Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia
- Conditions
- Chronic Lymphocytic LeukemiaWaldenstrom MacroglobulinemiaB Cell Non-Hodgkin's Lymphoma
- Interventions
- Registration Number
- NCT01351935
- Lead Sponsor
- Celgene
- Brief Summary
The purpose of this study is to evaluate the safety and tolerability of AVL-292 as monotherapy in subjects with relapsed or refractory B cell non-Hodgkin lymphoma (B-NHL), chronic lymphocytic leukemia (CLL) or Waldenstrom's macroglobulinemia (WM).
- Detailed Description
Bruton's tyrosine kinase (Btk) is non-receptor tyrosine kinase with restricted cellular expression largely limited to B-lymphocytes, monocytes, and mast cells or basophils. Btk is a critical component of the B cell receptor (BCR) signaling network and is crucial for B cell development. Investigation has revealed that some B cell lymphomas and CLL depend on BCR signaling, suggesting that interruption of such signaling could be a promising therapeutic opportunity in B-NHL, CLL and WM.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 113
-
Women and men ≥18 years of age
-
Body weight ≥50 kg.
-
Confirmed diagnosis of B cellNon-Hodgkin Lymphoma(according to World Health Organization [WHO] classification)including Chronic Lymphocytic Leukemia/Small cell Lymphocytic Leukemia (International Workshop),or Waldenstrom's Macroglobulinemia(Second International Workshop)
-
Have failed ≥1 previous treatment for B-NHL/CLL/WM, and have relapsed or refractory disease following last prior treatment.
-
Eastern Cooperative Oncology Group performance status of ≤ 2 and a life expectancy of at least 3 months.
-
Ability to swallow oral capsules without difficulty
-
Has recovered from adverse toxic effects of prior therapies
-
Meet the following clinical laboratory requirements:
- Creatinine ≤ 1.5 × upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 x ULN
- AST and ALT ≤ 3 × ULN
- Platelet count ≥ 50,000/µL (non-hodgkin & Waldenstrom's)
- Platelet count ≥ 30,000/µL (chronic lymphocytic leukemia)
- Absolute Neutrophil count ≥ 1000/µL
- Prior allogeneic bone marrow transplant
- Autologous stem cell transplant within 3 months of screening
- Active central nervous system involvement
- Subjects with autoimmune hemolytic anemia or immune thrombocytopenia
- Prior treatment with a Btk inhibitor
- Active uncontrolled infection
- History of malabsorption
- Uncontrolled illness, i.e cardiac, endocrine, respiratory, etc.
- History of myocardial infarction, acute coronary syndromes, coronary angioplasty and/or stenting with in the previous 6 months
- History of another currently active cancer
- History of major surgery within 4 weeks or minor surgery within 1 week
- Other medical or psychiatric illness or organ dysfunction
- HIV positive
- Positive for Hepatitis B surface antigen or Hepatitis C-virus
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AVL-292 AVL-292 -
- Primary Outcome Measures
Name Time Method Safety, tolerability,and dose limiting toxicities will be determined using AEs,PE,ophthalmologic examinations,clinical laboratory tests,vital signs, ECGs and echocardiograms/MUGA scans. with in the first 28 days after initiation of once daily oral dosing
- Secondary Outcome Measures
Name Time Method Establish recommended Phase 2 dose, after completing dose escalation in Part 1 and evaluating accumulated safety,PK,and PD data from the dose escalation phase (Part1) Completion of Part 1 dose escalation phase of study After completion of observation for dose limiting toxicities in Part 1 of the study, the accumulated safety, PK, and PD data from Part 1 will be evaluated by the investigators and Sponsor to select a preliminary RP2D for administration to additional subjects to be enrolled into 1 of 3 independent and non-randomized diagnosis-specific expansion cohorts in Part 2 of the study
Evaluate the Pharmacokinetic parameters of AVL-292 First 28 days of dosing Serial blood sampling to enable PK characterization of AVL-292 will be performed for the Cycle1 Day 1 (C1D1) and Cycle 1Day 15 dose administrations. Additional samples will be obtained on C1D8 and C1D22.A non-compartmental model will be evaluated for all subjects.
Evaluate the Pharmacodynamics of AVL-292 by measurement of free Btk First 28 days of dosing The PD activity of AVL-292 will be studied with a quantitative assay using a covalent probe to directly assess free Btk in PBMC lysates.
Characterize preliminary anti-tumor efficacy of AVL-292 in relapsed and/or refractory B-NHL, CLL and WM After completion of 28 day cycle of treatment Efficacy response assessments will be formally assessed within 7 days preceding C2D1, C3D1, C5D1, C7D1, and EOT
Trial Locations
- Locations (13)
University of Arizona SPORE
🇺🇸Tucson, Arizona, United States
Clearview Cancer Institute Oncology Specialties, P.C
🇺🇸Huntsville, Alabama, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Mount Sinai School of Medicine and Mount Sinai Graduate School of Biological Sciences
🇺🇸New York, New York, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Horizon Oncology Center
🇺🇸Lafayette, Indiana, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Texas Health Sciences Center
🇺🇸San Antonio, Texas, United States
US Oncology
🇺🇸The Woodlands, Texas, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States