Clinical trial NCT01351935: Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia
Official title: Phase 1b, Escalating Dose Study of AVL-292, a Bruton's Tyrosine Kinase (Btk) Inhibitor, as Monotherapy in Subjects With Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B Cell Non-Hodgkin's Lymphoma
Chronic Lymphocytic Leukemia
Waldenstrom Macroglobulinemia
Keywords: non-hodgkin's lymphoma
lymphoma
leukemia
chronic lymphocytic leukemia
b-cell malignancies
Btk inhibitor
Phase 1b
Avila Therapeutics
Waldenstrom Macroglobulinemia
Lead sponsor: Celgene
Sponsor class: INDUSTRY
Collaborators: name: The Leukemia and Lymphoma Society
First posted: 2011-05-11
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Safety, tolerability,and dose limiting toxicities will be determined using AEs,PE,ophthalmologic examinations,clinical laboratory tests,vital signs, ECGs and echocardiograms/MUGA scans.
timeFrame: with in the first 28 days after initiation of once daily oral dosing
Secondary outcomes:
measure: 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)
timeFrame: Completion of Part 1 dose escalation phase of study
measure: Evaluate the Pharmacokinetic parameters of AVL-292
timeFrame: First 28 days of dosing
measure: Evaluate the Pharmacodynamics of AVL-292 by measurement of free Btk
timeFrame: First 28 days of dosing
measure: Characterize preliminary anti-tumor efficacy of AVL-292 in relapsed and/or refractory B-NHL, CLL and WM
timeFrame: After completion of 28 day cycle of treatment
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Institute Oncology Specialties, P.C
state: Alabama
city: Tucson
country: United States
facility: University of Arizona SPORE
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Lafayette
country: United States
facility: Horizon Oncology Center
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai School of Medicine and Mount Sinai Graduate School of Biological Sciences
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Sciences Center
state: Texas
city: The Woodlands
country: United States
facility: US Oncology
state: Texas
Study officials:
References:
citation: Arnason JE, Brown JR. B cell receptor pathway in chronic lymphocytic leukemia: specific role of CC-292. Immunotargets Ther. 2014 Jan 24;3:29-38. doi: 10.2147/ITT.S37419. eCollection 2014.