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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. (see Contacts and Locations)
Verified November 2014 by AbbVie
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01328626
First received: April 1, 2011
Last updated: November 11, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Non-Hodgkin Lymphoma
Drug: ABT-199
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 211
Study Start Date: June 2011
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (CLL/SLL subjects)
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) subjects
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 B (NHL subjects)
Non-Hodgkin lymphoma (NHL) subjects
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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01328626

Contacts
Contact: Lori A Gressick, BS 847-936-1579 lori.gressick@abbvie.com
Contact: Michael Dawson 847-938-9467 michael.dawson@abbvie.com

Locations
United States, Arizona
Site Reference ID/Investigator# 52902 Recruiting
Tucson, Arizona, United States, 85724-5024
Principal Investigator: Site Reference ID/Investigator# 52902         
United States, California
Site Reference ID/Investigator# 48325 Recruiting
La Jolla, California, United States, 92093
Principal Investigator: Site Reference ID/Investigator# 48325         
United States, Massachusetts
Site Reference ID/Investigator# 48324 Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Site Reference ID/Investigator# 48324         
United States, New York
Site Reference ID/Investigator# 56810 Recruiting
New York, New York, United States, 10065
Principal Investigator: Site Reference ID/Investigator# 56810         
United States, Texas
Site Reference ID/Investigator# 48326 Recruiting
Houston, Texas, United States, 77030-4009
Principal Investigator: Site Reference ID/Investigator# 48326         
United States, Washington
Site Reference ID/Investigator# 52882 Recruiting
Seattle, Washington, United States, 98109
Principal Investigator: Site Reference ID/Investigator# 52882         
United States, Wisconsin
Site Reference ID/Investigator# 56811 Recruiting
Madison, Wisconsin, United States, 53705-2275
Principal Investigator: Site Reference ID/Investigator# 56811         
Australia
Site Reference ID/Investigator# 48323 Recruiting
East Melbourne, Australia, 3002
Principal Investigator: Site Reference ID/Investigator# 48323         
Site Reference ID/Investigator# 48322 Recruiting
Parkville, Australia, 3050
Principal Investigator: Site Reference ID/Investigator# 48322         
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Genentech, Inc.
Investigators
Study Director: Sari Enschede, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01328626     History of Changes
Other Study ID Numbers: M12-175
Study First Received: April 1, 2011
Last Updated: November 11, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
United States: Food and Drug Administration

Keywords provided by AbbVie:
Safety
Maximum Tolerated Dose
ABT-199
Cancer
Pharmacokinetics
Non-Hodgkin Lymphoma
Preliminary Efficacy
Chronic Lymphocytic Leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 24, 2014