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

• Register: ClinicalTrials.gov
• Last refreshed on: 7 January 2013
• Main ID: NCT00788684
• Date of registration: 10/11/2008
• Primary sponsor: AbbVie (prior sponsor, Abbott)
• Public title: Safety Study of ABT-263 in Combination With Rituximab in Lymphoid Cancers
• Scientific title: A Phase 1 Study Evaluating the Safety of ABT-263 in Combination With Rituximab in Subjects With CD20-positive Lymphoid Malignancies
• Date of first enrolment: July 2009
• Target sample size: 36
• Recruitment status: Active, not recruiting
• URL: http://clinicaltrials.gov/show/NCT00788684
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Australia, United States

Contacts

• Name: Sari Enschede, MD
• Affiliation: AbbVie

Key inclusion & exclusion criteria

Inclusion Criteria

- >or = 18 years of age

- 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
- 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

CD20-Positive Lymphoid Malignancies

Chronic Lymphoid Leukemia

Hematological Malignancies

Non-Hodgkin's Lymphoma

Intervention(s)

Drug: ABT-263

Drug: rituximab

Primary Outcome(s)

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 Outcome(s)

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.]

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.]

Secondary ID(s)

M10-166

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Genentech