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

Status:	Active, not recruiting
Conditions:	Blood Cancer, Lymphoma, Hematology
Therapuetic Areas:	Hematology, Oncology
Healthy:	No
Age Range:	18 - 99
Updated:	3/7/2019
Start Date:	July 21, 2009
End Date:	April 30, 2020

A Phase 1 Study Evaluating the Safety of ABT-263 in Combination With Rituximab in Subjects With CD20-positive Lymphoid Malignancies

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 9 years
after the last subject transitions with quarterly study evaluations.

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
- 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 norma

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.

We found this trial at

sites

University of Arizona Cancer Center /ID# 16721

1501 North Campbell Avenue
Tucson, Arizona 85724

from

Tucson, AZ