NCT02109224

Brief Summary

This phase I trial studies the side effects and best dose of ibrutinib in treating B-cell non-Hodgkin lymphoma that has returned or does not respond to treatment in patients with human immunodeficiency virus (HIV) infection. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether it is safe for patients with HIV infection to receive ibrutinib while also taking anti-HIV drugs.

Trial Health

57
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
72

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Sep 2014

Geographic Reach
1 country

7 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 7, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 9, 2014

Completed
5 months until next milestone

Study Start

First participant enrolled

September 1, 2014

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2015

Completed
Last Updated

August 20, 2015

Status Verified

April 1, 2015

Enrollment Period

10 months

First QC Date

April 7, 2014

Last Update Submit

August 18, 2015

Conditions

Outcome Measures

Primary Outcomes (2)

  • Incidence of toxicities assessed using National Cancer Institute (NCI) CTCAE version 4.0

    Up to 30 days

  • MTD of ibrutinib defined as the dose level in which no more than 1 out of 6 patients experiences a dose limiting toxicity assessed using NCI CTCAE version 4.0

    28 days

Secondary Outcomes (14)

  • 1-year OS

    From start of study treatment to death, assessed at 6 months

  • 1-year PFS

    From start of study treatment to relapse, progression, or death from any cause, whichever occurs first, assessed at 6 months

  • 6-month overall survival (OS)

    From start of study treatment to death, assessed at 6 months

  • 6-month progression free survival (PFS)

    From start of study treatment to relapse, progression, or death from any cause, whichever occurs first, assessed at 6 months

  • Changes in EBV DNA copy numbers in plasma and in PBMCs in relation to ibrutinib therapy

    Baseline to up to 30 days

  • +9 more secondary outcomes

Study Arms (1)

Treatment (ibrutinib)

EXPERIMENTAL

Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: IbrutinibOther: Laboratory Biomarker AnalysisOther: Pharmacological Study

Interventions

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, PCI-32765
Treatment (ibrutinib)

Correlative studies

Treatment (ibrutinib)

Correlative studies

Treatment (ibrutinib)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Known HIV infection and histologically confirmed B-cell non-Hodgkin lymphoma or B-cell lymphoproliferative disease as follows, as defined by the World Health Organization classification:
  • Active B-cell non-Hodgkin lymphoma (cluster of differentiation \[CD\]20 positive or negative), chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), or multiple myeloma that has relapsed, progressed, or been refractory to at least one regimen
  • Note: Patients with CLL, SLL, or mantle cell lymphoma (MCL) may only be enrolled in Stratum C
  • At least 14 days between ibrutinib initiation and last cancer therapy; any number of prior cancer therapies is permitted; patients otherwise fit for blood or marrow transplantation (BMT) should receive second-line chemotherapy before considering enrollment
  • Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive Western blot, or any other federally approved licensed HIV test; alternatively, this documentation may include a record that another physician has documented that the participant has HIV infection based on prior ELISA and Western blot, or other approved diagnostic tests
  • Participants must be on a stable antiretroviral regimen per current International Acquired Immunodeficiency Syndrome (AIDS) Society guidelines as follows, with no intention of changing the regimen within 8 weeks after ibrutinib initiation:
  • Choice of regimen: The specific antiretroviral agents are at physician discretion, and the use of investigational agents currently available on an expanded-access basis is allowed; use of experimental antiretroviral agents or those containing zidovudine (including Combivir and Trizivir) is prohibited
  • Patients with mantle cell lymphoma, CLL, or SLL must be on non-cytochrome P450, family 3, subfamily A, polypeptide 4 (CYPA3A4) modulating antiretroviral agents (Stratum C) to be eligible for this study
  • Patients may be switched to non-conflicting regimens in order to participate
  • Stability of regimen: With the exception of patients on zidovudine-based ART, any changes in antiretroviral regimen must be made at least 4 weeks prior to ibrutinib initiation; patients taking zidovudine-based ART must change to a non-zidovudine-based regimen at least 2 weeks prior to ibrutinib initiation; changes to ART therapy during the study may be made if medically necessary (e.g. toxicity, treatment failure)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (Karnofsky \>= 60%)
  • Life expectancy \>= 2 months
  • Absolute CD4+ lymphocyte count: \>= 75 cells/uL
  • Absolute neutrophil count \>= 750 cells/uL
  • Platelets \>= 50,000 cells/uL, or \>= 30,000/uL if bone marrow is involved by malignancy
  • +10 more criteria

You may not qualify if:

  • Prior exposure to ibrutinib
  • Receipt of any investigational agents within 14 days before the first dose of ibrutinib
  • Failure to recover to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 2 from clinically significant toxicities due to prior cancer therapies or to any investigational agents
  • Active central nervous system involvement by malignancy; central nervous system disease that has been treated into remission is permitted; a chart note of the clinician's impression of lack of central nervous system (CNS) involvement is acceptable
  • Patients who require concomitant treatment with CYP3A4/5 strong inhibitors or inducers OTHER than antiretroviral therapies for HIV
  • As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter product
  • A prednisone equivalent of \< 20 mg daily is permitted in patients requiring chronic use; larger doses must be discontinued \>= 7 days prior to ibrutinib initiation and are prohibited during study treatment
  • Anticoagulation with warfarin or equivalent vitamin K antagonists within 28 days prior to starting ibrutinib and throughout the study
  • Significant or uncontrolled intercurrent condition including, but not limited to:
  • Infection other than HIV, hepatitis B, or hepatitis C that is symptomatic or requires systemic treatment
  • Opportunistic infection within 60 days prior to enrollment
  • Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infection within 6 months prior to enrollment
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  • History of class B or class C cirrhosis, per the modified Child-Pugh classification
  • Psychiatric illness that would limit compliance
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

UCLA Center for Clinical AIDS Research and Education

Los Angeles, California, 90035, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Siteman Cancer Center at Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467-2490, United States

Location

MeSH Terms

Conditions

Burkitt LymphomaLeukemia, Lymphocytic, Chronic, B-CellLymphoma, B-Cell, Marginal ZoneHIV InfectionsIntraocular LymphomaMulti-centric Castleman's DiseasePrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticLymphoma, FollicularLymphoma, Mantle-CellLeukemia, Hairy CellMultiple MyelomaWaldenstrom Macroglobulinemia

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Epstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsBlood-Borne InfectionsCommunicable DiseasesSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesEye NeoplasmsNeoplasms by SiteNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Study Officials

  • Yvette Kasamon

    AIDS Malignancy Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 7, 2014

First Posted

April 9, 2014

Study Start

September 1, 2014

Primary Completion

July 1, 2015

Study Completion

July 1, 2015

Last Updated

August 20, 2015

Record last verified: 2015-04

Locations