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B-Cell LymphomaPhase 1PCYC-04753NCT00849654

Study of the Safety and Tolerability of PCI-32765 in Patients With Recurrent B Cell Lymphoma

A Phase 1 study testing PCI-32765 in people with B-Cell Lymphoma and B-Cell Leukemia, run by Pharmacyclics LLC. at 9 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 establish the safety and optimal dose of orally administered PCI-32765 in patients with recurrent B cell lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
B-Cell Lymphoma, B-Cell Leukemia
What is being tested?
PCI-32765
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
9 sitesUnited States
Study dates
Feb 2009to Jul 2012
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. There is no experience with this drug in a pediatric population.
  • Body weight ≥ 40 kg.
  • Recurrent surface immunoglobulin positive B cell non-Hodgkin's lymphoma (NHL) according to WHO classification, including small lymphocytic lymphoma/ chronic lymphocytic leukemia (SLL/CLL) lymphoplasmacytic lymphoma, including Waldenström's Macroglobulinemia (WM), and pre-identified DLBCL ABC subtype oFor the DLBCL-ABC cohort, documented, activated B-cell subtype by either immunohistochemistry or tissue microarray analysis.
  • Measurable disease (for NHL, bidimensional disease ≥ 2 cm diameter in at least one dimension, for CLL ≥ 5000 leukemia cells/mm3, for WM presence of immunoglobulin M paraprotein with a minimum IgM level ≥ 1000 mg/dL and infiltration of bone marrow by lymphoplasmacytic cells), and pre-identified DLBCL ABC subtype by immunohistochemistry (IHC).
  • Have failed ≥ 1 previous treatment for lymphoma and no standard therapy is available. Patients with diffuse large B cell lymphoma must have failed, refused or be ineligible for autologous stem cell transplant.
  • ECOG performance status of ≤ 1.
  • Ability to swallow oral capsules without difficulty.
  • Willing and able to sign a written informed consent.

Who cannot join

  • More than four prior systemic therapies (not counting maintenance rituximab), except for CLL patients. Salvage therapy/conditioning regimen leading up to autologous bone marrow transplantation is considered to be one regimen (This inclusion criterion does not apply to the DLBCL-ABC cohort).
  • Prior allogeneic bone marrow transplant.
  • Immunotherapy, chemotherapy, radiotherapy or experimental therapy within 4 weeks before first day of study drug dosing.
  • Major surgery within 4 weeks before first day of study drug dosing.
  • CNS involvement by lymphoma.
  • Active opportunistic infection or treatment for opportunistic infection within 4 weeks before first day of study drug dosing.
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  • History of malabsorption.
  • Laboratory abnormalities:
  • Creatinine > 1.5 × institutional upper limit of normal (ULN)
  • Total bilirubin > 1.5 x institutional ULN (unless elevated from documented Gilbert's syndrome)
  • AST or ALT > 2.5 × institutional ULN
  • Platelet count < 75,000/µL (unless patients have CLL and bone-marrow involvement, provided they are not transfusion-dependent)
  • Absolute neutrophil count (ANC) < 1500/µL (unless patients have CLL and bone-marrow involvement)
  • Hgb < 8.0 g/dL
  • Uncontrolled illness including but not limited to: ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric illness that would limit compliance with study requirements.
  • Risk factors for, or use of medications known to prolong QTc interval or that may be associated with Torsades de Pointes within 7 days of treatment start.
  • QTc prolongation (defined as a QTc > 450 msecs) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). If the screening ECG has a QTc > 450 msecs, the ECG can be submitted for a centralized, cardiologic evaluation.
  • History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within the past 6 months.
  • Known HIV infection.
  • Hepatitis B sAg or Hepatitis C positive.
  • Other medical or psychiatric illness or organ dysfunction which, in the opinion of the investigator, would either compromise the patient's safety or interfere with the evaluation of the safety of the study agent.
  • Pregnant or lactating women (female patients of child-bearing potential must have a negative serum pregnancy test within 14 days of first day of drug dosing, or, if positive, a pregnancy ruled out by ultrasound).
  • Women of child-bearing potential or sexually active men, unwilling to use adequate contraceptive protection during the course of the study.
  • History of prior cancer < 2 years ago, except for basal cell or squamous cell carcinoma of the skin, cervical cancer in situ or other in situ carcinomas.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • National Cancer Institute

    Bethesda, Maryland, 20892-1203

  • University of Vermont College of Medicine

    Burlington, Vermont, 05405

  • University of Chicago

    Chicago, Illinois, 60637

  • Willamette Valley Cancer Institute/Research Ctr

    Eugene, Oregon, 97401

  • University of Texas, MD Anderson

    Houston, Texas, 77030

  • New York Prebyterian Hospital Cornell Medical Center

    New York, New York, 10065

  • Stanford University School of Medicine

    Palo Alto, California, 94305

  • Northwest Cancer Specialists, Vancouver Cancer Center

    Vancouver, Washington, 98684

  • Yakima Valley Memorial Hospital/North Star Lodge Cancer Ctr

    Yakima, Washington, 98902

Other trials in United States

About this study

Official title: Phase I Dose-Escalation Study of Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Recurrent B Cell Lymphoma

The purpose of this study is to establish the safety and optimal dose of orally administered PCI-32765 in patients with recurrent B cell lymphoma.

Being tested
PCI-32765
Keywords
PCI-32765, Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Burkitt Lymphoma, Lymphoma, B-Cell, Marginal Zone, Lymphoma, B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle Cell, Leukemia, Lymphoid, Leukemia, B-Cell, Waldenstrom macroglobulinemia, Bruton's Tyrosine Kinase
Medical subject headings
Lymphoma, B-Cell, Leukemia, B-Cell, Lymphoma, Lymphoma, Non-Hodgkin, Burkitt Lymphoma, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, Lymphoma, Mantle-Cell

What participants receive

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

  • PCI-32765Drug

    In the dose-escalation cohorts, PCI-32765 will be administered in 1.25, 2.5, 5.0, 8.3, 12.5, and 17.5 mg/kg/d dose orally once per day for 28 days followed by a 7-day rest period to determine the MTD. If MTD is not reached, dosing levels may be increased beyond 17.5mg/kg/d by 33% increments.

    In the continuous dosing cohorts, PCI-32765 will be administered in 8.3 mg/kg/day and 560 mg/day (fixed dose) dose orally once per day for 35 days.

Study groups in NCT00849654
Study groupRoleWhat they receive
PCI-32765ExperimentalNot described
Receives: Drug: PCI-32765

What is being measured

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

  1. Dose limiting toxicity assessment for each patient.

    Measured: At the end of the first 35 day cycle

  2. Adverse events

    Measured: 30 days after last dose of study drug

  3. Pharmacokinetic/ Pharmacodynamic assessments

    Measured: during Cycle 1

Secondary outcomes (1)

  1. Tumor response

    Measured: at the end of Cycles 2, 4, and 6 unitl progression

Timeline

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

  1. First posted24 Feb 2009 (estimated)
  2. Study startFeb 2009
  3. Primary completionJul 2012
  4. Study completionJul 2012

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00849654
Sponsor's protocol ID
PCYC-04753
Acronym
PCYC-04753
Status last verified
May 2013
First submitted
20 Feb 2009
Last updated
22 May 2013
Results posted
No
Data monitoring committee
No

Publications

  • Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015 Aug;21(8):922-6. doi: 10.1038/nm.3884. Epub 2015 Jul 20.

    PubMed 26193343

  • Marostica E, Sukbuntherng J, Loury D, de Jong J, de Trixhe XW, Vermeulen A, De Nicolao G, O'Brien S, Byrd JC, Advani R, McGreivy J, Poggesi I. Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies. Cancer Chemother Pharmacol. 2015 Jan;75(1):111-21. doi: 10.1007/s00280-014-2617-3. Epub 2014 Nov 8.

    PubMed 25381051

  • Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013 Jan 1;31(1):88-94. doi: 10.1200/JCO.2012.42.7906. Epub 2012 Oct 8.

    PubMed 23045577

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PCI-32765 in people with B-Cell Lymphoma and B-Cell Leukemia, run by Pharmacyclics LLC. at 9 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 8 inclusion and 24 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 22 May 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 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?

Dose limiting toxicity assessment for each patient. (time frame: At the end of the first 35 day cycle). The study lists 3 primary outcomes in all. 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 NCT00849654, which also lists 3 linked publications.

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 22 May 2013.

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