AzTrials
AzTrials

Adult B Acute Lymphoblastic LeukemiaPhase 1NCT02109224

Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection

A Phase 1 study testing Ibrutinib, Laboratory Biomarker Analysis and Pharmacological Study in people with Adult B Acute Lymphoblastic Leukemia and Chronic Lymphocytic Leukemia, run by National Cancer Institute (NCI) at 7 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ibrutinib, Laboratory Biomarker Analysis and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
7 sitesUnited States
Study dates
Sep 2014to Jul 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

  • 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:
Show all 25Show fewer
  • 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
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x institutional upper limit of normal (ULN), or =< 5.0 x ULN if attributable to malignancy
  • Total bilirubin =< 2.0 x ULN, unless elevated bilirubin is attributable to Gilbert's syndrome or to HIV medications (e.g., indinavir, tenofovir, atazanavir)
  • Creatinine clearance (CrCl) >= 40 mL/min (modified Cockcroft-Gault)
  • All subjects must be screened for hepatitis B and C infection; subjects must either have no history of hepatitis B or C, or must meet the following criteria in order to e eligible:
  • Hepatitis B: Subjects infected with hepatitis B must receive anti-hepatitis B therapy; per Infectious Diseases Society of America (IDSA) and American Association for the Study of Liver Diseases (AASLD) guidelines, subjects that show no immunity, defined by the lack of hepatitis B surface antibody, and show evidence of chronic infection (i.e. hepatitis B surface antigen positive [HBsAg+], hepatitis B core antibody positive [HB core AB +], hepatitis B surface antibody negative [HBsAB-]) must be on anti-hepatitis B therapy throughout the study in order to be eligible; the exact hepatitis B therapy is at the discretion of the infection disease specialist or investigator; all patients diagnosed with hepatitis B must also meet the liver function test criteria listed above and have no evidence of cirrhosis; however, all patients who present with acute hepatitis B, or who show normal transaminases but are HBsAg+ and immunoglobulin M positive (IgM+) for hepatitis B core antigen, are ineligible
  • Hepatitis C: Subjects, who are hepatitis C antibody positive, with or without a positive hepatitis C ribonucleic acid (RNA) level, must meet the liver function test criteria listed above and have no evidence of cirrhosis; patients diagnosed with hepatitis C less than 6 months before enrollment will be considered to have acute hepatitis C and will be ineligible unless the hepatitis C viral load is undetectable
  • Must in the opinion of the investigator be capable of complying with this protocol
  • Patients may not begin protocol therapy within 7 days of major surgery or within 3 days of minor surgery
  • Willingness of sexually active subjects to use adequate contraception; both men and women of child-bearing potential treated or enrolled on this study must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry, for the duration of study participation, and 4 months after completion of ibrutinib; men who only have sex with other men do not need to use contraception specifically for this study; (should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately)
  • Ability to understand and willingness to sign a written informed consent document

Who cannot join

  • 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
Show all 23Show fewer
  • 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
  • Inability to swallow capsules whole, or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption, such as malabsorption syndrome, small bowel resection, or poorly controlled inflammatory bowel disease affecting the small intestine
  • History of prior malignancy, with the exception of the following:
  • Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
  • Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
  • Adequately treated cervical carcinoma in situ without current evidence of disease
  • Skin-limited Kaposi sarcoma that has not required systemic treatment within 6 months prior to study enrollment
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib
  • Pregnancy or breastfeeding; a pregnancy test must be performed within 7 days prior to ibrutinib initiation in women of childbearing potential; pregnant women are excluded; breastfeeding must be discontinued

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites
  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • UCLA Center for Clinical AIDS Research and Education

    Los Angeles, California, 90035

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Siteman Cancer Center at Washington University

    St Louis, Missouri, 63110

  • Albert Einstein College of Medicine

    The Bronx, New York, 10461

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467-2490

Other trials in United States

About this study

Official title: Phase I and Pharmacokinetic Study of Ibrutinib in HIV-Infected Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Multiple Myeloma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and tolerability of single-agent ibrutinib in combination with antiretroviral therapy (ART) specifically with respect to ibrutinib metabolism in HIV-infected patients with relapsed or refractory B-cell neoplasms.

II. To determine the maximum tolerated dose (MTD) of ibrutinib in this setting.

SECONDARY OBJECTIVES:

  1. To characterize ibrutinib pharmacokinetics in relation to ART-cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) interactions.

II. To describe toxicity in relation to plasma concentrations of ibrutinib and its main metabolite.

III. To estimate objective response rate, clinical benefit, times to tumor response and progression, and 6-month and 1-year progression-free and overall survival.

IV. To describe changes in HIV viral load, immunologic parameters, and Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) deoxyribonucleic acid (DNA) copy numbers in plasma and in peripheral blood mononuclear cells (PBMC) in relation to ibrutinib therapy.

OUTLINE: This is a dose-escalation study.

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

After completion of study treatment, patients are followed up at 30 days.

Being tested
Ibrutinib, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings
Burkitt Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, HIV Infections, Intraocular Lymphoma, Multi-centric Castleman's Disease, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, PCI-32765

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT02109224
Study groupRoleWhat they receive
Treatment (ibrutinib)ExperimentalPatients 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.
Receives: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

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

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

    Measured: Up to 30 days

  2. 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

    Measured: 28 days

Secondary outcomes (14)
  1. 1-year OS

    Probabilities of 1-year OS will be estimated with the Kaplan-Meier method and reported with 95% CI.

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

  2. 1-year PFS

    Probabilities of 1-year PFS will be estimated with the Kaplan-Meier method and reported with 95% CI.

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

  3. 6-month overall survival (OS)

    Probabilities of 6-month OS will be estimated with the Kaplan-Meier method and reported with 95% CI.

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

  4. 6-month progression free survival (PFS)

    Probabilities of 6-month PFS will be estimated with the Kaplan-Meier method and reported with 95% CI.

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

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

    Changes will be analyzed with descriptive statistics. Where there are sufficient data, repeated measures analysis of variance will be used to assess the effect of ibrutinib on these parameters across time. If the data do not meet the assumptions of normality, the data will either be transformed or Friedman's test (i.e. non-parametric analogue to a repeated measures analysis of variance) will be used.

    Measured: Baseline to up to 30 days

  6. Changes in HHV-8 DNA copy numbers in plasma and in PBMCs in relation to ibrutinib therapy

    Changes will be analyzed with descriptive statistics. Where there are sufficient data, repeated measures analysis of variance will be used to assess the effect of ibrutinib on these parameters across time. If the data do not meet the assumptions of normality, the data will either be transformed or Friedman's test (i.e. non-parametric analogue to a repeated measures analysis of variance) will be used.

    Measured: Baseline to up to 30 days

  7. Changes in HIV viral load

    Changes will be analyzed with descriptive statistics. Where there are sufficient data, repeated measures analysis of variance will be used to assess the effect of ibrutinib on these parameters across time. If the data do not meet the assumptions of normality, the data will either be transformed or Friedman's test (i.e. non-parametric analogue to a repeated measures analysis of variance) will be used.

    Measured: Baseline to up to 30 days

  8. Changes in immunologic parameters

    Changes will be analyzed with descriptive statistics. Where there are sufficient data, repeated measures analysis of variance will be used to assess the effect of ibrutinib on these parameters across time. If the data do not meet the assumptions of normality, the data will either be transformed or Friedman's test (i.e. non-parametric analogue to a repeated measures analysis of variance) will be used.

    Measured: Baseline to up to 30 days

  9. Clinical benefit

    The proportion of patients achieving clinical benefit and their corresponding 95% CIs will be reported.

    Measured: Up to 30 days

  10. Objective response rate

    The proportion of patients achieving objective responses and their corresponding 95% confidence intervals (CIs) will be reported.

    Measured: Up to 30 days

  11. Pharmacokinetic (PK) parameters of ibrutinib in relation to ART-CYP3A4 interactions, including half-life (T1/2), oral clearance (CL/F), and area under the curve (AUC)

    Relevant individual PK parameters will be estimated using non-compartmental or compartmental PK methods. For each stratum, the PK variables will be tabulated and descriptive statistics (e.g., geometric means and coefficients of variation) calculated for each dose level. Pharmacokinetic parameters (i.e., T1/2, CL/F, and AUC) will be compared across relevant antiretroviral therapies using non-parametric statistical testing techniques.

    Measured: Course 1, day 8: pre-dose, 0.5, 1, 2, 4, 6, 8, and 24 hours

  12. Plasma concentrations of ibrutinib and its main metabolite

    Correlations with toxicity will be explored using non-parametric statistical testing techniques.

    Measured: Up to 30 days

  13. Time to tumor progression

    Time to tumor progression will be reported descriptively with medians and ranges.

    Measured: Up to 30 days

  14. Time to tumor response

    Time to tumor response will be reported descriptively with medians and ranges.

    Measured: From the first study treatment until documentation of first objective response, assessed up to 30 days

Timeline

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

  1. First posted9 Apr 2014 (estimated)
  2. Study startSep 2014
  3. Primary completionJul 2015
  4. Study completionJul 2015

Why it stopped: Inadequate accrual rate

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
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02109224
Sponsor's protocol ID
NCI-2014-00707
Other IDs
NCI-2014-00707, AMC-091, AMC-091, U01CA121947
Status last verified
Apr 2015
First submitted
7 Apr 2014
Last updated
20 Aug 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ibrutinib, Laboratory Biomarker Analysis and Pharmacological Study in people with Adult B Acute Lymphoblastic Leukemia and Chronic Lymphocytic Leukemia, run by National Cancer Institute (NCI) at 7 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 25 inclusion and 23 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: stopped early, as of the sponsor's last update on 20 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 was stopped early (reason given: Inadequate accrual rate). Results are not available in the source record.

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?

Incidence of toxicities assessed using National Cancer Institute (NCI) CTCAE version 4.0 (time frame: Up to 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 20 Aug 2015.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in