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.
Verified May 2011 by Avila Therapeutics

First Received on May 10, 2011.  
Last Updated on May 9, 2012  
History of Changes
This Clinical Trial Sponsored By: Avila Therapeutics
Collaborator: The Leukemia and Lymphoma Society
Information provided by (Responsible Party): Avila Therapeutics
ClinicalTrials.gov Identifier: NCT01351935
 

Purpose for Clinical Trial

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 Study Intervention Clinical Trial Phase
B Cell Non-Hodgkin’s Lymphoma
Chronic Lymphocytic Leukemia
Waldenstrom Macroglobulinemia
Drug: AVL-292 Phase 1

Study Type: Study Interventional
Study Design: Endpoint Classification: Safety Study
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:

Genetics Home Reference related topics:
aceruloplasminemia
hemophilia
MedlinePlus related topics:
Cancer
Chronic Lymphocytic Leukemia
Leukemia
Lymphoma

U.S. FDA Resources

Further study details as provided by Avila Therapeutics:

Primary Outcome Measures For Clinical Trial:

  • 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 For Clinical Trial:

  • 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

Estimated Enrollment: 60
Study Start Date: June 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Arms

Assigned Study 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, respirator

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