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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie
ClinicalTrials.gov Identifier:
NCT01889186
First received: June 26, 2013
Last updated: April 21, 2017
Last verified: April 2017
June 26, 2013
April 21, 2017
June 27, 2013
May 12, 2020   (Final data collection date for primary outcome measure)
  • 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. ]
    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 the study. ]
    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 2 years after the last subject has enrolled in the study. ]
    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 2 years after the last subject has enrolled in the study. ]
    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 has enrolled in the study. ]
    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 the study. ]
    Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study.
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. ]
To evaluate the efficacy of ABT-199 monotherapy in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion.
Complete list of historical versions of study NCT01889186 on ClinicalTrials.gov Archive Site
  • Complete Remission (CR) rate [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    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. ]
    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. ]
    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. ]
    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 ]
    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. ]
    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. ]
    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. ]
    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 2 years after the last subject has enrolled in the study. ]
    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 2 years after the last subject has enrolled in the study. ]
    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. ]
    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. ]
    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 the study. ]
    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)
  • Event free survival [ Time Frame: Measured up to 5 years after the last subject has enrolled in the study. ]
    Event-free survival is defined as the number of days from the date of first dose to the date of earliest disease progression, death, or start of a new anti-leukemic therapy.
  • Time to first response [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Time to first response will be defined as the number of days from the date of first dose to the date of the first sign of response (CR, CRi, nPR, or PR) given the subject has had a CR, CRi, confirmed nPR or confirmed PR per the 2008 Modified IWCLL NCI-WG criteria.
  • Time to 50% reduction in absolute lymphocyte count [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    Time to 50% reduction in absolute lymphocyte count will be defined as the number of days (hours if applicable) from the date of first dose to the date when the absolute lymphocyte count has reduced to 50% of the baseline value.
  • Complete Remission (CR) rate [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
    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. ]
    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. ]
    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. ]
    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 ]
    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. ]
    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. ]
    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. ]
    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. ]
    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. ]
    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. ]
    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. ]
    Subjects will be monitored for clinical and laboratory evidence of adverse events throughout the study.
Not Provided
Not Provided
 
A Study of the Efficacy of ABT-199 in Subjects With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia With the 17p Deletion
A Phase 2 Open-Label Study of the Efficacy of ABT-199 (GDC-0199) in Subjects With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia Harboring the 17p Deletion
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 closed.
Not Provided
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
  • Chronic Lymphocytic Leukemia
  • 17 p Deletion
  • Cancer of the Blood and Bone Marrow
Drug: ABT-199
Tablet
Experimental: Single arm
Single arm
Intervention: Drug: ABT-199
Stilgenbauer S, Eichhorst B, Schetelig J, Coutre S, Seymour JF, Munir T, Puvvada SD, Wendtner CM, Roberts AW, Jurczak W, Mulligan SP, Böttcher S, Mobasher M, Zhu M, Desai M, Chyla B, Verdugo M, Enschede SH, Cerri E, Humerickhouse R, Gordon G, Hallek M, Wierda WG. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016 Jun;17(6):768-78. doi: 10.1016/S1470-2045(16)30019-5. Epub 2016 May 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
150
May 12, 2020
May 12, 2020   (Final data collection date for primary outcome measure)

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 organomegaly 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) or previously untreated CLL (previously untreated CLL subjects must have received no prior chemotherapy or immunotherapy. Subjects with a history of emergency, loco-regional radiotherapy (e.g., for relief of compressive signs or symptoms) are eligible. In addition, subjects must meet the CLL diagnostic criteria above and must have > 5 × 109/L B Lymphocytes in the peripheral blood.);
    • 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 14 days or 5 half-lives as applicable 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.
Sexes Eligible for Study: All
18 Years to 99 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Canada,   France,   Germany,   Poland,   United Kingdom,   United States
 
 
NCT01889186
M13-982
2012-004027-20 ( EudraCT Number )
Yes
Not Provided
Not Provided
Not Provided
AbbVie
AbbVie
Genentech, Inc.
Study Director: Su Kim, MD AbbVie
AbbVie
April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP