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

November 6, 2019 updated by: Celgene

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

113

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Huntsville, Alabama, United States, 35805
        • Clearview Cancer Institute Oncology Specialties, P.C
    • Arizona
      • Tucson, Arizona, United States, 85719
        • University of Arizona SPORE
    • California
      • La Jolla, California, United States, 92093-0960
        • University of California San Diego
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic Jacksonville
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Indiana
      • Lafayette, Indiana, United States, 47905
        • Horizon Oncology Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai School of Medicine and Mount Sinai Graduate School of Biological Sciences
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Sciences Center
      • The Woodlands, Texas, United States, 77380
        • US Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Btk inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
with in the first 28 days after initiation of once daily oral dosing

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
Completion of Part 1 dose escalation phase of study
Evaluate the Pharmacokinetic parameters of AVL-292
Time Frame: 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.
First 28 days of dosing
Evaluate the Pharmacodynamics of AVL-292 by measurement of free Btk
Time Frame: 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.
First 28 days of dosing
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
Efficacy response assessments will be formally assessed within 7 days preceding C2D1, C3D1, C5D1, C7D1, and EOT
After completion of 28 day cycle of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celgene

Collaborators

The Leukemia and Lymphoma Society

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 18, 2011

Primary Completion (ACTUAL)

June 26, 2015

Study Completion (ACTUAL)

June 26, 2015

Study Registration Dates

First Submitted

May 10, 2011

First Submitted That Met QC Criteria

May 10, 2011

First Posted (ESTIMATE)

May 11, 2011

Study Record Updates

Last Update Posted (ACTUAL)

November 8, 2019

Last Update Submitted That Met QC Criteria

November 6, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AVL-292-003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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