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

Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT00481091
Collaborator
Genentech, Inc. (Industry)
60
10
2
177.6
6
0

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
60 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 25, 2007
Actual Primary Completion Date :
May 12, 2022
Actual Study Completion Date :
May 12, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1: Dose Escalation Portion

Participants will receive escalating doses of ABT-263 to determine the recommended phase 2 dose (RPTD). Eligible participants can continue to receive ABT-263 for 11 years in the extension portion.

Drug: ABT-263
Tablet; Oral
Other Names:
  • Navitoclax
  • Experimental: Phase 2a: Dose Expansion Portion

    Participants will receive ABT-263 at the RPTD determined in Phase 1 portion. Eligible participants can continue to receive ABT-263 for 11 years in the extension portion.

    Drug: ABT-263
    Tablet; Oral
    Other Names:
  • Navitoclax
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants with Adverse Events [Up to approximately 13 years]

      An adverse event (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. 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.

    2. Number of Participants with Dose Limiting Toxicity (DLT) in the Dose Escalation Phase (Phase 1) [Cycle 1 (Up to 21 days)]

      DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0.

    3. Maximum Tolerated Dose (MTD) in the Dose Escalation Phase (Phase 1) [Cycle 1 (Up to 21 days)]

      The MTD will be determined by using available clinical data during dose escalation in phase 1.

    4. Recommended Phase 2 Dose (RPTD) Determined in the Dose Escalation Phase (Phase 1) [Cycle 1 (Up to 21 days)]

      The RPTD will be determined based on observed dose-limiting toxicities (DLTs) and/or determination of the maximum tolerated dose (MTD) in phase 1.

    5. Maximum Observed Plasma Concentration (Cmax) of Navitoclax (Phase 1) [Up to Day 14]

      Cmax of navitoclax.

    6. Time to Maximum Observed Plasma Concentration (Tmax) of Navitoclax (Phase 1) [Up to Day 14]

      Tmax of navitoclax.

    7. Terminal phase elimination rate constant (β) for Navitoclax (Phase 1) [Day 1]

      Terminal phase elimination rate constant (β) for navitoclax.

    8. Terminal phase elimination half-life (t1/2) of Navitoclax (Phase 1) [Day 1]

      Terminal phase elimination half-life (t1/2) of navitoclax.

    9. Area Under the Plasma Concentration-time Curve over time from 0 to 24 hours (AUC0-24) of Navitoclax (Phase 1) [Day 1]

      AUC0-24 of navitoclax.

    10. Area Under the Plasma Concentration-time Curve over time from 0 to 8 hours (AUC0-8) of Navitoclax (Phase 1) [Day 14]

      AUC0-8 of navitoclax.

    11. Progression-free Survival (PFS) (Extension Portion) [Up to approximately 13 years]

      PFS defined as the time from the date the participant started study drug to the date the participant experiences an event of disease progression.

    12. Overall Survival (OS) (Extension Portion) [Up to approximately 13 years]

      OS defined as the time from the date the participant started study drug to the date the participant's death.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Relapsed or refractory Chronic Lymphocytic Leukemia and require treatment in opinion of investigator.

    • Eastern Cooperative Oncology Group (ECOG) <= 1.

    • Adequate bone marrow independent of growth factor support, renal and hepatic function per defined laboratory criteria.

    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).

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • AbbVie
    • Genentech, Inc.

    Investigators

    • Study Director: ABBVIE INC., AbbVie

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT00481091
    Other Study ID Numbers:
    • M06-873
    • 2007-002143-25
    First Posted:
    Jun 1, 2007
    Last Update Posted:
    Jul 11, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Keywords provided by AbbVie
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 11, 2022