A Phase 1b Study Evaluating the Safety and Tolerability of ABT-199 in Combination With Rituximab in Subjects With Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01682616
First received: June 26, 2012
Last updated: June 25, 2014
Last verified: June 2014

June 26, 2012
June 25, 2014
August 2012
May 2015   (final data collection date for primary outcome measure)
Assess the safety profile, to determine the maximum tolerated dose and Recommended Phase Two Dose of ABT-199 when administered in combination with rituximab (R) in subjects with relapsed chronic lymphocytic leukemia and small lymphocytic lymphoma. [ Time Frame: Continuous dosing with study drug at the designated cohort dose level up to Month 6. At the end of combination treatment, ABT-199 monotherapy may continue for up to 2 years following the date of the last subject enrolled. ] [ Designated as safety issue: Yes ]
Protocol-defined events, which are attributed as having a reasonable possibility of being related to the administration of ABT-199 and/or rituximab, or can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, concurrent illness, underlying disease or concomitant medication, will be considered a dose limiting toxicity.
Assess the safety of ABT-199 when administered in combination with rituximab (R) in subjects with relapsed chronic lymphocytic leukemia. [ Time Frame: Continuous dosing with study drug at the designated cohort dose level up to Week 30. ] [ 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, concurrent illness, or concomitant medication, will be considered a dose limiting toxicity.
Complete list of historical versions of study NCT01682616 on ClinicalTrials.gov Archive Site
  • Assess the exploratory efficacy of the combination ABT-199 and rituximab. [ Time Frame: Tumor Assessments will be performed at: Screening, Month 1 Day 1, Month 3 Day 1 and Month 7 Day 1 , every 12 weeks thereafter, and at least 2 months after Partial Remission, Complete Remission or Complete Remission with incomplete bone marrow recovery ] [ Designated as safety issue: No ]
    Tumor response or clinical disease progression
  • Determination of peak concentration (Cmax), trough concentration (Ctrough) and/or area under the concentration versus time curve (AUC) of ABT-199 and/or Rituximab. [ Time Frame: Up to Month 6 for ABT-199 and Rituximab. ] [ Designated as safety issue: No ]
    Blood samples for analysis of ABT-199 and rituximab will be collected at designated time points.
  • Assess the exploratory efficacy and the pharmacokinetic profile of the combination ABT-199 and rituximab. [ Time Frame: Tumor Assessments will be performed at following timepoints: Screening, Week 30, Week4Day1, Week14 Day 1 and Week 38 Day1, and at least 2 months after Complete Remission or Complete Remission with incomplete bone marrow recovery is first met, ] [ Designated as safety issue: No ]

    Tumor response or clinical disease progression

    Time Frame (continued): and at the Final Visit.

  • Determination of peak concentration (Cmax), trough concentration (Ctrough) and/or area under the concentration versus time curve (AUC) of ABT-199 and/or Rituximab [ Time Frame: Up to Week 26 for ABT-199 and Rituximab ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetic analysis of ABT-199 and rituximab will be collected at designated time points.
Assess the exploratory pharmacodynamics and pharmacogenetics of the combination of ABT-199 and rituximab. [ Time Frame: MRD Assessments will be performed at following timepoints: At least 2 months after CR/CRi criteria for tumor response first met, every 12 weeks thereafter until MRD negativity is achieved, and as needed. ] [ Designated as safety issue: Yes ]
Minimal residual disease (MRD) will be assessed in the peripheral blood and bone marrow (BM) either by flow cytometry or real-time PCR.
Not Provided
 
A Phase 1b Study Evaluating the Safety and Tolerability of ABT-199 in Combination With Rituximab in Subjects With Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
A Phase 1b Study Evaluating the Safety and Tolerability of ABT-199 in Combination With Rituximab in Subjects With Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

This is a Phase 1b, open-label, multicenter study evaluating the safety and tolerability of ABT-199 in combination with rituximab in up to 50 subjects with Relapsed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. The primary objectives of this study are to assess the safety profile, to determine the maximum tolerated dose and establish the Recommended Phase Two Dose of ABT-199 when administered in combination with rituximab. The dose escalation portion of the study will include approximately 30 subjects. Once the recommended phase two dose and schedule have been determined, up to 20 additional subjects will be enrolled in an expanded safety portion of the study.

Not Provided
Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Small Lymphocytic Lymphoma
  • Chronic Lymphocytic Leukemia
  • Drug: ABT-199
    ABT-199 is taken continuously once daily. This is a dose escalation study, therefore the dose of ABT-199 will change throughout the study.
  • Drug: Rituximab
    Rituximab will be given by intravenous infusion on day 1 of Months 1, 2, 3, 4, 5, and 6.
Experimental: Arm 1
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Interventions:
  • Drug: ABT-199
  • Drug: Rituximab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
50
February 2016
May 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subject must be greater then or equal to 18 years of age.
  • Subject must have relapsed Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma.
  • Subject has an Eastern Cooperative Oncology Group performance score of 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:

  • Chronic lymphocytic leukemia or Small Lymphocytic Lymphoma subject has undergone an allogeneic or autologous stem cell transplant.
  • Subject has uncontrolled autoimmune hemolytic anemia or thrombocytopenia.
  • Subject has tested positive for human immunodeficiency virus.
  • Seropositivity for hepatitis B surface antigen or hepatitis C virus antibody or ribonucleic acid.
  • History of severe allergic or anaphylactic reactions to rituximab.
  • Subject has received a live viral vaccine within 6 months prior to the first dose of study drug.
  • Subject has received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug.
  • Subject has received any of the following within 14 days prior to the first dose of study drug, or has not recovered to less than grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:

    • Any anti-cancer therapy including chemotherapy, immunotherapy, or radiotherapy;
    • Investigational therapy, including targeted small molecule agents.
  • Subject has a cardiovascular disability status of New York Heart Association Class greater then or equal to 2. Class 2 is defined as cardiac disease in which subjects 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 a history of other active malignancies other than CLL/SLL within the past 2 years prior to study entry, with the exception of:

    • Adequately treated in situ carcinoma of the cervix uteri;
    • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
    • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  • Subject has malabsorption syndrome or other condition that precludes enteral route of administration.
  • Subject has a history of a prior significant toxicity, other than thrombocytopenia or neutropenia from another Bcl-2 family protein inhibitor.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia
 
NCT01682616
M13-365
No
AbbVie ( AbbVie (prior sponsor, Abbott) )
AbbVie (prior sponsor, Abbott)
Genentech
Study Director: Elisa Cerri, MD AbbVie
AbbVie
June 2014

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