Chronic Lymphocytic LeukemiaPhase 1/2NCT00481091
A Study of ABT-263 in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia
A Phase 1/2 study testing ABT-263 in people with Chronic Lymphocytic Leukemia, run by AbbVie at 10 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- ABT-263
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 10 sitesin 4 countries
- Study dates
- 25 Jul 2007to 12 May 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
United States6 sites
Dana-Farber Cancer Institute /ID# 5547
Boston, Massachusetts, 02215
University of Texas MD Anderson Cancer Center /ID# 5575
Houston, Texas, 77030
Moores Cancer Center at UC San Diego /ID# 5566
La Jolla, California, 92093
North Shore University Hospital /ID# 12267
New Hyde Park, New York, 11040
University of Nebraska Medical Center /ID# 12261
Omaha, Nebraska, 68198
Northwest Medical Specialties - Tacoma /ID# 26428
Tacoma, Washington, 98405
Australia2 sites
Peter MacCallum Cancer Ctr /ID# 6583
Melbourne, Victoria, 3000
The Royal Melbourne Hospital /ID# 5576
Parkville, Victoria, 3050
Germany1 site
Universitaetsklinikum Koeln /ID# 5924
Cologne, North Rhine-Westphalia, 50937
United Kingdom1 site
Leicester Royal Infirmary /ID# 15081
Leicester, England, LE1 5WW
About this study
Official title: A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABT-263 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia
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
- Chronic Lymphocytic Leukemia
- Being tested
- ABT-263
- Keywords
- Chronic Lymphocytic Leukemia (CLL), Navitoclax, ABT-263, Cancer
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABT-263Drug
Also called Navitoclax
Tablet; Oral
| Study group | Role | What they receive |
|---|---|---|
| Navitoclax 14/21 Day Cycle: 10 mg | Experimental | Navitoclax 10 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. Receives: Drug: ABT-263 |
| Navitoclax 14/21 Day Cycle: 110 mg | Experimental | Navitoclax 110 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. Receives: Drug: ABT-263 |
| Navitoclax 14/21 Day Cycle: 200 mg | Experimental | Navitoclax 200 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. Receives: Drug: ABT-263 |
| Navitoclax 14/21 Day Cycle: 250 mg | Experimental | Navitoclax 250 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. Receives: Drug: ABT-263 |
| Navitoclax 21/21 Day Cycle: 125 mg | Experimental | Navitoclax 125 mg administered for 21 consecutive days to complete a 21-day cycle. Receives: Drug: ABT-263 |
| Navitoclax 21/21 Day Cycle: 200 mg | Experimental | Navitoclax 200 mg administered for 21 consecutive days to complete a 21-day cycle. Receives: Drug: ABT-263 |
| Navitoclax 21/21 Day Cycle: 250 mg | Experimental | Navitoclax 250 mg administered for 21 consecutive days to complete a 21-day cycle. Receives: Drug: ABT-263 |
| Navitoclax 21/21 Day Cycle: 300 mg | Experimental | Navitoclax 300 mg administered for 21 consecutive days to complete a 21-day cycle. Receives: Drug: ABT-263 |
| Phase 2: Navitoclax 100 mg | Experimental | Navitoclax 100 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s). Receives: Drug: ABT-263 |
| Phase 2: Navitoclax 250 mg | Experimental | Navitoclax 250 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s). Receives: Drug: ABT-263 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.)
Measured: Cycle 1 (Up to 21 days) plus 7 days
Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax
Measured: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: Maximum Observed Plasma Concentration (Cmax)
Measured: 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)
Measured: 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.
Measured: 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
Measured: Cycle 1 Days 1 and 14: pre-dose, 2, 4, 6, 8 hours post-dose
Phase 1: AUC8/Dose
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2007 (estimated)
- Study start25 Jul 2007
- Primary completion12 May 2022
- Study completion12 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- ABBVIE INC., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00481091
- Sponsor's protocol ID
- M06-873
- Other IDs
- 2007-002143-25
- Status last verified
- Jun 2023
- First submitted
- 30 May 2007
- Last updated
- 13 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
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 at a glance
From the registry record, last updated by the sponsor on 13 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a Study Evaluating the Safety, Pharmacokinetics, and Efficacy of ABT-263 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT00481091
- Acronym / sponsor ID
- M06-873
- Conditions
- Chronic Lymphocytic Leukemia
- Keywords
- Chronic Lymphocytic Leukemia (CLL), Navitoclax, ABT-263, Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc.
- Study start
- 25 Jul 2007 (actual)
- Primary completion
- 12 May 2022 (actual)
- Study completion
- 12 May 2022 (actual)
- First posted
- 1 Jun 2007 (estimated)
- Results
- Posted 13 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Navitoclax 14/21 Day Cycle: 10 mg | Experimental | Drug: ABT-263Navitoclax 10 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. |
| Navitoclax 14/21 Day Cycle: 110 mg | Experimental | Drug: ABT-263Navitoclax 110 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. |
| Navitoclax 14/21 Day Cycle: 200 mg | Experimental | Drug: ABT-263Navitoclax 200 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. |
| Navitoclax 14/21 Day Cycle: 250 mg | Experimental | Drug: ABT-263Navitoclax 250 mg administered for 14 consecutive days followed by 7 days off drug to complete a 21-day cycle. |
| Navitoclax 21/21 Day Cycle: 125 mg | Experimental | Drug: ABT-263Navitoclax 125 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Navitoclax 21/21 Day Cycle: 200 mg | Experimental | Drug: ABT-263Navitoclax 200 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Navitoclax 21/21 Day Cycle: 250 mg | Experimental | Drug: ABT-263Navitoclax 250 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Navitoclax 21/21 Day Cycle: 300 mg | Experimental | Drug: ABT-263Navitoclax 300 mg administered for 21 consecutive days to complete a 21-day cycle. |
| Phase 2: Navitoclax 100 mg | Experimental | Drug: ABT-263Navitoclax 100 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s). |
| Phase 2: Navitoclax 250 mg | Experimental | Drug: ABT-263Navitoclax 250 mg in participants with CLL who had relapsed following any (but no more than 5) prior myelosuppressive/chemotherapy treatment regimen(s). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABT-263Also: NavitoclaxTablet; Oral | Drug | 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 |
Primary outcome
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to Adverse Events (AEs)
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.
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.
Phase 1: Number of Participants With DLTs in the Dose Escalation Phase
Time frame: Cycle 1 (Up to 21 days) plus 7 days
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.
Phase 1: Maximum Tolerated Dose (MTD) in the Dose Escalation Phase
Time frame: Cycle 1 (Up to 21 days) plus 7 days
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.
Phase 1: Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase
Time frame: Cycle 1 (Up to 21 days) plus 7 days
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.)
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)
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
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.
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
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
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.
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
Time frame: Cycle 1 Day 1: pre-dose, 2, 4, 6, 8 hours post-dose
For t1/2, the harmonic mean and psuedo-standard deviation are used.
Phase 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.
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.
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 and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22184378Roberts 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: 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.
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RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ABBVIE INC. study director
AbbVie
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ABT-263 in people with Chronic Lymphocytic Leukemia, run by AbbVie at 10 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Australia, Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to Adverse Events (AEs) (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.). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00481091, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2023.