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 October 2014 by AbbVie
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie
ClinicalTrials.gov Identifier:
NCT01889186
First received: June 26, 2013
Last updated: October 28, 2014
Last verified: October 2014
  Purpose

This is a Phase 2, open label, multicenter, study evaluating the efficacy and safety of ABT-199 in relapsed or refractory subjects with CLL harboring 17p13 (TP53 locus) deletion. One hundred seven (107) subjects were enrolled in the main cohort, with evaluation of efficacy as the primary objective, and approximately 50 subjects will be enrolled in the safety expansion cohort to evaluate safety and updated tumor lysis syndrome prophylaxis and management measures. Enrollment into the main cohort is closed. Enrollment into the safety expansion cohort is ongoing.


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) (Main Cohort) [ 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. (Main Cohort)

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

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

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

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

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


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 (Main Cohort) [ 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. (Main Cohort)

  • Change in physical exam findings, including vital signs (Main Cohort) [ 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. (Main Cohort)

  • Change in clinical laboratory test results (Main Cohort) [ 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. (Main Cohort)

  • Change in cardiac assessment findings (Main Cohort) [ 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. (Main Cohort)

  • Percentage of subjects with adverse events (Main Cohort) [ 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. (Main Cohort)

  • Overall Response Rate (ORR) (Expanded Safety Cohort) [ Time Frame: Measured up to 2 years after the last subject has enrolled on thestudy. ] [ 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. (Expanded Safety Cohort)


Estimated Enrollment: 150
Study Start Date: June 2013
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: December 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 Modified IWCLL NCI-WG (International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute-Working Group) Guidelines.

    • Subject has an indication for treatment according to the 2008 Modified IWCLL NCI WG Guidelines;
    • Subject has clinically measurable disease (lymphocytosis > 5 × 10^9/L and/or palpable and measurable nodes by physical exam and/or organomegally assessed by physical exam);
    • Subject must be refractory or have relapsed after receiving at least one prior line of therapy (subjects that have progressed after 1 cycle of treatment or have completed at least 2 cycles of treatment for a given line of therapy);
    • Subjects must have 17p deletion, assessed by local laboratory (in bone marrow or peripheral blood) or assessed by central laboratory (peripheral blood).
  • 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 (unless cytopenia is clearly due to marrow involvement of CLL), growth factor support 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 30,000/mm3 (without transfusion support within 14 days of Screening, without evidence of mucosal bleeding, without known history of bleeding episode within 3 months of Screening, and without history of bleeding disorder);
    • 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 24-hour Creatinine Clearance or modified Cockcroft-Gault equation (using Ideal Body Mass [IBM] instead of Mass). For subjects that have BMI of > 30 kg/m2 or < 19 kg/m2, 24-hour measured urine creatinine clearance is required;
    • 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 correspondence 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 confirmed by biopsy.
  • Subject has prolymphocytic leukemia.
  • Subject has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to Screening), including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura despite low dose corticosteroids.
  • Subject has previously received ABT-199.
  • Subject has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.
  • Subject has received any of the following within 5 half-lives 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

  Hide Study Locations
Locations
United States, Alabama
Site Reference ID/Investigator# 108135 Withdrawn
Birmingham, Alabama, United States, 35294
United States, Arizona
Site Reference ID/Investigator# 96748 Recruiting
Tucson, Arizona, United States, 85724-5024
Principal Investigator: Site Reference ID/Investigator# 96748         
United States, California
Site Reference ID/Investigator# 112875 Recruiting
Duarte, California, United States, 91010
Principal Investigator: Site Reference ID/Investigator# 112875         
Site Reference ID/Investigator# 91793 Recruiting
La Jolla, California, United States, 92093
Principal Investigator: Site Reference ID/Investigator# 91793         
Site Reference ID/Investigator# 105117 Recruiting
Stanford, California, United States, 94305
Principal Investigator: Site Reference ID/Investigator# 105117         
United States, District of Columbia
Site Reference ID/Investigator# 96954 Recruiting
Washington, District of Columbia, United States, 20007
Principal Investigator: Site Reference ID/Investigator# 96954         
United States, Illinois
Site Reference ID/Investigator# 92499 Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Site Reference ID/Investigator# 92499         
Site Reference ID/Investigator# 96960 Recruiting
Chicago, Illinois, United States, 60637
Principal Investigator: Site Reference ID/Investigator# 96960         
Site Reference ID/Investigator# 92497 Recruiting
Harvey, Illinois, United States, 60426
Principal Investigator: Site Reference ID/Investigator# 92497         
United States, Massachusetts
Site Reference ID/Investigator# 123376 Not yet recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Site Reference ID/Investigator# 123376         
Site Reference ID/Investigator# 92494 Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Site Reference ID/Investigator# 92494         
United States, Michigan
Site Reference ID/Investigator# 102856 Recruiting
Ann Arbor, Michigan, United States, 48109
Principal Investigator: Site Reference ID/Investigator# 102856         
Site Reference ID/Investigator# 97795 Completed
Detroit, Michigan, United States, 48202
United States, New Jersey
Site Reference ID/Investigator# 92500 Recruiting
Hackensack, New Jersey, United States, 07601
Principal Investigator: Site Reference ID/Investigator# 92500         
Site Reference ID/Investigator# 92513 Recruiting
New Brunswick, New Jersey, United States, 08903
Principal Investigator: Site Reference ID/Investigator# 92513         
United States, New York
Site Reference ID/Investigator# 103835 Recruiting
New York, New York, United States, 10032
Principal Investigator: Site Reference ID/Investigator# 103835         
Site Reference ID/Investigator# 94716 Recruiting
New York, New York, United States, 10065
Principal Investigator: Site Reference ID/Investigator# 94716         
Site Reference ID/Investigator# 120875 Withdrawn
Rochester, New York, United States, 14642
United States, North Carolina
Site Reference ID/Investigator# 92498 Withdrawn
Durham, North Carolina, United States, 27710
United States, Ohio
Site Reference ID/Investigator# 92495 Recruiting
Cleveland, Ohio, United States, 44195
Principal Investigator: Site Reference ID/Investigator# 92495         
Site Reference ID/Investigator# 108136 Recruiting
Cleveland, Ohio, United States, 44106
Principal Investigator: Site Reference ID/Investigator# 108136         
United States, Texas
Site Reference ID/Investigator# 92521 Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Site Reference ID/Investigator# 92521         
Australia
Site Reference ID/Investigator# 98837 Recruiting
Brisbane, Australia, 4102
Principal Investigator: Site Reference ID/Investigator# 98837         
Site Reference ID/Investigator# 98835 Recruiting
Coburg, Australia, 3058
Principal Investigator: Site Reference ID/Investigator# 98835         
Site Reference ID/Investigator# 91795 Recruiting
East Melbourne, Australia, 3002
Principal Investigator: Site Reference ID/Investigator# 91795         
Site Reference ID/Investigator# 91794 Recruiting
Parkville, Australia, 3050
Principal Investigator: Site Reference ID/Investigator# 91794         
Site Reference ID/Investigator# 98836 Recruiting
St. Leonards, Australia, 2065
Principal Investigator: Site Reference ID/Investigator# 98836         
Canada
Site Reference ID/Investigator# 99476 Recruiting
Montreal, Canada, H3T 1E2
Principal Investigator: Site Reference ID/Investigator# 99476         
France
Site Reference ID/Investigator# 98840 Recruiting
Bobigny Cedex, France, 93009
Principal Investigator: Site Reference ID/Investigator# 98840         
Site Reference ID/Investigator# 98842 Recruiting
Paris, Cedex 13, France, 75651
Principal Investigator: Site Reference ID/Investigator# 98842         
Site Reference ID/Investigator# 98839 Recruiting
Pierre Benite, France, 69310
Principal Investigator: Site Reference ID/Investigator# 98839         
Site Reference ID/Investigator# 98838 Recruiting
Rouen, France, 76038
Principal Investigator: Site Reference ID/Investigator# 98838         
Germany
Site Reference ID/Investigator# 98847 Recruiting
Cologne, Germany, 50937
Principal Investigator: Site Reference ID/Investigator# 98847         
Site Reference ID/Investigator# 113256 Recruiting
Dresden, Germany, 01307
Principal Investigator: Site Reference ID/Investigator# 113256         
Site Reference ID/Investigator# 113276 Recruiting
Freiburg, Germany, 79106
Principal Investigator: Site Reference ID/Investigator# 113276         
Site Reference ID/Investigator# 113258 Recruiting
Goettingen, Germany, 37075
Principal Investigator: Site Reference ID/Investigator# 113258         
Site Reference ID/Investigator# 121075 Recruiting
Hamburg, Germany, 20099
Principal Investigator: Site Reference ID/Investigator# 121075         
Site Reference ID/Investigator# 98845 Recruiting
Heidelberg, Germany, 69120
Principal Investigator: Site Reference ID/Investigator# 98845         
Site Reference ID/Investigator# 113259 Recruiting
Homburg, Germany, 66421
Principal Investigator: Site Reference ID/Investigator# 113259         
Site Reference ID/Investigator# 113235 Recruiting
Kiel, Germany, 24116
Principal Investigator: Site Reference ID/Investigator# 113235         
Site Reference ID/Investigator# 113236 Recruiting
Mainz, Germany, 55131
Principal Investigator: Site Reference ID/Investigator# 113236         
Site Reference ID/Investigator# 113275 Recruiting
Munich, Germany, 80804
Principal Investigator: Site Reference ID/Investigator# 113275         
Site Reference ID/Investigator# 113237 Recruiting
Munich, Germany, 81377
Principal Investigator: Site Reference ID/Investigator# 113237         
Site Reference ID/Investigator# 92533 Recruiting
Ulm, Germany, 89081
Principal Investigator: Site Reference ID/Investigator# 92533         
Poland
Site Reference ID/Investigator# 98850 Recruiting
Chorzow, Poland, 41-500
Principal Investigator: Site Reference ID/Investigator# 98850         
Site Reference ID/Investigator# 98849 Recruiting
Krakow, Poland, 31-501
Principal Investigator: Site Reference ID/Investigator# 98849         
Site Reference ID/Investigator# 98848 Recruiting
Lublin, Poland, 20-081
Principal Investigator: Site Reference ID/Investigator# 98848         
Site Reference ID/Investigator# 102855 Recruiting
Opole, Poland, 45-061
Principal Investigator: Site Reference ID/Investigator# 102855         
United Kingdom
Site Reference ID/Investigator# 118975 Recruiting
Bournemouth, United Kingdom, BH7 7DW
Principal Investigator: Site Reference ID/Investigator# 118975         
Site Reference ID/Investigator# 119977 Recruiting
Cambridge, United Kingdom, CB2 0QQ
Principal Investigator: Site Reference ID/Investigator# 119977         
Site Reference ID/Investigator# 98863 Recruiting
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Principal Investigator: Site Reference ID/Investigator# 98863         
Site Reference ID/Investigator# 98865 Recruiting
Leicester, United Kingdom, LE1 5WW
Principal Investigator: Site Reference ID/Investigator# 98865         
Site Reference ID/Investigator# 98860 Recruiting
Liverpool, United Kingdom, L7 8XP
Principal Investigator: Site Reference ID/Investigator# 98860         
Site Reference ID/Investigator# 98862 Recruiting
London, United Kingdom, EC1A 7BE
Principal Investigator: Site Reference ID/Investigator# 98862         
Site Reference ID/Investigator# 119975 Recruiting
London, United Kingdom, SE5 9RS
Principal Investigator: Site Reference ID/Investigator# 119975         
Site Reference ID/Investigator# 98864 Recruiting
Manchester, United Kingdom, M20 4BX
Principal Investigator: Site Reference ID/Investigator# 98864         
Site Reference ID/Investigator# 119976 Recruiting
Oxford, United Kingdom, OX3 7LE
Principal Investigator: Site Reference ID/Investigator# 119976         
Site Reference ID/Investigator# 118335 Recruiting
Plymouth, Devon, United Kingdom, PL6 8DH
Principal Investigator: Site Reference ID/Investigator# 118335         
Site Reference ID/Investigator# 98861 Recruiting
Sutton, United Kingdom, SM2 5PT
Principal Investigator: Site Reference ID/Investigator# 98861         
Site Reference ID/Investigator# 123199 Recruiting
Sutton, United Kingdom, SM2 5PT
Principal Investigator: Site Reference ID/Investigator# 123199         
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: October 28, 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 29, 2014