A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma

This study is currently recruiting participants.
Verified January 2014 by AbbVie
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01328626
First received: April 1, 2011
Last updated: January 28, 2014
Last verified: January 2014

April 1, 2011
January 28, 2014
June 2011
July 2014   (final data collection date for primary outcome measure)
  • Determination of dose limiting toxicity (DLT), maximum tolerated dose (MTD), recommended phase two dose (RPTD), and lead-in period regimen [ Time Frame: Lead-in period (2-5 weeks) plus 3 weeks of study drug administration at the designated cohort dose (continuous dosing) ] [ Designated as safety issue: Yes ]
    Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, underlying illness, concurrent illness, or concomitant medication, will be considered a DLT. Dose limiting toxicities of tumor lysis syndrome observed during the lead-in period will be attributed to the lead-in period.
  • Determination of plasma peak concentration (Cmax), trough concentration (Ctrough), area under the concentration versus time curve (AUC) and urine recovery of ABT-199 [ Time Frame: Up to Week 24 for ABT-199 ] [ Designated as safety issue: No ]
    Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points
  • Safety assessment [ Time Frame: First 16 weeks of study drug administration and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months) ] [ Designated as safety issue: Yes ]
    Adverse event monitoring, vital signs, physical examination, and laboratory assessments
  • Determination of dose limiting toxicity (DLT) and maximum tolerated dose (MTD) [ Time Frame: First 3 weeks of study drug administration (continuous dosing) ] [ Designated as safety issue: Yes ]
    Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, intercurrent illness, or concomitant medication, will be considered a DLT
  • Pharmacokinetic profile evaluation [ Time Frame: First 3 weeks of study drug administration and at Weeks 6, 12, 16 and 24 (continuous dosing) ] [ Designated as safety issue: No ]
    Blood and urine samples for pharmocokinetic analysis of ABT-199 will be collected at designated time points
Complete list of historical versions of study NCT01328626 on ClinicalTrials.gov Archive Site
  • Preliminary efficacy assessment [ Time Frame: Starting Week 4 for clinical disease progression and Week 6 for tumor response; and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months) ] [ Designated as safety issue: No ]
    Tumor response or clinical disease progression
  • Food Effect [ Time Frame: Week 1 Day -7 (single dose), Week 1 Day 1, and Week 6 Day 1 ] [ Designated as safety issue: No ]
    Effect of food on ABT-199 pharmacokinetic profile (Cohorts 1-6 in Arm B subjects only)
  • Biomarkers and pharmacogenetics [ Time Frame: Screening, Week 1 Day 1, Week 6 Day 1, Week 24 Day 1, time of relapse and Final visit. Timepoints vary by disease type, assay performed and whether dose escalation or expanded safety portion of the study. ] [ Designated as safety issue: No ]
    Various biomarkers are being collected to determine if they can be used to measure the status of a disease and/or the effects of treatments.
  • Minimal residual disease collection (MRD) [ Time Frame: At least 2 months after the CR, CRi criteria for tumor response are first met. Every 12 weeks thereafter, until MRD negativity has been achieved (in peripheral blood). ] [ Designated as safety issue: No ]
    MRD assessed in the peripheral blood and/or bone marrow (BM) either by four color flow cytometry or ASO-PCR, will be measured in CLL subjects achieving CR/CRi.
  • Preliminary efficacy assessment [ Time Frame: First 3 weeks of study drug administrations and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months) ] [ Designated as safety issue: No ]
    Tumor response or clinical disease progression
  • Safety assessment [ Time Frame: First 3 weeks of study drug administrations and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months) ] [ Designated as safety issue: Yes ]
    Adverse event monitoring, vital signs, physical examination, lymphocyte enumeration, 12-lead ECG, 2D echocardiogram/multiple gaited acquisition scan (MUGA), and laboratory assessments
Not Provided
Not Provided
 
A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma
A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma

This is a Phase 1, open-label, multicenter study evaluating the safety and PK profile of ABT-199 under a once daily dosing schedule. Two arms will be implemented for dose escalation: Arm A, CLL/SLL subjects and Arm B, NHL subjects. Arm A is designed to enroll approximately 116 subjects with relapsed or refractory CLL or SLL and Arm B is designed to enroll approximately 95 subjects with relapsed or refractory NHL. Fifty-six subjects were enrolled in Arm A and approximately 55 subjects will be enrolled in Arm B during the dose escalation portion of the study, with the objective of defining dose limiting toxicities (DLTs) and the MTD. Once the MTD is declared for the arm, approximately 60 additional CLL/SLL subjects in Arm A and approximately 20 additional DLBCL subjects and 20 additional follicular lymphoma subjects in Arm B will be enrolled in an expanded safety portion of the study at the recommended phase 2 dose (RPTD) and schedule.

Interventional Study Design - Primary Purpose: Determination of safety and tolerability.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Chronic Lymphocytic Leukemia
  • Non-Hodgkin Lymphoma
Drug: ABT-199
Arm A (Cohorts 1-8) and Arm B (Cohort 1-6): Subjects in dose escalation phase will receive 1 dose of ABT-199, followed by 6 days off drug, followed by continuous once daily dosing with ABT-199. Arm B (Cohorts 7+): Subjects in dose escalation phase will receive continuous once daily dosing with ABT-199. Arm A and Arm B: Subjects in expanded safety cohort will receive continuous once daily dosing with ABT-199.
Other Name: ABT-199
  • Experimental: Arm A (CLL/SLL subjects)
    Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) subjects
    Intervention: Drug: ABT-199
  • Experimental: Arm B (NHL subjects)
    Non-Hodgkin lymphoma (NHL) subjects
    Intervention: Drug: ABT-199
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
211
July 2014
July 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subject must have either:

    • (Arm A) relapsed or refractory CLL/SLL and require treatment in the opinion of the Investigator. Subject must have relapsed following or be refractory to standard treatments such as fludarabine based regimens (F, FC, FR, FCR) or alkylator (chlorambucil, bendamustine) based regimens. In addition, there are no other curative options, and the subject has exhausted options that would be considered standard of care, or
    • (Arm B) relapsed or refractory NHL and require treatment in the opinion of the Investigator. Subject must have histologically documented diagnosis of NHL as defined in the World Health Organization classification scheme, except as noted in the exclusion criteria. Subject must have relapsed following or be refractory to standard treatments such as R-CHOP, R-CVP, or fludarabine based regimens. In addition, there are no other curative options, and the subject has exhausted options that would be considered standard of care. Subjects with other lymphoproliferative diseases can be considered in consultation with the Abbott medical monitor.
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 1.
  • Subject must have adequate bone marrow independent of growth factor support per local laboratory reference range at Screening.
  • Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening.

Exclusion Criteria:

  • CLL subject has undergone an allogeneic or autologous stem cell transplant or NHL subject has undergone an allogeneic stem cell transplant or has been diagnosed with Post-Transplant Lymphoproliferative Disease, Burkitt's lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia.
  • Subject has tested positive for HIV.
  • Subject has a cardiovascular disability status of New York Heart Association Class greater or equal to 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity, results in fatigue, palpitations, dyspnea or anginal pain.
  • Subject has a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the Investigator would adversely affect his/her participating in this study.
  • Subject has received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug.
Both
18 Years and older
No
Contact: Niki Rudersdorf, BS 847-937-2497 niki.rudersdorf@abbvie.com
Contact: Michael Dawson 847-938-9467 michael.dawson@abbvie.com
United States,   Australia
 
NCT01328626
M12-175
No
AbbVie ( AbbVie (prior sponsor, Abbott) )
AbbVie (prior sponsor, Abbott)
Genentech
Study Director: Sari Enschede, MD AbbVie
AbbVie
January 2014

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