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

June 12, 2023 updated by: AbbVie

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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:

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Tablet; Oral
Other Names:
  • Navitoclax
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
Tablet; Oral
Other Names:
  • Navitoclax
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
Tablet; Oral
Other Names:
  • Navitoclax
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
Tablet; Oral
Other Names:
  • Navitoclax
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
Tablet; Oral
Other Names:
  • Navitoclax
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
Tablet; Oral
Other Names:
  • Navitoclax
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
Tablet; Oral
Other Names:
  • Navitoclax
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
Tablet; Oral
Other Names:
  • Navitoclax
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
Tablet; Oral
Other Names:
  • Navitoclax
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
Tablet; Oral
Other Names:
  • Navitoclax

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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
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.
Cycle 1 (Up to 21 days) plus 7 days
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.
Cycle 1 (Up to 21 days) plus 7 days
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.)
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
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
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
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.
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
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
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.
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
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.
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
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.
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AbbVie

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Genentech, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: ABBVIE INC., AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 25, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 12, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 12, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 30, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 30, 2007

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 1, 2007

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 13, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 12, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • M06-873
  • 2007-002143-25 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

IPD Sharing Access Criteria

Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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