Overview

This trial is active, not recruiting.

Conditions cd20-positive lymphoid malignancies, chronic lymphoid leukemia, hematological malignancies, non-hodgkin's lymphoma
Treatments abt-263, rituximab
Phase phase 1
Targets BCL-2, CD20
Sponsor AbbVie (prior sponsor, Abbott)
Collaborator Genentech, Inc.
Start date July 2009
End date September 2018
Trial size 36 participants
Trial identifier NCT00788684, M10-166

Summary

This is a Phase 1 study evaluating the safety of ABT-263 administered in combination with rituximab in subjects with CD20-positive lymphoproliferative disorders. The extension portion of the study will allow active subjects to continue to receive ABT-263 for up to 7 years after the last subject transitions with quarterly study evaluations.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
abt-263 navitoclax
ABT-263: oral solution or tablets, once daily dosing until disease progression
rituximab Rituxan
IV infusion once weekly for four doses

Primary Outcomes

Measure
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).
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
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.

Secondary Outcomes

Measure
Preliminary progression-free survival (PFS), response rate, and duration of response.
time frame: PFS will be measured upon study completion via statistical analysis of the study data.
Extension Study: Continued assessment of the preliminary progression-free survival (PFS), response rate, and duration of response.
time frame: PFS will be measured upon study completion via statistical analysis of the study data.

Eligibility Criteria

Male or female participants from 18 years up to 99 years old.

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 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.

Additional Information

Official title A Phase 1 Study Evaluating the Safety of ABT-263 in Combination With Rituximab in Subjects With CD20-positive Lymphoid Malignancies
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by AbbVie.