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Trial record 3 of 3 for:    12-175

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01328626
Recruitment Status : Active, not recruiting
First Posted : April 5, 2011
Last Update Posted : November 13, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE April 1, 2011
First Posted Date  ICMJE April 5, 2011
Last Update Posted Date November 13, 2019
Actual Study Start Date  ICMJE June 14, 2011
Estimated Primary Completion Date May 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2018)
  • 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) ]
    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.
  • Number of subjects with adverse events [ Time Frame: First 16 weeks of study drug administration and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months) ]
  • Determination of plasma peak concentration (Cmax) of ABT-199 [ Time Frame: Up to Week 24 for ABT-199 ]
    Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points
  • Determination of trough concentration (Ctrough) of ABT-199 [ Time Frame: Up to Week 24 for ABT-199 ]
    Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points
  • Determination of area under the concentration versus time curve (AUC) of ABT-199 [ Time Frame: Up to Week 24 for ABT-199 ]
    Blood and urine samples for pharmacokinetic analysis of ABT-199 will be collected at designated time points
Original Primary Outcome Measures  ICMJE
 (submitted: April 1, 2011)
  • Determination of dose limiting toxicity (DLT) and maximum tolerated dose (MTD) [ Time Frame: First 3 weeks of study drug administration (continuous dosing) ]
    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) ]
    Blood and urine samples for pharmocokinetic analysis of ABT-199 will be collected at designated time points
Change History Complete list of historical versions of study NCT01328626 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2018)
  • Food Effect - Cmax [ Time Frame: Approximately 3 days ]
    Pharmacokinetic (PK) parameter Cmax (maximum plasma concentration of ABT-199) between each diet (ABT-199 under fasting versus low-fat, and fasting versus high-fat conditions (Cohorts 1-6 in Arm B subjects only)
  • 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) ]
    Tumor response or clinical disease progression
  • 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). ]
    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.
  • Food Effect - Tmax [ Time Frame: Approximately 3 days ]
    Pharmacokinetic (PK) parameter Tmax (time to reach maximum plasma concentration of ABT-199) between each diet (ABT-199 under fasting versus low-fat, and fasting versus high-fat conditions (Cohorts 1-6 in Arm B subjects only)
  • Food Effect - AUC [ Time Frame: Approximately 3 days ]
    Pharmacokinetic (PK) parameter AUC (area under the concentration-time curve from time zero to hour 24 of ABT-199) between each diet (ABT-199 under fasting versus low-fat, and fasting versus high-fat conditions (Cohorts 1-6 in Arm B subjects only)
Original Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2011)
  • Preliminary efficacy assessment [ Time Frame: First 3 weeks of study drug administration and every 4 weeks thereafter (continuous dosing for an anticipated maximum duration of 9 months) ]
    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) ]
    Adverse event monitoring, vital signs, physical examination, lymphocyte enumeration, 12-lead ECG, 2D echocardiogram/multiple gaited acquisition scan (MUGA), and laboratory assessments
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Interventional Study Design - Primary Purpose: Determination of safety and tolerability.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia
  • Non-Hodgkin Lymphoma
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 1, 2018)
222
Original Estimated Enrollment  ICMJE
 (submitted: April 1, 2011)
36
Estimated Study Completion Date  ICMJE May 15, 2020
Estimated Primary Completion Date May 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01328626
Other Study ID Numbers  ICMJE M12-175
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Genentech, Inc.
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date November 2019

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