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

Safety Study of ABT-263 in Combination With Rituximab in Lymphoid Cancers

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:
NCT00788684
First received: November 10, 2008
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

This is a Phase 1 study evaluating the safety of ABT-263 administered in combination with rituximab in subjects with CD20-positive lymphoproliferative disorders.


Condition Intervention Phase
CD20-Positive Lymphoid Malignancies
Chronic Lymphoid Leukemia
Hematological Malignancies
Non-Hodgkin's Lymphoma
Drug: ABT-263
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 1 Study Evaluating the Safety of ABT-263 in Combination With Rituximab in Subjects With CD20-positive Lymphoid Malignancies

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Assess the safety profile and characterize the pharmacokinetics of ABT-263 when administered in combination with rituximab [ Time Frame: Safety and pharmacokinetics will be assessed until the subject discontinues the study or transitions to the extension portion of the study (whichever comes first). ] [ Designated as safety issue: No ]
  • Determination of dose limiting toxicity (DLT) and maximum tolerated dose (MTD) when ABT-263 is administered in combination with rituximab [ Time Frame: DLTs and MTD will be assessed after all subjects in a dose level have completed the lead-in period plus 28 days if dosing with ABT-263 and rituximab ] [ Designated as safety issue: No ]
  • Extension Study: Continued assessment of the safety profile of ABT-263 when administered in combination with rituximab [ Time Frame: Safety will be assessed until the subject discontinues the extension portion of the study. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Preliminary progression-free survival (PFS), response rate, duration of response and overall survival (OS) [ Time Frame: PFS will be measured upon study completion via statistical analysis of the study data. ] [ Designated as safety issue: No ]
  • Extension Study: Continued assessment of the preliminary progression-free survival (PFS), response rate, duration of response and overall survival (OS) [ Time Frame: PFS will be measured upon study completion via statistical analysis of the study data. ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: July 2009
Estimated Study Completion Date: September 2016
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ABT-263 + rituximab Drug: ABT-263
ABT-263: oral solution or tablets, once daily dosing until disease progression
Other Name: navitoclax
Drug: rituximab
IV infusion once weekly for four doses
Other Name: Rituxan

  Eligibility

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

Inclusion Criteria:

  • Diagnosed with a CD20-positive lymphoproliferative disorder (REAL/WHO) and bi-dimensionally measurable disease with at least 1 lesion > or = 1.0 cm
  • ECOG performance score of <or = 1
  • Adequate bone marrow function, independent of growth factor support (with the exception of subjects with bone marrow that is heavily infiltrated with underlying disease [80% or more] who may use growth factor to achieve ANC eligibility criteria) per local laboratory reference range as follows: Absolute Neutrophil count (ANC) ≥ 1000/μL; Platelets ≥ 100,000/mm3 (untransfused); Hemoglobin ≥ 9.0 g/dL.
  • Subjects who have a history of autologous stem cell transplant (e.g., bone marrow) must be > 6 months post transplant and have adequate bone marrow function, independent of any growth stimulating factors (with the exception of subjects with bone marrow that is heavily infiltrated with underlying disease [80% or more] who may use growth factor to achieve ANC eligibility criteria) per local laboratory reference range as follows: Absolute Neutrophil count (ANC) ≥ 1500/μL; Platelets ≥ 125,000/mm3 (untransfused); Hemoglobin ≥ 10.0 g/dL.
  • Subject must have adequate renal, hepatic and coagulation function per local laboratory reference range as follows: Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 50 mL/min; AST and ALT ≤ 3.0 × the upper normal limit (ULN); Bilirubin ≤ 1.5 × ULN. Subjects with Gilbert's Syndrome may have a Bilirubin > 1.5 × ULN; aPTT, PT not to exceed 1.2 × ULN
  • Females must be surgically sterile, postmenopausal (at least 1 year), or have negative pregnancy test at screening on serum sample and prior to first dose of study drug on urine sample. Females not surgically sterile or postmenopausal (at least 1 year) and non-vasectomized males must practice at least 1 of the following:total abstinence from sexual intercourse (min.1 complete menstrual cycle),a vasectomized partner, hormonal contraceptives for at least 3 months prior to study drug administration, or double-barrier method.
  • Inclusion Criteria (Extension Study) Subjects who enter the Extension Study must continue to meet all Inclusion and Exclusion criteria, with the exception of inclusion criteria regarding measurable disease and inclusion criteria regarding laboratory parameters. Subjects entering the Extension Study must also have stable lab values per local laboratory reference ranges. In addition they must meet the following lab criteria:
  • Subjects must meet the following hematology and coagulation lab criteria:

    • Platelet counts must be ≥ 25,000/mm3 (untransfused). Platelet counts ≤ 50,000/mm3 must be stable and monitored at an increased frequency at the discretion of the investigator.
    • Absolute Neutrophil count (ANC) ≥ 500/μL. ANC ≥ 500/μL and < 1,000/μL should be monitored at an increased frequency at the discretion of the investigator.
    • Hemoglobin of ≥ 8.0 g/dL.
    • aPTT, PT is not to exceed 1.2 × ULN.
  • Subjects' chemistry values must not exceed Grade 2. Grade 2 chemistry labs should be monitored at an increased frequency at the discretion of the investigator. Subjects must meet the following chemistry criteria:

    • Serum creatinine ≤ 3.0 × the upper normal limit (ULN) of institution's normal range.
    • AST and ALT ≤ 5.0 × the upper normal limit (ULN) of institution's normal range.
    • Bilirubin ≤ 3 × ULN. Subjects with Gilbert's Syndrome may be allowed to have a Bilirubin > 3 × ULN based on a joint decision between the investigator and Abbott medical monitor.

Exclusion Criteria:

  • History of or clinically suspicious for cancer-related Central Nervous System (CNS) disease, allogeneic stem cell transplant, recurrent significant infections, previous or current malignancies within the last 5 years ( except: adequately treated in situ carcinoma of the cervix uteri; basal or squamous cell carcinoma of the skin; in situ carcinoma of the bladder; previous malignancy confined and surgically resected with curative intent), toxicity from rituximab that resulted in permanent discontinuation of treatment or toxicity from ABT-263 or another Bcl-2 family protein inhibitor, significant cardiovascular disease (e.g., MI within 6 months), renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic or hepatic disease that would adversely affect participation, severe (defined as Grade 4 and/or requiring permanent discontinuation of prior antibody therapy) allergic or anaphylactic reactions to human, humanized, chimeric or murine monoclonal antibodies
  • The subject has an underlying, predisposing condition of bleeding or currently exhibits signs of clinically significant bleeding. The subject has a recent history of non-chemotherapy induced thrombocytopenic associated bleeding within six months prior to the first dose of study drug. The subject has active peptic ulcer disease or other hemorrhagic esophagitis/gastritis or active immune thrombocytopenic purpura (ITP) or a history of being refractory to platelet transfusions (within six months prior to the first dose of study drug).
  • Female subject is pregnant or breast-feeding
  • Subject has tested positive for HIV, Hepatitis B or Hepatitis C infection, (Subjects who test positive for anti-HBc (carrier) will be allowed to enroll)
  • Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: active systemic fungal infection; diagnosis of fever and neutropenia within one week prior to study drug administration
  • Received steroid therapy for anti-neoplastic intent within seven days prior to the first dose of study drug,received aspirin within seven days prior to the first dose of study drug, CYP3A inhibitors (e.g., ketoconazole, clarithromycin) within 7 days prior to the administration of the first dose of study drug, radio-immunotherapy within six months prior to first dose of study drug,received any anti-cancer therapy within fourteen days 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: NCT00788684

Locations
United States, Arizona
Site Reference ID/Investigator# 16721
Tucson, Arizona, United States, 85724-5024
United States, California
Site Reference ID/Investigator# 9782
Stanford, California, United States, 94305
United States, Ohio
Site Reference ID/Investigator# 9784
Cleveland, Ohio, United States, 44195
United States, Wisconsin
Site Reference ID/Investigator# 21701
Madison, Wisconsin, United States, 53792-5156
Australia
Site Reference ID/Investigator# 25067
East Melbourne, Australia, 3002
Site Reference ID/Investigator# 9781
Parkville, Australia, 3050
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: NCT00788684     History of Changes
Other Study ID Numbers: M10-166
Study First Received: November 10, 2008
Last Updated: August 18, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
United States: Food and Drug Administration

Keywords provided by AbbVie:
CD20-Positive Lymphoid Malignancies
Rituximab
Chronic Lymphoid Leukemia
ABT-263
Hematological Malignancies
Non-Hodgkin's Lymphoma
Navitoclax

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

ClinicalTrials.gov processed this record on November 27, 2014