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
Sponsor:
Avila Therapeutics
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Avila Therapeutics
ClinicalTrials.gov Identifier:
NCT01351935
First received: May 10, 2011
Last updated: September 7, 2012
Last verified: May 2011
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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 Avila Therapeutics:
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 ]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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01351935
Contacts
| Contact: Kathryn Stiede | 781-541-3741 | AVLclinicaltrials@avilatx.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
Avila Therapeutics
The Leukemia and Lymphoma Society
More Information
Additional Information:
No publications provided
| Responsible Party: | Avila Therapeutics |
| ClinicalTrials.gov Identifier: | NCT01351935 History of Changes |
| Other Study ID Numbers: | AVL-292-003 |
| Study First Received: | May 10, 2011 |
| Last Updated: | September 7, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Avila Therapeutics:
|
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 May 16, 2013