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

NCT00788684 | Completed Phase 1 FDA Drug

• 1 other identifier: M10-166
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a Phase 1 study evaluating the safety of ABT-263 administered in combination with rituximab in participants with CD20-positive lymphoproliferative disorders. The extension portion of the study will allow active participants to continue to receive ABT-263 for up to 14 years after the last participant transitions with quarterly study evaluations.

Conditions

CD20-Positive Lymphoid Malignancies; Chronic Lymphoid Leukemia; Hematological Malignancies; Non-Hodgkin's Lymphoma

Keywords

Non-Hodgkin's Lymphoma; Rituximab; Chronic Lymphoid Leukemia; Hematological Malignancies; ABT-263; Navitoclax; CD20-Positive Lymphoid Malignancies

Outcome Measures

Primary Outcomes (3)

• Extension Study: Continued assessment of the safety profile of ABT-263 when administered in combination with rituximab

  Safety will be assessed until the participant discontinues the extension portion of the study.

• Assess the safety profile and characterize the pharmacokinetics of ABT-263 when administered in combination with rituximab

  Safety and pharmacokinetics will be assessed until the participant discontinues the study or transitions to the extension portion of the study (whichever comes first).

• Determination of dose limiting toxicity (DLT) and maximum tolerated dose (MTD) when ABT-263 is administered in combination with rituximab

  DLTs and MTD will be assessed after all participants in a dose level have completed the lead-in period plus 28 days if dosing with ABT-263 and rituximab

Secondary Outcomes (2)

• Extension Study: Continued assessment of the preliminary progression-free survival (PFS), response rate, and duration of response.

  PFS will be measured upon study completion via statistical analysis of the study data.

• Preliminary progression-free survival (PFS), response rate, and duration of response.

  PFS will be measured upon study completion via statistical analysis of the study data.

Study Arms (1)

ABT-263 + rituximab

EXPERIMENTAL

Drug: rituximab; Drug: ABT-263

Interventions

rituximab DRUG

IV infusion once weekly for four doses

Also known as: Rituxan

ABT-263 + rituximab

ABT-263 DRUG

ABT-263: oral solution or tablets, once daily dosing until disease progression

Also known as: navitoclax

ABT-263 + rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with a CD20-positive lymphoproliferative disorder (Revised European American Lymphoma \[REAL\]/World Health Organization \[WHO\]) and bi-dimensionally measurable disease with at least 1 lesion \>= 1.0 cm
• Eastern Cooperative Oncology Group (ECOG) performance score of \<= 1
• Adequate bone marrow function, independent of growth factor support (with the exception of participants with bone marrow that is heavily infiltrated with underlying disease \[80% or more\] who may use growth factor to achieve Absolute Neutrophil count (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.
• Participants 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 participants 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.
• Participant 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. Participants with Gilbert's Syndrome may have a Bilirubin \> 1.5 × ULN; activated partial thromboplastin time (aPTT), prothrombin time (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 obtained within 14 days prior to initial study drug administration, and prior to dosing on a urine obtained on Lead-in Day 1, if it has been \> 7 days since obtaining the serum pregnancy test results. 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 (minimum 1 complete menstrual cycle),a vasectomized partner, hormonal contraceptives for at least 3 months prior to study drug administration, or double-barrier method.

You may not qualify if:

• Participants 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.
• Participants' chemistry values must not exceed Grade 2. Grade 2 chemistry labs should be monitored at an increased frequency at the discretion of the investigator. Participants 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. Participants with Gilbert's Syndrome may be allowed to have a Bilirubin \> 3 × ULN based on a joint decision between the investigator and AbbVie medical monitor.
• 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 participant has an underlying, predisposing condition of bleeding or currently exhibits signs of clinically significant bleeding. The participanthas a recent history of non-chemotherapy induced thrombocytopenic associated bleeding within six months prior to the first dose of study drug. The participant 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 participant is pregnant or breast-feeding
• Participant has tested positive for HIV, Hepatitis B or Hepatitis C infection, (Participants 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.

Sponsors & Collaborators

• AbbVie: lead
• Genentech, Inc.: collaborator

Study Sites (6)

University of Arizona Cancer Center - North Campus /ID# 16721

Tucson, Arizona, 85719-1478, United States

Location

Stanford University School of Med /ID# 9782

Stanford, California, 94305-2200, United States

Location

Cleveland Clinic Main Campus /ID# 9784

Cleveland, Ohio, 44195, United States

Location

Univ of Wisconsin Hosp/Clinics /ID# 21701

Madison, Wisconsin, 53792-0001, United States

Location

Peter MacCallum Cancer Ctr /ID# 25067

Melbourne, Victoria, 3000, Australia

Location

The Royal Melbourne Hospital /ID# 9781

Parkville, Victoria, 3050, Australia

Location

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, B-Cell; Hematologic Neoplasms; Lymphoma, Non-Hodgkin

Interventions

Rituximab; navitoclax

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Lymphoma

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2008
• First Posted: November 11, 2008
• Study Start: July 21, 2009
• Primary Completion: February 7, 2025
• Study Completion: February 7, 2025
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); AU (2)