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

May 10, 2011
February 26, 2014
June 2011
December 2015   (final data collection date for primary outcome 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. [ Time Frame: with in the first 28 days after initiation of once daily oral dosing ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01351935 on ClinicalTrials.gov Archive Site
  • 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
  • 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 ]
    Efficay response assessments will be formally assessed within 7 days preceding C2D1, C3D1, C5D1, C7D1, and EOT
Not Provided
Not Provided
 
Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia
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

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).

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • B Cell Non-Hodgkin's Lymphoma
  • Chronic Lymphocytic Leukemia
  • Waldenstrom Macroglobulinemia
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
Experimental: AVL-292
Intervention: Drug: AVL-292
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
December 2015
December 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Markus Kocher, PhD mkocher@celgene.com
Contact: Heather Lounsbury 781-541-3724 AVLclinicaltrials@avilatx.com
United States
 
NCT01351935
AVL-292-003
No
Celgene Corporation
Celgene Corporation
The Leukemia and Lymphoma Society
Not Provided
Celgene Corporation
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP