A Study of the Efficacy of ABT-199 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia With the 17p Deletion

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by AbbVie
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie
ClinicalTrials.gov Identifier:
NCT01889186
First received: June 26, 2013
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

This is a Phase 2, open label, multicenter, study evaluating the efficacy of ABT-199 in approximately 100 relapsed or refractory subjects with CLL harboring 17p13 (TP53 locus) deletion.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
17 p Deletion
Cancer of the Blood and Bone Marrow
Drug: ABT-199
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label Study of the Efficacy of ABT-199 (GDC-0199) in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia Harboring the 17p Deletion

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Efficacy will be measured by overall response rate (ORR) [ Time Frame: Measured up to 2 years after the last subject has enrolled on the study. ] [ Designated as safety issue: No ]
    To evaluate the efficacy of ABT-199 monotherapy in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion.


Secondary Outcome Measures:
  • Complete Remission (CR) rate [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Complete remission rate per Independent Review Committee assessment, will be defined as the proportion of subjects who achieved a CR per the NCI-CWG (National Cancer Institute-Working Group) criteria.

  • Partial Remission (PR) rate [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Partial remission rate per Independent Review Committee assessment, will be defined as the proportion of subjects who achieved a PR per the NCI-CWG criteria.

  • Duration of response [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Duration of response will be defined as the number of days from the date of first response (Complete Remission or Partial Remission) per Independent Review Committee (IRC) assessment to the earliest recurrence or Progressive Disease per IRC assessment.

  • Progression-free survival [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Progression-free survival will be defined as the number of days from the date of first dose to the date of earliest disease progression (per Independent Review Committee assessment) or death.

  • Time to progression [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study ] [ Designated as safety issue: No ]
    Time to progression will be defined as the number of days from the date of first dose to the date of earliest disease progression (per Independent Review Committee assessment).

  • Overall survival [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    Overall survival will be defined as the number of days from the date of first dose to the date of death for all dosed subjects.

  • Percent of subjects who move on to stem cell transplant [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ] [ Designated as safety issue: No ]
    The percent of subjects who move on to stem cell transplant will be summarized and the 95% confidence interval based on the binomial distribution will be provided.

  • Number of subjects with adverse events [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ] [ Designated as safety issue: Yes ]
    Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study.

  • Change in physical exam findings, including vital signs [ Time Frame: Measured from Day -1 up to 5 years after the last subject has enrolled in the study. ] [ Designated as safety issue: Yes ]
    Body temperature, weight, blood pressure, heart rate.

  • Change in clinical laboratory test results [ Time Frame: Measured from Day -1 up to 5 years after the last subject has enrolled in the study. ] [ Designated as safety issue: Yes ]
    Chemistry, hematology, urinalysis, viral serologies.

  • Change in cardiac assessment findings [ Time Frame: Measured from Day -1 up to 2 years after the last subject has enrolled in the study. ] [ Designated as safety issue: Yes ]
    Electrocardiogram and Multi Gated Acquisition Scan and/or Echocardiogram.

  • Percentage of subjects with adverse events [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ] [ Designated as safety issue: Yes ]
    Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study.


Estimated Enrollment: 100
Study Start Date: June 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm
Single arm
Drug: ABT-199
Tablet

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject must be greater than or equal to 18 years of age.
  • Subject must have diagnosis of CLL that meets published 2008 IWCLL NCI-WG (International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute-Working Group) criteria.

    • Subject has an indication for treatment according to the 2008 IWCLL NCI WG criteria;
    • Subject has clinically measurable disease;
    • Subject must have relapsed or be refractory after receiving at least one prior line of therapy (a line of therapy is defined as completing at least 2 cycles of treatment for a given line of therapy);
    • Subjects must have 17p deletion, assessed by central laboratory, and determined by FISH using the Vysis CLL probe kit.
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
  • Subject must have adequate bone marrow function at Screening as follows:

    • Absolute Neutrophil Count (ANC) greater than or equal to 1000/μL, or
    • For subjects with an ANC less than 1000/μL at Screening and bone marrow heavily infiltrated with underlying disease (approximately 80% or more), granulocyte-colony stimulating factor (G-CSF) may be administered after Screening and prior to the first dose of ABT-199 to achieve the ANC eligibility criteria (greater than or equal to 1000/μL);
    • Platelets greater than 40,000/mm3 (entry platelet count must be independent of transfusion within 14 days of Screening);
    • Hemoglobin greater than or equal to 8.0 g/dL.
  • Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening as follows:

    • Activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5 × the upper limit of normal;
    • Calculated creatinine clearance greater than 50 mL/min using the Cockcroft-Gault equation or a 24-hour urine collection for Creatinine Clearance;
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3.0 × the upper normal limit of institution's normal range; Bilirubin less than or equal to 1.5 × upper limit of normal. Subjects with Gilbert's Syndrome may have a bilirubin greater 1.5 × upper limit of normal, per discussion between the investigator and AbbVie medical monitor.
  • For subjects at high risk of tumor lysis syndrome a pre-approval by the AbbVie medical monitor is required prior to enrollment.

Exclusion Criteria:

  • Subject has undergone an allogeneic stem cell transplant.
  • Subject has developed Richter's transformation.
  • Subject has active and uncontrolled autoimmune cytopenias (for 2 weeks), including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura.
  • Subject has previously received ABT-199.
  • Subject has received a biologic agent for anti-neoplastic intent within 8 weeks prior to the first dose of study drug.
  • Subject has received any of the following within 14 days prior to the first dose of study drug, or has not recovered to less than Common Toxicity Criteria (CTC) grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:

    • Any anti-cancer therapy including chemotherapy, or radiotherapy;
    • Investigational therapy, including targeted small molecule agents.
  • Subject has known allergy to both xanthine oxidase inhibitors and rasburicase.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01889186

Contacts
Contact: Cathy Nolan, BS 847-973-2404 cathy.nolan@abbvie.com
Contact: Michael Dawson, BS 847-938-9467 michael.dawson@abbvie.com

  Show 60 Study Locations
Sponsors and Collaborators
AbbVie
Genentech, Inc.
Investigators
Study Director: Elisa Cerri, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT01889186     History of Changes
Other Study ID Numbers: M13-982, 2012-004027-20
Study First Received: June 26, 2013
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
Poland: The Central Register of Clinical Trials
Ukraine: State Pharmacological Center - Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by AbbVie:
Chronic Lymphocytic Leukemia
17 p Deletion

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 22, 2014