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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT00481091
Ethics application status
Date submitted
30/05/2007
Date registered
1/06/2007
Date last updated
13/06/2023

Titles & IDs
Public title
A Study of ABT-263 in Participants 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: Navitoclax 14/21 Day Cycle: 10 mg - Navitoclax 10 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.

Experimental: Navitoclax 14/21 Day Cycle: 110 mg - Navitoclax 110 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.

Experimental: Navitoclax 14/21 Day Cycle: 200 mg - Navitoclax 200 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.

Experimental: Navitoclax 14/21 Day Cycle: 250 mg - Navitoclax 250 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle.

Experimental: Navitoclax 21/21 Day Cycle: 125 mg - Navitoclax 125 mg administered for 21 consecutive days to complete a 21-day cycle.

Experimental: Navitoclax 21/21 Day Cycle: 200 mg - Navitoclax 200 mg administered for 21 consecutive days to complete a 21-day cycle.

Experimental: Navitoclax 21/21 Day Cycle: 250 mg - Navitoclax 250 mg administered for 21 consecutive days to complete a 21-day cycle.

Experimental: Navitoclax 21/21 Day Cycle: 300 mg - Navitoclax 300 mg administered for 21 consecutive days to complete a 21-day cycle.

Experimental: Phase 2: Navitoclax 100 mg - Navitoclax 100 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s).

Experimental: Phase 2: Navitoclax 250 mg - Navitoclax 250 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s).


Treatment: Drugs: ABT-263
Tablet; Oral
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to Adverse Events (AEs)
Timepoint [1] 0 0
From first dose of study drug to 30 days post-last dose. Participants enrolled in the 14/21-day cycle received a mean of 21.7 treatment cycles; participants enrolled in the 21/21-day cycle received a mean of 19.4 treatment cycles.
Primary outcome [2] 0 0
Phase 1: Number of Participants With DLTs in the Dose Escalation Phase
Timepoint [2] 0 0
Cycle 1 (Up to 21 days) plus 7 days
Primary outcome [3] 0 0
Phase 1: Maximum Tolerated Dose (MTD) in the Dose Escalation Phase
Timepoint [3] 0 0
Cycle 1 (Up to 21 days) plus 7 days
Primary outcome [4] 0 0
Phase 1: Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase
Timepoint [4] 0 0
Cycle 1 (Up to 21 days) plus 7 days
Primary outcome [5] 0 0
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax
Timepoint [5] 0 0
Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Primary outcome [6] 0 0
Phase 1: Maximum Observed Plasma Concentration (Cmax)
Timepoint [6] 0 0
Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Primary outcome [7] 0 0
Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 8 (AUC8)
Timepoint [7] 0 0
Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Primary outcome [8] 0 0
Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 24 (AUC24)
Timepoint [8] 0 0
Cycle 1 Day 1: pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Cycle 1 Days 14: pre-dose, 2, 4, 6, 8
Primary outcome [9] 0 0
Phase 1: Cmax/Dose
Timepoint [9] 0 0
Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Primary outcome [10] 0 0
Phase 1: AUC8/Dose
Timepoint [10] 0 0
Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Primary outcome [11] 0 0
Phase 1: AUC24/Dose
Timepoint [11] 0 0
Cycle 1 Day 1: pre-dose, 2, 4, 6, 8, and 24 hours post-dose; Cycle 1 Days 14: pre-dose, 2, 4, 6, 8
Primary outcome [12] 0 0
Phase 1: Terminal Phase Elimination Rate Constant (ß) for Navitoclax
Timepoint [12] 0 0
Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
Primary outcome [13] 0 0
Phase 1: Terminal Phase Elimination Half-life (t1/2) of Navitoclax
Timepoint [13] 0 0
Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
Primary outcome [14] 0 0
Phase 2: Number of Participants With TEAEs, SAEs, and Discontinuations Due to AEs
Timepoint [14] 0 0
From first dose of study drug to 30 days post-last dose. Participants enrolled in Phase 2 received a mean of 15.6 treatment cycles.
Primary outcome [15] 0 0
Phase 2: Dose-Normalized Plasma Concentrations After Navitoclax Once Daily Dosing
Timepoint [15] 0 0
Cycle 1 Day 1: 4-8 h postdose; Cycle 1 Day 15: predose; Cycle 3 Day 1: predose, 4-8 h postdose; Cycle 5 Day 1: predose, 4-8 h postdose; Cycle 7 Day 1: predose, 4-8 h postdose; Cycle 9 Day 1: predose, 4-8 h postdose

Eligibility
Key inclusion criteria
* Relapsed or refractory CLL 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
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History or is 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
Non-randomised trial
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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/07/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/05/2022
Sample size
Target
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Ctr /ID# 6583 - Melbourne
Recruitment hospital [2] 0 0
The 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 11 years after the last subject transitions with less frequent study evaluations.
Trial website
https://clinicaltrials.gov/study/NCT00481091
Trial related presentations / publications
Roberts AW, Seymour JF, Brown JR, Wierda WG, Kipps TJ, Khaw SL, Carney DA, He SZ, Huang DC, Xiong H, Cui Y, Busman TA, McKeegan EM, Krivoshik AP, Enschede SH, Humerickhouse R. Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol. 2012 Feb 10;30(5):488-96. doi: 10.1200/JCO.2011.34.7898. Epub 2011 Dec 19.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00481091