelines [Hallek et al. 2008]):
-Relapsed disease: a patient who previously achieved a CR or PR, but after a period of 6 months or more demonstrates evidence of progression;
-refractory disease: treatment failure or disease progression within 6 months of the last anti-leukemia therapy.
• Female patients who are not surgically sterile or postmenopausal (for at least 1 year) must practice at least one of the following methods of birth control throughout the duration of study participation and for at least 30 days 3 months after study treatment or 12 months after completing therapy with rituximab, whichever is later:
Total abstinence from sexual intercourse
A vasectomized partner
Hormonal contraceptives (oral, parenteral, vaginal ring, or transdermal) that started at least 3 months prior to study drug administration
Double-barrier method (condom ? diaphragm or cervical cup with spermicidal contraceptive sponge, jellies, or cream)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 185
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 185

Exclusion criteria:
Transformation of CLL to aggressive NHL (eg, Richter's transformation, prolymphocytic leukemia, or DLBCL) or CNS involvement by CLL.
Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology)
Patients with occult or prior hepatitis B infection (defined as positive total HBcAb and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly polymerase chain reaction (PCR) HBV DNA testing.
Positive test results for hepatitis C (HCV antibody serology testing)
Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
MedDRA version: 19.0 Level: LLT Classification code 10068852 Term: B-cell chronic lymphocytic leukaemia System Organ Class: 100000004864

Intervention(s)

Product Name: ABT-199 (GDC-0199)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ABT-199 (GDC-0199) 10 mg
Current Sponsor code: ABT-199
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: ABT-199 (GDC-0199)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ABT-199 (GDC-0199) 50 mg
Current Sponsor code: ABT-199
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: ABT-199 (GDC-0199)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ABT-199 (GDC-0199) 100 mg
Current Sponsor code: ABT-199
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: MabThera®
Product Name: Rituximab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Levact®
Product Name: Bendamustine
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: BENDAMUSTINE HYDROCHLORIDE
CAS Number: 3543-75-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2.5-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: September 2016 & September 2017

Secondary Objective: • To analyze Independent Review Committee (IRC) & investigator-assessed PFS in the subset of CLL patients with 17p deletion
• To evaluate PFS as assessed by an IRC.
• To evaluate rate of best OR (defined as CR, CRi, nodular partial response [nPR],
and PR), as assessed by the investigator
• To evaluate OR rate, CR, CRi, nPR and PR at end of combination treatment response visit, as assessed by the investigator
• To evaluate OR, CR, CRi, nPR and PR rates at end of combination treatment response visit, as assessed by the IRC.
• To evaluate overall survival (OS).
• To evaluate event-free survival (EFS)
• To evaluate duration of response for patients with a best overall response of CR, CRi, nPR, or PR.
• To evaluate time to next anti-CLL treatment.
• To evaluate the proportion of patients with MRD-negativity at the disease response assessment time points.

Primary end point(s): To evaluate the efficacy of GDC-0199 and rituximab (GDC-0199+R) compared with bendamustine and rituximab (BR) in patients with relapsed or refractory CLL as measured by investigator-assessed progression-free survival (PFS).

While the primary efficacy endpoint is investigator-assessed PFS, PFS based on IRC assessments will also be analyzed to support the primary analysis. In the United States, IRC-assessed PFS will be the basis for regulatory decisions.

Main Objective: To evaluate the efficacy of GDC-0199 and rituximab (GDC-0199+R) compared with bendamustine and rituximab (BR) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) as measured by investigator-assessed progression-free survival (PFS).

While the primary efficacy endpoint is investigator-assessed PFS, PFS based on IRC assessments will also be analyzed to support the primary analysis. In the United States, IRC-assessed PFS will be the basis for regulatory decisions.

Secondary Outcome(s)

Secondary end point(s): To analyze Independent Review Committee (IRC)-assessed PFS in the subset of CLL patients with 17p deletion identified by fluorescence in situ hybridization (FISH) testing performed at a central laboratory.

Timepoint(s) of evaluation of this end point: September 2017

Secondary ID(s)

GO28667

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

AbbVie Inc.