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AzTrials

B Cell Non-Hodgkin's LymphomaPhase 1NCT01351935

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

A Phase 1 study testing AVL-292 in people with B Cell Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia, run by Celgene at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AVL-292
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
113 participants
Where
13 sitesUnited States
Study dates
18 Jul 2011to 26 Jun 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Northwestern University

    Chicago, Illinois, 60611

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Clearview Cancer Institute Oncology Specialties, P.C

    Huntsville, Alabama, 35805

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • University of California San Diego

    La Jolla, California, 92093-0960

  • Horizon Oncology Center

    Lafayette, Indiana, 47905

  • Mount Sinai School of Medicine and Mount Sinai Graduate School of Biological Sciences

    New York, New York, 10029

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • University of Texas Health Sciences Center

    San Antonio, Texas, 78229

  • US Oncology

    The Woodlands, Texas, 77380

  • University of Arizona SPORE

    Tucson, Arizona, 85719

Other trials in United States

About this study

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'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).

Read the 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.

Being tested
AVL-292
Keywords
non-hodgkin's lymphoma, lymphoma, leukemia, chronic lymphocytic leukemia, b-cell malignancies, Btk inhibitor, Phase 1b, Avila Therapeutics, Waldenstrom Macroglobulinemia
Medical subject headings
Lymphoma, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Waldenstrom Macroglobulinemia, Lymphoma, Non-Hodgkin, Lymphoma, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AVL-292Drug

    Also called Btk inhibitor

    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

Study groups in NCT01351935
Study groupRoleWhat they receive
AVL-292ExperimentalNot described
Receives: Drug: AVL-292

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety, tolerability,and dose limiting toxicities will be determined using AEs,PE,ophthalmologic examinations,clinical laboratory tests,vital signs, ECGs and echocardiograms/MUGA scans.

    Measured: with in the first 28 days after initiation of once daily oral dosing

Secondary outcomes (4)

  1. 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)

    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

    Measured: Completion of Part 1 dose escalation phase of study

  2. Evaluate the Pharmacokinetic parameters of AVL-292

    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.

    Measured: First 28 days of dosing

  3. Evaluate the Pharmacodynamics of AVL-292 by measurement of free Btk

    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.

    Measured: First 28 days of dosing

  4. Characterize preliminary anti-tumor efficacy of AVL-292 in relapsed and/or refractory B-NHL, CLL and WM

    Efficacy response assessments will be formally assessed within 7 days preceding C2D1, C3D1, C5D1, C7D1, and EOT

    Measured: After completion of 28 day cycle of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2011 (estimated)
  2. Study start18 Jul 2011
  3. Primary completion26 Jun 2015
  4. Study completion26 Jun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
113 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01351935
Sponsor's protocol ID
AVL-292-003
Status last verified
Nov 2019
First submitted
10 May 2011
Last updated
8 Nov 2019
Results posted
No
Data monitoring committee
No

Publications

  • Arnason JE, Brown JR. B cell receptor pathway in chronic lymphocytic leukemia: specific role of CC-292. Immunotargets Ther. 2014 Jan 24;3:29-38. doi: 10.2147/ITT.S37419. eCollection 2014.

    PubMed 27471698

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AVL-292 in people with B Cell Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia, run by Celgene at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01351935, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2019.

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