amg 319 lymphoid malignancy fih

Conditions: Cancer; Chronic Lymphocytic Leukemia; Diffuse Large Cell Lymphoma; Hematologic Malignancies; Hematology; Leukemia; Low Grade Lymphoma; Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Oncology; Oncology Patients; T Cell Lymphoma; Tumors

Summary: this is a multi-center, phase 1, open-label first-in-human study of amg 319 in subjects with relapsed or refractory lymphoid malignancies. this study consists of two parts. the dose exploration in part 1, studies cohorts of 3 subjects with relapsed or refractory lymphoid malignancies and uses a practical continuous reassessment model \[crm\] to guide dose escalation and to define the mtd. the dose expansion in part 2 will enroll 20 subjects with cll at a dose no higher than the mtd and further explore the safety, pk, and clinical activity of amg 319 in this patient population.


Eligibility criteria:
inclusion criteria: - part 1 (dose exploration): relapsed or refractory lymphoid malignancy of the following type for which standard treatment does not exist or is no longer effective: b-cell chronic lymphocytic leukemia (cll) confirmed by immunophenotype or non-hodgkin lymphoma: low or intermediate grade b-cell nhl, mantle cell lymphoma, non-cutaneous t-cell nhl confirmed by histology and/or immunophenotype * part 2 (dose expansion): subjects must have relapsed or refractory b-cell chronic lymphocytic leukemia confirmed by immunophenotype for which standard treatment does not exist or is no longer effective. * eastern cooperative oncology group (ecog) performance status ≤ 2 * life expectancy of \> 3 months, in the opinion of the investigator * men or women ≥ 18 years old * hematological function, as follows: absolute neutrophil count (anc) ≥ 1.5 x 109/l (unless due to disease-related bone marrow involvement as documented by bone marrow biopsy, ≥ 0.5 x 109/l) platelet count ≥ 50 x 109/l (without a transfusion within 14 days before enrollment) hemoglobin ≥ 9 g/dl - hepatic function, as follows: aspartate aminotransferase (ast) \< 3.0 x uln alanine aminotransferase (alt) \< 3.0 x uln alkaline phosphatase (alp) \< 2.0 x uln (\< 5 x uln in subjects whom the pi and sponsor agree that clinical data suggest an extrahepatic source of elevation) total bilirubin \< 1.5 x uln (\< 3.0 x uln for subjects with documented gilbert's disease or for whom the indirect bilirubin level suggests an extrahepatic source of elevation) amylase ≤ 2.0 x iuln lipase ≤ 2.0 x iuln exclusion criteria: * primary or disseminated tumor involving the central nervous system (cns) * a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years * history of allogeneic stem-cell (or other organ) transplantation * clinically significant ecg changes which obscure the ability to assess the pr, qt, and qrs interval; congenital long qt syndrome * qtcf interval \> 470 msec * active or chronic hepatitis b or hepatitis c infection, determined by serologic tests * recent infection requiring intravenous anti-infective treatment that was completed ≤ 14 days before enrollment

Keywords: low intermediate grade b cell lymphoma non-cutaneous t-cell nhl mantle cell lymphoma pi3k delta lymphoid nhl mcl hematologic cll chronic lymphocytic leukemia