CompletedNCT00481091Updated Jun 13, 2023Results posted

A Study of ABT-263 in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia

A Phase 1/2 interventional study of ABT-263 in Chronic Lymphocytic Leukemia, sponsored by AbbVie. Completed at 10 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-06-13.

Sponsored by AbbVie · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 60
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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.

Conditions studied

Chronic Lymphocytic Leukemia

Browse trials for

Keywords

Chronic Lymphocytic Leukemia (CLL)
Navitoclax
ABT-263
Cancer

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 60 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

AbbVie is the lead sponsor of 953 studies on the registry; 136 are open to participants now.

Of its 350 completed or terminated interventional studies of FDA-regulated products, 210 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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.

Exclusion criteria

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

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 60 participants (actual)

Study arms

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.
Drug: ABT-263
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.
Drug: ABT-263
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.
Drug: ABT-263
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.
Drug: ABT-263
Experimental
Navitoclax 21/21 Day Cycle: 125 mg
Navitoclax 125 mg administered for 21 consecutive days to complete a 21-day cycle.
Drug: ABT-263
Experimental
Navitoclax 21/21 Day Cycle: 200 mg
Navitoclax 200 mg administered for 21 consecutive days to complete a 21-day cycle.
Drug: ABT-263
Experimental
Navitoclax 21/21 Day Cycle: 250 mg
Navitoclax 250 mg administered for 21 consecutive days to complete a 21-day cycle.
Drug: ABT-263
Experimental
Navitoclax 21/21 Day Cycle: 300 mg
Navitoclax 300 mg administered for 21 consecutive days to complete a 21-day cycle.
Drug: ABT-263
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).
Drug: ABT-263
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).
Drug: ABT-263

Interventions

DrugABT-263
Tablet; Oral
Also known as: Navitoclax

What researchers measure

Primary outcomes

Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An SAE is one that: results in death, hospitalization, prolongation of hospitalization, or persistent or significant disability/incapacity; is life-threatening, a congenital anomaly, or other important medical event. Events were graded as 1=mild, 2=moderate, 3=severe, 4=life-threatening, or 5=death. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A treatment-emergent adverse event is defined as any adverse event with onset or worsening reported by a subject from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug administration. Deaths category included non treatment emergent deaths.
Time frame: 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.
Phase 1: Number of Participants With DLTs in the Dose Escalation Phase
DLTs were graded according to NCI CTCAE version 3.0 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life threatening; grade 5=death). Any of the following events, considered possibly or probably related to the administration of navitoclax, were considered a DLT: Grade 4 thrombocytopenia (\< 25,000/mm\^3); platelet counts \< 25,000/mm\^3, Grade 2 or higher bleeding associated with thrombocytopenia; all other Grade 3, 4 or 5 adverse events were considered a DLT. Exceptions included: Grade 3, 4 febrile neutropenia less than 7 days; Grade 3, 4 leukopenia; Grade 3, 4 lymphopenia; Grade 3 nausea, vomiting and/or diarrhea unless unresponsive to treatment; Grade 2 toxicity that requires dose modification or delay of \> 1 week.
Time frame: Cycle 1 (Up to 21 days) plus 7 days
Phase 1: Maximum Tolerated Dose (MTD) in the Dose Escalation Phase
The MTD was defined as the dose at which 30% of participants experienced a DLT during the first cycle. DLTs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life threatening; grade 5=death). Any of the following events, considered possibly or probably related to the administration of navitoclax, were considered a DLT: Grade 4 thrombocytopenia (\< 25,000/mm\^3); platelet counts \< 25,000/mm\^3, Grade 2 or higher bleeding associated with thrombocytopenia; all other Grade 3, 4 or 5 adverse events were considered a DLT. Exceptions included: Grade 3, 4 febrile neutropenia less than 7 days; Grade 3, 4 leukopenia; Grade 3, 4 lymphopenia; Grade 3 nausea, vomiting and/or diarrhea unless unresponsive to treatment; Grade 2 toxicity that requires dose modification or delay of \> 1 week.
Time frame: Cycle 1 (Up to 21 days) plus 7 days
Phase 1: Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase
The RPTD was determined based on observed DLTs and/or determination of the MTD in phase 1. (See Outcome Measures 2 and 3 above for definition of DLT and MTD.)
Time frame: Cycle 1 (Up to 21 days) plus 7 days
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax
Time frame: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: Maximum Observed Plasma Concentration (Cmax)
Time frame: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 8 (AUC8)
Time frame: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 24 (AUC24)
The AUC24 was derived and reported from Cycle 1 Day 1 values and Cycle 1 Day 14 values; the pre-dose value taken on Day 14 was utilized as 24-hour timepoint on Day 14 to generate AUC24 for Day 14.
Time frame: 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
Phase 1: Cmax/Dose
Time frame: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: AUC8/Dose
Time frame: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: AUC24/Dose
The AUC24 was derived and reported from Cycle 1 Day 1 values and Cycle 1 Day 14 values; the pre-dose value taken on Day 14 was utilized as 24-hour timepoint on Day 14 to generate AUC24 for Day 14.
Time frame: 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
Phase 1: Terminal Phase Elimination Rate Constant (β) for Navitoclax
Time frame: Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: Terminal Phase Elimination Half-life (t1/2) of Navitoclax
For t1/2, the harmonic mean and psuedo-standard deviation are used.
Time frame: Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 2: Number of Participants With TEAEs, SAEs, and Discontinuations Due to AEs
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An SAE is one that: results in death, hospitalization, prolongation of hospitalization, or persistent or significant disability/incapacity; is life-threatening, a congenital anomaly, or other important medical event. Events were graded as 1=mild, 2=moderate, 3=severe, 4=life-threatening, or 5=death. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A treatment-emergent adverse event is defined as any adverse event with onset or worsening reported by a subject from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug administration. Deaths category included non treatment emergent deaths.
Time frame: 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.
Phase 2: Dose-Normalized Plasma Concentrations After Navitoclax Once Daily Dosing
Time frame: 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

Results

Posted Jun 13, 2023

Participant flow

Participant flow — Overall Study
Milestone	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg	Phase 2: Navitoclax 100 mg	Phase 2: Navitoclax 250 mg
Started	3	6	3	3	3	4	3	4	4	27
Completed	0	0	0	0	0	0	0	0	0	0
Not completed	3	6	3	3	3	4	3	4	4	27
Withdrew: Withdrawal by subject	0	1	1	0	0	0	0	0	1	6
Withdrew: Other, not specified	0	1	1	0	0	1	0	0	0	4
Withdrew: Adverse event	1	2	0	1	1	1	2	1	1	6
Withdrew: Progressive disease clinical	0	0	0	0	0	0	0	0	1	7
Withdrew: Progressive disease clinical national cancer institute	1	1	0	0	0	1	0	0	0	0
Withdrew: Progressive disease other	1	1	0	1	1	1	0	2	0	0
Withdrew: No reason given	0	0	1	1	1	0	1	1	1	4

Outcome measures

PrimaryPhase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to Adverse Events (AEs)

An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An SAE is one that: results in death, hospitalization, prolongation of hospitalization, or persistent or significant disability/incapacity; is life-threatening, a congenital anomaly, or other important medical event. Events were graded as 1=mild, 2=moderate, 3=severe, 4=life-threatening, or 5=death. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A treatment-emergent adverse event is defined as any adverse event with onset or worsening reported by a subject from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug administration. Deaths category included non treatment emergent deaths.

Time frame:: 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.
Reported as:: Count of participants · Participants

Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to Adverse Events (AEs)
Participants	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg
Any AE	3	6	3	3	3	4	3	4
Any AE at least possibly related to navitoclax	3	4	3	3	3	4	3	4
Any AE with NCI CTCAE Grade ≥ 3	2	4	3	2	2	4	3	4
Any AE with NCI CTCAE Grade 3 or 4	2	4	3	2	2	4	3	4
Any SAE	2	4	2	2	2	4	2	3
Any AE leading to navitoclax discontinuation	1	2	0	1	2	1	2	1
Any AE leading to navitoclax dose reduction	0	1	1	2	0	1	2	0
Any AE leading to navitoclax interruption	0	4	3	2	1	4	3	4
Any AE leading to dose delay	2	3	1	2	0	0	0	2
Any dose limiting toxicity (DLT)	0	2	0	2	0	2	2	2
Any fatal AE	0	1	0	0	1	0	0	0
Deaths	0	1	0	0	1	0	0	0

PrimaryPhase 1: Number of Participants With DLTs in the Dose Escalation Phase

DLTs were graded according to NCI CTCAE version 3.0 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life threatening; grade 5=death). Any of the following events, considered possibly or probably related to the administration of navitoclax, were considered a DLT: Grade 4 thrombocytopenia (\< 25,000/mm\^3); platelet counts \< 25,000/mm\^3, Grade 2 or higher bleeding associated with thrombocytopenia; all other Grade 3, 4 or 5 adverse events were considered a DLT. Exceptions included: Grade 3, 4 febrile neutropenia less than 7 days; Grade 3, 4 leukopenia; Grade 3, 4 lymphopenia; Grade 3 nausea, vomiting and/or diarrhea unless unresponsive to treatment; Grade 2 toxicity that requires dose modification or delay of \> 1 week.

Time frame:: Cycle 1 (Up to 21 days) plus 7 days
Reported as:: Count of participants · Participants

Phase 1: Number of Participants With DLTs in the Dose Escalation Phase
Participants	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg
Phase 1: Number of Participants With DLTs in the Dose Escalation Phase	0	1	0	2	0	1	1	1

PrimaryPhase 1: Maximum Tolerated Dose (MTD) in the Dose Escalation Phase

The MTD was defined as the dose at which 30% of participants experienced a DLT during the first cycle. DLTs were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 (grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life threatening; grade 5=death). Any of the following events, considered possibly or probably related to the administration of navitoclax, were considered a DLT: Grade 4 thrombocytopenia (\< 25,000/mm\^3); platelet counts \< 25,000/mm\^3, Grade 2 or higher bleeding associated with thrombocytopenia; all other Grade 3, 4 or 5 adverse events were considered a DLT. Exceptions included: Grade 3, 4 febrile neutropenia less than 7 days; Grade 3, 4 leukopenia; Grade 3, 4 lymphopenia; Grade 3 nausea, vomiting and/or diarrhea unless unresponsive to treatment; Grade 2 toxicity that requires dose modification or delay of \> 1 week.

Time frame:: Cycle 1 (Up to 21 days) plus 7 days
Reported as:: Number · mg

Phase 1: Maximum Tolerated Dose (MTD) in the Dose Escalation Phase
mg	Participants Receiving 14/21-Day Dosing Schedule in Phase 1	Participants Receiving 21/21-Day Dosing Schedule in Phase 1
Phase 1: Maximum Tolerated Dose (MTD) in the Dose Escalation Phase	200	250

PrimaryPhase 1: Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase

The RPTD was determined based on observed DLTs and/or determination of the MTD in phase 1. (See Outcome Measures 2 and 3 above for definition of DLT and MTD.)

Time frame:: Cycle 1 (Up to 21 days) plus 7 days
Reported as:: Number · mg

Phase 1: Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase
mg	Participants Receiving 14/21-Day Dosing Schedule in Phase 1	Participants Receiving 21/21-Day Dosing Schedule in Phase 1
Phase 1: Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase	250	250

PrimaryPhase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax

Time frame:: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Reported as:: Mean · hours

Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax
hours	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg
Cycle 1 Day 1	6.0 ± 2.0	5.9 ± 1.6	6.7 ± 1.2	7.3 ± 1.2	7.3 ± 1.2	6.5 ± 1.0	6.7 ± 2.3	7.5 ± 1.0
Cycle 1 Day 14	4.3 ± 1.5	3.5 ± 2.8	6.8 ± 1.5	5.7 ± 0.4	5.8 ± 1.8	6.7 ± 1.2	6.9 ± 1.8	7.3 ± 1.2

PrimaryPhase 1: Maximum Observed Plasma Concentration (Cmax)

Time frame:: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Reported as:: Mean · μg/mL

Phase 1: Maximum Observed Plasma Concentration (Cmax)
μg/mL	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg
Cycle 1 Day 1	0.25 ± 0.14	1.19 ± 0.37	2.60 ± 1.54	5.19 ± 2.70	2.24 ± 0.98	2.73 ± 0.82	2.59 ± 1.60	3.30 ± 1.20
Cycle 1 Day 14	0.42 ± 0.17	1.87 ± 0.71	4.44 ± 3.59	3.21 ± 0.12	2.68 ± 1.11	3.46 ± 1.57	3.74 ± 1.19	3.11 ± 2.26

PrimaryPhase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 8 (AUC8)

Time frame:: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Reported as:: Mean · μg•hr/mL

Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 8 (AUC8)
μg•hr/mL	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg
Cycle 1 Day 1	1.0 ± 0.65	5.7 ± 2.7	10.6 ± 4.0	19.8 ± 14.0	12.0 ± 4.2	12.3 ± 3.0	12.0 ± 9.2	14.3 ± 5.7
Cycle 1 Day 14	2.2 ± 0.95	11.1 ± 2.7	24.2 ± 18.1	17.8 ± 2.3	15.7 ± 6.8	18.4 ± 8.7	24.4 ± 5.7	21.6 ± 15.6

PrimaryPhase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 24 (AUC24)

The AUC24 was derived and reported from Cycle 1 Day 1 values and Cycle 1 Day 14 values; the pre-dose value taken on Day 14 was utilized as 24-hour timepoint on Day 14 to generate AUC24 for Day 14.

Time frame:: 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
Reported as:: Mean · μg•hr/mL

Phase 1: Area Under the Plasma Concentration-Time Curve From Time 0 to Hour 24 (AUC24)
μg•hr/mL	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg
Cycle 1 Day 1	2.7 ± 1.0	15.0 ± 3.2	34.0 ± 13.8	67.8 ± 27.7	37.5 ± 16.0	44.0 ± 18.7	49.5 ± 12.3	52.9 ± 20.1
Cycle 1 Day 14	5.5 ± 2.7	30.9 ± 7.7	68.7 ± 42.9	50.6 ± 0.36	43.5 ± 16.6	56.2 ± 28.6	72.7 ± 14.4	64.8 ± 49.4

PrimaryPhase 1: Cmax/Dose

Time frame:: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Reported as:: Mean · ng/mL/mg

Phase 1: Cmax/Dose
ng/mL/mg	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg
Cycle 1 Day 1	24.5 ± 13.9	10.7 ± 3.4	13.0 ± 7.7	20.8 ± 10.8	17.9 ± 7.9	13.7 ± 4.1	10.4 ± 6.4	11.0 ± 4.0
Cycle 1 Day 14	42.3 ± 16.6	17.0 ± 6.4	22.2 ± 17.9	12.8 ± 0.48	21.4 ± 8.9	17.3 ± 7.9	15.0 ± 4.8	10.4 ± 7.5

PrimaryPhase 1: AUC8/Dose

Time frame:: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Reported as:: Mean · ng•hr/mL/mg

Phase 1: AUC8/Dose
ng•hr/mL/mg	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg
Cycle 1 Day 1	99.9 ± 65.0	52.0 ± 24.7	53.1 ± 20.1	79.2 ± 56.1	95.8 ± 33.5	61.3 ± 14.9	47.9 ± 36.8	47.6 ± 18.8
Cycle 1 Day 14	215.0 ± 95.1	101.0 ± 24.7	121.0 ± 90.4	71.3 ± 9.1	125.0 ± 54.1	92.1 ± 43.3	97.7 ± 22.6	72.0 ± 51.9

PrimaryPhase 1: AUC24/Dose

The AUC24 was derived and reported from Cycle 1 Day 1 values and Cycle 1 Day 14 values; the pre-dose value taken on Day 14 was utilized as 24-hour timepoint on Day 14 to generate AUC24 for Day 14.

Time frame:: 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
Reported as:: Mean · ng•hr/mL/mg

Phase 1: AUC24/Dose
ng•hr/mL/mg	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg
Cycle 1 Day 1	268 ± 100.0	136 ± 28.8	170 ± 69.2	271 ± 111.0	300 ± 128.0	220 ± 93.6	198 ± 49.3	176 ± 67.0
Cycle 1 Day 14	546 ± 267.0	281 ± 69.9	344 ± 215.0	202 ± 1.5	348 ± 133.0	281 ± 143.0	291 ± 57.5	216.0 ± 165.0

PrimaryPhase 1: Terminal Phase Elimination Rate Constant (β) for Navitoclax

Time frame:: Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
Reported as:: Mean · 1/H

Phase 1: Terminal Phase Elimination Rate Constant (β) for Navitoclax
1/H	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg
Phase 1: Terminal Phase Elimination Rate Constant (β) for Navitoclax	0.072 ± 0.029	0.077 ± 0.006	0.067 ± 0.030	0.059 ± NA	—	0.066 ± 0.025	—	0.039 ± NA

PrimaryPhase 1: Terminal Phase Elimination Half-life (t1/2) of Navitoclax

For t1/2, the harmonic mean and psuedo-standard deviation are used.

Time frame:: Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
Reported as:: Mean · hours

Phase 1: Terminal Phase Elimination Half-life (t1/2) of Navitoclax
hours	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg
Phase 1: Terminal Phase Elimination Half-life (t1/2) of Navitoclax	9.62 ± 4.18	8.99 ± 0.66	10.41 ± 5.21	11.72 ± NA	—	10.51 ± 4.01	—	17.88 ± NA

PrimaryPhase 2: Number of Participants With TEAEs, SAEs, and Discontinuations Due to AEs

Time frame:: 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.
Reported as:: Count of participants · Participants

Phase 2: Number of Participants With TEAEs, SAEs, and Discontinuations Due to AEs
Participants	Phase 2: Navitoclax 100 mg	Phase 2: Navitoclax 250 mg
Any AE	4	27
Any AE at least possibly related to navitoclax	4	26
Any AE with NCI CTCAE Grade ≥ 3	3	23
Any AE with NCI CTCAE Grade 3 or 4	3	23
Any SAE	1	12
Any AE leading to navitoclax discontinuation	1	9
Any AE leading to navitoclax dose reduction	1	10
Any AE leading to navitoclax interruption	2	16
Any AE leading to navitoclax dose delay	2	5
Any fatal AE	0	1
Deaths	1	8

PrimaryPhase 2: Dose-Normalized Plasma Concentrations After Navitoclax Once Daily Dosing

Time frame:: 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
Reported as:: Mean · (ng/mL)/mg

Phase 2: Dose-Normalized Plasma Concentrations After Navitoclax Once Daily Dosing
(ng/mL)/mg	Participants Receiving Navitoclax QD Dosing in Phase 2
Cycle 1 Day 1: 4-8 h postdose	9.49 ± 4.80
Cycle 1 Day 15: predose	9.64 ± 5.85
Cycle 3 Day 1: predose	9.84 ± 3.55
Cycle 3 Day 1: 4-8 h postdose	15.2 ± 8.04
Cycle 5 Day 1: predose	9.84 ± 4.38
Cycle 5 Day 1: 4-8 h postdose	15.7 ± 8.28
Cycle 7 Day 1: predose	10.4 ± 5.26
Cycle 7 Day 1: 4-8 h postdose	15.9 ± 9.14
Cycle 9 Day 1: predose	11.4 ± 9.68
Cycle 9 Day 1: 4-8 h postdose	13.5 ± 6.41

Adverse events

Collected over Adverse events: 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. Participants enrolled in Phase 2 received a mean of 15.6 treatment cycles.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Navitoclax 14/21 Day Cycle: 10 mg	0/3 (0%)	2/3 (66.7%)	3/3 (100%)
Navitoclax 14/21 Day Cycle: 110 mg	1/6 (16.7%)	4/6 (66.7%)	6/6 (100%)
Navitoclax 14/21 Day Cycle: 200 mg	0/3 (0%)	2/3 (66.7%)	3/3 (100%)
Navitoclax 14/21 Day Cycle: 250 mg	0/3 (0%)	2/3 (66.7%)	3/3 (100%)
Navitoclax 21/21 Day Cycle: 125 mg	1/3 (33.3%)	2/3 (66.7%)	3/3 (100%)
Navitoclax 21/21 Day Cycle: 200 mg	0/4 (0%)	4/4 (100%)	4/4 (100%)
Navitoclax 21/21 Day Cycle: 250 mg	0/3 (0%)	2/3 (66.7%)	3/3 (100%)
Navitoclax 21/21 Day Cycle: 300 mg	0/4 (0%)	3/4 (75%)	4/4 (100%)
Phase 2: Navitoclax 100 mg	1/4 (25%)	1/4 (25%)	4/4 (100%)
Phase 2: Navitoclax 250 mg	8/27 (29.6%)	12/27 (44.4%)	27/27 (100%)

Most frequent serious events

Showing 10 of 56

Most frequent serious events
Event	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg	Phase 2: Navitoclax 100 mg	Phase 2: Navitoclax 250 mg
HYPERCALCAEMIAMetabolism and nutrition disorders	0/3	0/6	0/3	0/3	0/3	0/4	0/3	2/4	0/4	0/27
NEUTROPENIABlood and lymphatic system disorders	1/3	0/6	0/3	0/3	0/3	1/4	0/3	1/4	0/4	0/27
CONSTIPATIONGastrointestinal disorders	0/3	0/6	0/3	0/3	1/3	0/4	0/3	0/4	0/4	0/27
APPENDICITISInfections and infestations	0/3	0/6	0/3	1/3	0/3	0/4	0/3	0/4	0/4	0/27
CELLULITISInfections and infestations	0/3	0/6	0/3	0/3	1/3	0/4	0/3	0/4	0/4	0/27
LOWER RESPIRATORY TRACT INFECTIONInfections and infestations	1/3	0/6	0/3	0/3	1/3	1/4	0/3	0/4	0/4	0/27
PHARYNGITISInfections and infestations	0/3	0/6	1/3	0/3	0/3	0/4	0/3	0/4	0/4	0/27
PNEUMONIAInfections and infestations	0/3	1/6	1/3	1/3	0/3	0/4	1/3	0/4	0/4	2/27
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHYInfections and infestations	0/3	0/6	0/3	0/3	1/3	0/4	0/3	0/4	0/4	0/27
PSEUDOMONAL SEPSISInfections and infestations	0/3	1/6	0/3	0/3	1/3	0/4	0/3	0/4	0/4	0/27

Most frequent other events

Showing 10 of 204

Most frequent other events
Event	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg	Phase 2: Navitoclax 100 mg	Phase 2: Navitoclax 250 mg
DIARRHOEAGastrointestinal disorders	1/3	4/6	3/3	3/3	2/3	3/4	3/3	3/4	4/4	20/27
NAUSEAGastrointestinal disorders	1/3	3/6	2/3	2/3	3/3	2/4	2/3	2/4	2/4	13/27
SINUSITISInfections and infestations	1/3	1/6	0/3	3/3	0/3	1/4	0/3	1/4	0/4	1/27
THROMBOCYTOPENIABlood and lymphatic system disorders	0/3	1/6	2/3	2/3	0/3	1/4	0/3	1/4	1/4	13/27
EAR PAINEar and labyrinth disorders	0/3	0/6	2/3	0/3	0/3	0/4	0/3	0/4	0/4	0/27
ABDOMINAL PAINGastrointestinal disorders	2/3	1/6	0/3	0/3	0/3	1/4	0/3	0/4	1/4	2/27
VOMITINGGastrointestinal disorders	1/3	0/6	1/3	1/3	2/3	2/4	1/3	1/4	1/4	5/27
FATIGUEGeneral disorders	0/3	3/6	2/3	2/3	0/3	2/4	2/3	1/4	1/4	10/27
NASOPHARYNGITISInfections and infestations	0/3	0/6	1/3	2/3	1/3	1/4	1/3	0/4	1/4	5/27
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations	1/3	1/6	1/3	2/3	1/3	2/4	1/3	0/4	0/4	8/27

Baseline characteristics

Age, Customized
Age, Customized(Participants)	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg	Phase 2: Navitoclax 100 mg	Phase 2: Navitoclax 250 mg	Total
< 65 years	1	0	1	1	1	3	0	1	1	10	19
>= 65 years	2	6	2	2	2	1	3	3	3	17	41

Sex: Female, Male
Sex: Female, Male(Participants)	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg	Phase 2: Navitoclax 100 mg	Phase 2: Navitoclax 250 mg	Total
Female	2	1	0	1	2	1	0	3	0	8	18
Male	1	5	3	2	1	3	3	1	4	19	42

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg	Phase 2: Navitoclax 100 mg	Phase 2: Navitoclax 250 mg	Total
White	3	6	2	3	2	3	2	3	4	24	52
Black	0	0	0	0	0	0	0	0	0	1	1
American Indian/Alaska Native	0	0	0	0	0	0	0	0	0	0	0
Native Hawaiian or Pacific Islander	0	0	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	0	0	1	1
Mixed	0	0	0	0	0	1	0	0	0	0	1
Other, Not Specified	0	0	1	0	1	0	1	1	0	1	5
Missing	0	0	0	0	0	0	0	0	0	0	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Navitoclax 14/21 Day Cycle: 10 mg	Navitoclax 14/21 Day Cycle: 110 mg	Navitoclax 14/21 Day Cycle: 200 mg	Navitoclax 14/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 125 mg	Navitoclax 21/21 Day Cycle: 200 mg	Navitoclax 21/21 Day Cycle: 250 mg	Navitoclax 21/21 Day Cycle: 300 mg	Phase 2: Navitoclax 100 mg	Phase 2: Navitoclax 250 mg	Total
Hispanic	0	0	0	0	0	0	0	0	0	0	0
No Ethnicity	3	6	3	3	3	4	3	4	4	27	60

Study locations

10 sites

Moores Cancer Center at UC San Diego /ID# 5566
La Jolla, California 92093, United States
Dana-Farber Cancer Institute /ID# 5547
Boston, Massachusetts 02215, United States
University of Nebraska Medical Center /ID# 12261
Omaha, Nebraska 68198, United States
North Shore University Hospital /ID# 12267
New Hyde Park, New York 11040, United States
University of Texas MD Anderson Cancer Center /ID# 5575
Houston, Texas 77030, United States
Northwest Medical Specialties - Tacoma /ID# 26428
Tacoma, Washington 98405, United States
Peter MacCallum Cancer Ctr /ID# 6583
Melbourne, Victoria 3000, Australia
The Royal Melbourne Hospital /ID# 5576
Parkville, Victoria 3050, Australia
Universitaetsklinikum Koeln /ID# 5924
Köln, Nordrhein-Westfalen 50937, Germany
Leicester Royal Infirmary /ID# 15081
Leicester, England LE1 5WW, United Kingdom

References and documents

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. PubMed 22184378 ↗

Study documents

Study protocol · Sep 3, 2020
Statistical analysis plan · Apr 27, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

Supporting information: Study protocol, Sap, Csr

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 13, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00481091
Lead sponsor: AbbVie
Collaborators: Genentech, Inc.
Responsible party: Sponsor
First posted: Jun 1, 2007
Start date: Jul 25, 2007
Primary completion: May 12, 2022
Completion: May 12, 2022
Results posted: Jun 13, 2023
Last update: Jun 13, 2023

Study contacts

ABBVIE INC.

study director · AbbVie

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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