Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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, Inc.
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01682616
First received: June 26, 2012
Last updated: November 11, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia
Drug: ABT-199
Drug: Rituximab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.


Estimated Enrollment: 50
Study Start Date: August 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
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.

  Eligibility

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

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.
  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: NCT01682616

Locations
United States, California
Site Reference ID/Investigator# 70398
La Jolla, California, United States, 92037
United States, Illinois
Site Reference ID/Investigator# 71593
Chicago, Illinois, United States, 60611
United States, New York
Site Reference ID/Investigator# 71813
New Hyde Park, New York, United States, 11042
United States, North Carolina
Site Reference ID/Investigator# 123418
Durham, North Carolina, United States, 27710
Site Reference ID/Investigator# 71393
Durham, North Carolina, United States, 27710
Australia
Site Reference ID/Investigator# 70394
East Melbourne, Australia, 3002
Site Reference ID/Investigator# 70393
Parkville, Australia, 3050
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Genentech, Inc.
Investigators
Study Director: Elisa Cerri, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01682616     History of Changes
Other Study ID Numbers: M13-365
Study First Received: June 26, 2012
Last Updated: November 11, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration

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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014