Overview

This trial is active, not recruiting.

Conditions chronic lymphocytic leukemia, 17 p deletion, cancer of the blood and bone marrow
Treatment abt-199
Phase phase 2
Target BCL-2
Sponsor AbbVie
Collaborator Genentech, Inc.
Start date June 2013
End date December 2016
Trial size 150 participants
Trial identifier NCT01889186, 2012-004027-20, M13-982

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Single arm
abt-199
Tablet

Primary Outcomes

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.
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.
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 has enrolled in the study.
Change in clinical laboratory test results (Expanded Safety Cohort)
time frame: Measured from Day -1 up to 5 years after the last subject has enrolled in the study.
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.
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.

Secondary Outcomes

Measure
Complete Remission (CR) rate
time frame: Measured up to 2 years after the last subject has enrolled in the study.
Partial Remission (PR) rate
time frame: Measured up to 2 years after the last subject has enrolled in the study.
Duration of response
time frame: Measured up to 2 years after the last subject has enrolled in the study.
Progression-free survival
time frame: Measured up to 5 years after the last subject has enrolled in the study.
Time to progression
time frame: Measured up to 5 years after the last subject has enrolled in the study
Overall survival
time frame: Measured up to 5 years after the last subject has enrolled in the study.
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.
Number of subjects with adverse events (Main Cohort)
time frame: Measured up to 5 years after the last subject has enrolled in the study.
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.
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.
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.
Percentage of subjects with adverse events (Main Cohort)
time frame: Measured up to 5 years after the last subject has enrolled in the study.
Overall Response Rate (ORR) (Expanded Safety Cohort)
time frame: Measured up to 2 years after the last subject has enrolled on the study.
Event free survival
time frame: Measured up to 5 years after the last subject has enrolled in the study.
Time to first response
time frame: Measured up to 5 years after the last subject has enrolled in the study.
Time to 50% reduction in absolute lymphocyte count
time frame: Measured up to 5 years after the last subject has enrolled in the study.

Eligibility Criteria

Male or female participants from 18 years up to 99 years old.

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.

Additional Information

Official title 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
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by AbbVie.