Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Celgene Corporation
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01351935
First received: May 10, 2011
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

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).


Condition Intervention Phase
B Cell Non-Hodgkin's Lymphoma
Chronic Lymphocytic Leukemia
Waldenstrom Macroglobulinemia
Drug: AVL-292
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Safety, tolerability,and dose limiting toxicities will be determined using AEs,PE,ophthalmologic examinations,clinical laboratory tests,vital signs, ECGs and echocardiograms/MUGA scans. [ Time Frame: with in the first 28 days after initiation of once daily oral dosing ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) [ Time Frame: Completion of Part 1 dose escalation phase of study ] [ Designated as safety issue: No ]
    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 [ Time Frame: First 28 days of dosing ] [ Designated as safety issue: No ]
    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 [ Time Frame: First 28 days of dosing ] [ Designated as safety issue: No ]
    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 [ Time Frame: After completion of 28 day cycle of treatment ] [ Designated as safety issue: No ]
    Efficacy response assessments will be formally assessed within 7 days preceding C2D1, C3D1, C5D1, C7D1, and EOT


Estimated Enrollment: 60
Study Start Date: June 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AVL-292 Drug: AVL-292
125 mg to 625 mg orally, once a day, for 28 days (28 days equals 1 cycle). Number of cycles: until progression or unacceptable toxicity develops
Other Name: Btk inhibitor

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01351935

Contacts
Contact: Markus Kocher, PhD mkocher@celgene.com
Contact: Heather Lounsbury 781-541-3724 AVLclinicaltrials@avilatx.com

Locations
United States, Alabama
Clearview Cancer Institute Recruiting
Huntsville, Alabama, United States, 35805
Contact: Pauli       emily.pauli@ccihsv.com   
Principal Investigator: Schreeder, MD         
United States, Arizona
University of Arizona (SPORE) Recruiting
Tucson, Arizona, United States, 85719
Contact    520-694-9050      
Principal Investigator: Tom Miller, MD         
United States, California
Moores UCSD Cancer Center Recruiting
San Diego, California, United States, 92093
Contact: Sheila Hoff    858-822-5360    shoff@ucsd.edu   
Principal Investigator: Thomas Kipps, MD         
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
Contact: Hanlon    904-953-2946    hanlon.james@mayo.edu   
Principal Investigator: James Foran, MD         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Patton    312-695-1377    d-patton2@northwestern.edu   
Principal Investigator: Shou MA, MD         
United States, Indiana
Horizon Oncology Center Recruiting
Lafayette, Indiana, United States, 47905
Contact    765-446-5111      
Principal Investigator: Wael Harb, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact    617-632-6840      
Principal Investigator: Jennifer Brown, MD         
United States, New York
Mount Sinai School of Medicine & Mount Sinai Graduate School of biological Sciences Recruiting
New York, New York, United States, 10029
Contact    212-241-9650      
Principal Investigator: Janice Gabrilove, MD         
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Principal Investigator: Paul Barr, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Jenny Bates    216-445-3796    jarvisj@ccf.org   
Principal Investigator: Brian Hill, MD         
United States, Oregon
US Oncology Research: Willamette Valley Cancer Institute and Research Center Recruiting
Springfield, Oregon, United States, 97477
Contact: Jeanne Schaffer    541-741-3451      
Principal Investigator: Jeff Sharman, MD         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Lynette Alexander    713-792-6989    LYAlexander@mdanderson.org   
Principal Investigator: Jan Burger, MD         
University of Texas Health Science Center, San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Medina    210-450-1789    medinag3@uthscsa.edu   
Principal Investigator: Kevin Kelly, MD         
Sponsors and Collaborators
Celgene Corporation
The Leukemia and Lymphoma Society
  More Information

Additional Information:
No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01351935     History of Changes
Other Study ID Numbers: AVL-292-003
Study First Received: May 10, 2011
Last Updated: February 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
non-hodgkin's lymphoma
lymphoma
leukemia
chronic lymphocytic leukemia
b-cell malignancies
Btk inhibitor
Phase 1b
Avila Therapeutics
Waldenstrom Macroglobulinemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Waldenstrom Macroglobulinemia
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on July 24, 2014