Please note that the ANZCTR website will be unavailable from 9am until 9.30am (AEST) on Monday 22nd July for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00481091




Registration number
NCT00481091
Ethics application status
Date submitted
30/05/2007
Date registered
1/06/2007
Date last updated
11/04/2019

Titles & IDs
Public title
A Phase 1/2a Study of ABT-263 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia
Scientific title
A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABT-263 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia
Secondary ID [1] 0 0
2007-002143-25
Secondary ID [2] 0 0
M06-873
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 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
Description of intervention(s) / exposure
Treatment: Drugs - ABT-263

Experimental: Arm NA, Group is Applicable - Group/Cohort Number or Label is numerical and sequential starting with dose level 1


Treatment: Drugs: ABT-263
Phase 1 dosing under two different schedules: 14 days on drug, 7 days or (14/21) or continuous dosing.
Phase 2a dosing at the recommended phase 2a dose and schedule

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

Outcomes
Primary outcome [1] 0 0
Number of Subjects with Adverse Events in the in the Dose Escalation Phase (Phase 1) - Treatment emergent adverse events defined as any adverse event from the time of study drug administration until 30 days after the last dose of study drug.
Timepoint [1] 0 0
From first dose of study drug to 30 days after the last dose of study drug (up to approximately 13 years)
Primary outcome [2] 0 0
Number of participants with Potentially Clinically Significant (PCS) Hematology Values in the Dose Escalation Phase (Phase 1) - Blood samples for clinical laboratory tests will be collected throughout the study for clinical laboratory tests.
Timepoint [2] 0 0
Up to approximately 13 years
Primary outcome [3] 0 0
Number of participants with PCS Clinical Chemistry Values in the Dose Escalation Phase (Phase 1) - Blood samples for clinical laboratory tests will be collected throughout the study for clinical laboratory tests.
Timepoint [3] 0 0
Up to approximately 13 years
Primary outcome [4] 0 0
Number of participants with PCS Vital Signs Values in the Dose Escalation Phase (Phase 1) - Vital signs will be collected throughout the study for clinical laboratory tests.
Timepoint [4] 0 0
Up to approximately 13 years
Primary outcome [5] 0 0
Number of Participants with Dose Limiting Toxicity (DLT) in the Dose Escalation Phase (Phase 1) - DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0.
Timepoint [5] 0 0
Cycle 1 (14 days on therapy and 7 days off therapy OR 21 days continuous dosing)
Primary outcome [6] 0 0
Maximum Tolerated Dose (MTD) in the Dose Escalation Phase (Phase 1) - The MTD will be determined by using available clinical data during dose escalation in phase 1.
Timepoint [6] 0 0
Cycle 1 (14 days on therapy and 7 days off therapy OR 21 days continuous dosing)
Primary outcome [7] 0 0
Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase (Phase 1) - The RPTD will be determined based on observed dose-limiting toxicities (DLTs) and/or determination of the maximum tolerated dose (MTD) in phase 1.
Timepoint [7] 0 0
Cycle 1 (14 days on therapy and 7 days off therapy OR 21 days continuous dosing)
Primary outcome [8] 0 0
Plasma Concentrations of navitoclax on Cycle 1, Day 1 in the Dose Escalation Phase (Phase 1) - Plasma concentrations of navitoclax
Timepoint [8] 0 0
Day 1
Primary outcome [9] 0 0
Plasma Concentrations of navitoclax on Cycle 1, Day 14 in the Dose Escalation Phase (Phase 1) - Plasma concentrations of navitoclax
Timepoint [9] 0 0
Day 14
Primary outcome [10] 0 0
Maximum Serum Concentration (Cmax) of navitoclax on Cycle 1, Day 1 in the Dose Escalation Phase (Phase 1) - Cmax of navitoclax.
Timepoint [10] 0 0
Day 1
Primary outcome [11] 0 0
Cmax of navitoclax on Cycle 1, Day 14 in the Dose Escalation Phase (Phase 1) - Cmax of navitoclax.
Timepoint [11] 0 0
Day 14
Primary outcome [12] 0 0
Area Under the Plasma Concentration-time Curve over time from 0 to 24 hours (AUC0-24) of navitoclax on Cycle 1, Day 1 in the Dose Escalation Phase (Phase 1) - AUC0-24 of navitoclax.
Timepoint [12] 0 0
Day 1
Primary outcome [13] 0 0
AUC0-24 of navitoclax on Cycle 1, Day 14 in the Dose Escalation Phase (Phase 1) - AUC0-24 of navitoclax.
Timepoint [13] 0 0
Day 14
Primary outcome [14] 0 0
Time to Maximum Observed Plasma Concentration (Tmax) of navitoclax on Cycle 1, Day 1 in the Dose Escalation Phase (Phase 1) - Cmax of navitoclax.
Timepoint [14] 0 0
Day 1
Primary outcome [15] 0 0
Tmax of navitoclax on Cycle 1, Day 14 in the Dose Escalation Phase (Phase 1) - Cmax of navitoclax.
Timepoint [15] 0 0
Day 14
Primary outcome [16] 0 0
Number of Subjects with Adverse Events in the Recommended Phase 2 Dose Phase (Phase 2) - Treatment emergent adverse events defined as any adverse event from the time of study drug administration until 30 days after the last dose of study drug.
Timepoint [16] 0 0
From first dose of study drug to 30 days after the last dose of study drug (up to approximately 13 years)
Primary outcome [17] 0 0
Number of participants with PCS Hematology Values in the Recommended Phase 2 (RPTD) Phase (Phase 2) - Blood samples for clinical laboratory tests will be collected throughout the study for clinical laboratory tests.
Timepoint [17] 0 0
Up to approximately 13 years
Primary outcome [18] 0 0
Number of participants with PCS Clinical Chemistry Values in the Recommended Phase 2 Dose (RPTD) Phase (Phase 2) - Blood samples for clinical laboratory tests will be collected throughout the study for clinical laboratory tests.
Timepoint [18] 0 0
Up to approximately 13 years
Primary outcome [19] 0 0
Number of participants with PCS Vital Signs Values in the Recommended Phase 2 Dose (RPTD) Phase (Phase 2) - Vital signs will be collected throughout the study for clinical laboratory tests.
Timepoint [19] 0 0
Up to approximately 13 years
Primary outcome [20] 0 0
Plasma Concentrations of navitoclax on Cycle 1, Day 15 in the Recommended Phase 2 Dose (RPTD) Phase (Phase 2) - Plasma concentrations of navitoclax
Timepoint [20] 0 0
Day 15
Primary outcome [21] 0 0
Cmax of navitoclax on Cycle 1, Day 15 in the Recommended Phase 2 Dose (RPTD) Phase (Phase 2) - Cmax of navitoclax.
Timepoint [21] 0 0
Day 15
Primary outcome [22] 0 0
AUC0-24 of navitoclax on Cycle 1, Day 15 in the Recommended Phase 2 Dose (RPTD) Phase (Phase 2) - AUC0-24 of navitoclax.
Timepoint [22] 0 0
Day 15
Primary outcome [23] 0 0
Tmax of navitoclax on Cycle 1, Day 15 in the Recommended Phase 2 Dose (RPTD) Phase (Phase 2) - Cmax of navitoclax.
Timepoint [23] 0 0
Day 15
Primary outcome [24] 0 0
Number of Subjects with Adverse Events in the Extension Study - Treatment emergent adverse events defined as any adverse event from the time of study drug administration until 30 days after the last dose of study drug.
Timepoint [24] 0 0
From first dose of study drug to 30 days after the last dose of study drug (up to approximately 13 years)
Primary outcome [25] 0 0
Number of participants with PCS Hematology Values in the Extension Study - Blood samples for clinical laboratory tests will be collected throughout the study for clinical laboratory tests.
Timepoint [25] 0 0
Up to approximately 13 years
Primary outcome [26] 0 0
Number of participants with PCS Clinical Chemistry Values in the Extension Study - Blood samples for clinical laboratory tests will be collected throughout the study for clinical laboratory tests.
Timepoint [26] 0 0
Up to approximately 13 years
Primary outcome [27] 0 0
Number of participants with PCS Vital Signs Values in the Extension Study - Vital signs will be collected throughout the study for clinical laboratory tests.
Timepoint [27] 0 0
Up to approximately 13 years
Primary outcome [28] 0 0
Progression-free Survival (PFS) - PFS defined as the time from the date the participant started study drug to the date the participant experiences an event of disease progression.
Timepoint [28] 0 0
Up to approximately 13 years
Primary outcome [29] 0 0
Overall Survival (OS) - OS defined as the time from the date the participant started study drug to the date the participant's death.
Timepoint [29] 0 0
Up to approximately 13 years

Eligibility
Key inclusion criteria
- Relapsed or refractory Chronic Lymphocytic Leukemia and require treatment in opinion
of investigator

- Eastern Cooperative Oncology Group (ECOG) <= 1

- Adequate bone marrow independent of growth factor support, renal and hepatic function
per defined laboratory criteria
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History or clinically suspicious for cancer-related Central Nervous System disease

- Receipt of allogenic or autologous stem cell transplant

- Recent history (within 1 year of first dose) of underlying, predisposing condition of
bleeding or currently exhibits signs of bleeding

- Active peptic ulcer disease or other potentially hemorrhagic esophagitis/gastritis

- Active immune thrombocytopenic purpura or history of being refractory to platelet
transfusions (within 1 year of first dose)

Study design
Purpose of the study
Treatment
Allocation to intervention
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 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Ctr /ID# 6583 - Melbourne
Recruitment hospital [2] 0 0
Royal Melbourne Hospital /ID# 5576 - Parkville
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Nebraska
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
Germany
State/province [7] 0 0
Nordrhein-Westfalen
Country [8] 0 0
United Kingdom
State/province [8] 0 0
England

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
The Phase 1 portion of the study will evaluate the pharmacokinetic profile and safety of
ABT-263 under two different dosing schedules with the objective of defining the dose limiting
toxicity and maximum tolerated dose. The Phase 2a portion of the study will evaluate ABT-263
at the defined recommended Phase 2 dose to obtain additional safety information and a
preliminary assessment of efficacy. The Extension Study portion will allow active subjects to
continue to receive ABT-263 for up to 9 years after the last subject transitions with less
frequent study evaluations.
Trial website
https://clinicaltrials.gov/show/NCT00481091
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

Summary results
Other publications