CD20-Positive Lymphoid Malignancies, Chronic Lymphoid Leukemia, Hematological Malignancies, Non-Hodgkin's Lymphoma
Conditions
Keywords
Non-Hodgkin's Lymphoma, Rituximab, Chronic Lymphoid Leukemia, Hematological Malignancies, ABT-263, Navitoclax, CD20-Positive Lymphoid Malignancies
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.
Interventions
DRUGrituximab
IV infusion once weekly for four doses
DRUGABT-263
ABT-263: oral solution or tablets, once daily dosing until disease progression
Sponsors
Genentech, Inc.
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. Inclusion Criteria (Extension Study) Participants 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. Participants entering the Extension Study must also have stable lab values per local laboratory reference ranges. In addition they must meet the following lab criteria: * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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. |
Countries
Australia, United States
Outcome results
None listed