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Recurrent Diffuse Large B-Cell LymphomaPhase 1NCT01955499

Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

A Phase 1 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Follicular Lymphoma, run by National Cancer Institute (NCI) at 3 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of lenalidomide and ibrutinib in treating patients with B-cell non-Hodgkin lymphoma that has returned (relapsed) or not responded to treatment (refractory). Lenalidomide helps shrink or slow the growth of non-Hodgkin lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
3 sitesin 2 countries
Study dates
24 Sep 2013to 6 May 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Histologically confirmed B-cell non-Hodgkin's lymphoma (NHL) of any of the following subtypes recognized by the World Health Organization (WHO) classification: diffuse large B-cell lymphoma, mantle cell lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, or follicular lymphoma; patients with evidence of histological transformation to diffuse large B-cell lymphoma from indolent NHL are eligible
  • Patients must have received at least one prior therapy; prior autologous stem cell transplant is permitted; patients with diffuse large B-cell lymphoma who have not received high-dose therapy (HDT)/autologous stem cell transplant (ASCT) must be ineligible for HDT/ASCT; prior allogeneic stem cell transplant is not permitted; prior ibrutinib is not permitted
  • Age >= 18 years. Because no dosing or adverse event data are currently available on the use of ibrutinib in combination with lenalidomide in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
  • Patients must have normal organ and marrow function, independent of growth factor or transfusion support; patients should not receive growth factors or transfusions for at least 7 days prior to first dose of study drug, with the exception of pegylated G-CSF (pegfilgrastim) and darbepoeitin which require at least 14 days prior to screening and randomization
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  • Absolute neutrophil count >= 1,000/mcL in the absence of growth factor administration
  • Platelets >= 50,000/mcL in the absence of transfusion support within 7 days prior to determination of eligibility
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilberts disease
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal unless due to disease
  • Creatinine =< 2.0 mg/dL OR creatinine clearance >= 50 mL/min as determined by the Cockcroft-Gault equation or a 24 hour urine collection
  • Non-pregnant and non-nursing; due to the known teratogenic potential of lenalidomide and the unknown teratogenic potential of ibrutinib, pregnant or nursing patients may not be enrolled; females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to and again within 24 hours of starting cycle 1 of lenalidomide; further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide and for 28 days after the last dose of study drug; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; a FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure
  • Patients with human immunodeficiency virus (HIV) infection are eligible provided they meet the following criteria: no evidence of co-infection with hepatitis B or C, cluster of differentiation (CD)4 count >= 400 cells/mm^3, no resistant viral strains, on highly active antiretroviral treatment (HAART) therapy with a viral load < 50 RNA copies/ml, and no history of acquired immunodeficiency syndrome (AIDS)-defining conditions
  • Ability to understand and the willingness to sign a written informed consent document
  • Curative therapy must have been exhausted or not feasible to administer; patients with diffuse large B-cell lymphoma, germinal center subtype should only enroll on the study if there are no other potentially effective therapeutic options

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; steroids used for disease related symptoms should be stopped within 48 hours of protocol therapy; patients who have had prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor; patients who received monoclonal antibody =< 6 weeks prior to first administration of study treatment
  • Patients who are receiving any other investigational agents
  • Patients with active central nervous system (CNS) involvement with lymphoma should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to lenalidomide or compounds of similar chemical or biologic composition to lenalidomide including thalidomide
  • Patients receiving any medications or substances that are strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians' Desk Reference may also provide this information; 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 medicine or herbal product
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements; currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction, unstable angina or acute coronary syndrome within 6 months prior to randomization
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  • Recent infections requiring systemic treatment need to have completed therapy > 14 days before the first dose of study drug
  • Medications with a risk of causing Torsades de Pointes are not permitted; although concomitant treatment with corrected QT (QTc) prolonging agents is not strictly prohibited, these agents should be avoided whenever possible and an alternative non-QTc prolonging drug should be substituted if possible
  • Patients requiring any therapeutic anticoagulation are excluded; patients who have received warfarin or other vitamin K antagonists within 28 days or are taking warfarin or other vitamin K antagonists are not eligible
  • Patients who are within 4 weeks of major surgery or within 2 weeks of minor surgery
  • Concurrent systemic immunosuppressant therapy other than corticosteroids (e.g. cyclosporine A, tacrolimus, etc) within 28 days of the first dose of study drug
  • Vaccinated with live attenuated vaccines within 4 weeks of first dose of study drug
  • Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 5), grade =< 1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia
  • Known bleeding disorders (e.g. von Willebrand's disease) or hemophilia
  • Unwilling or unable to participate in all required study evaluations and procedures
  • Currently active, clinically significant hepatic impairment (>= moderate hepatic impairment according to the National Cancer Institute (NCI)/Child Pugh classification
  • Patients requiring daily corticosteroids at a prednisone equivalent of >= 20 mg daily should not be enrolled; if corticosteroids can be discontinued (or reduced to < 20 mg per day of prednisone or equivalent), the discontinuation or dose reduction should be done at least 7 days prior to first dose
  • Unable to swallow capsules, or disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, or symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
  • Serologic status reflecting active hepatitis B or C infection; patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAG), or hepatitis C antibody, must have a negative polymerase chain reaction (PCR) prior to enrollment; (PCR positive patients will be excluded)

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

Canada1 site

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase I Study of Ibrutinib (PCI-32765) in Combination With Lenalidomide in Relapsed and Refractory B-Cell Non-Hodgkin's Lymphoma

This phase I trial studies the side effects and best dose of lenalidomide and ibrutinib in treating patients with B-cell non-Hodgkin lymphoma that has returned (relapsed) or not responded to treatment (refractory). Lenalidomide helps shrink or slow the growth of non-Hodgkin lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide with ibrutinib may work better in treating non-Hodgkin lymphoma than giving either drug alone.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination of lenalidomide and ibrutinib in patients with relapsed and refractory B-cell non-Hodgkin's lymphoma (NHL).

II. To define the qualitative and quantitative toxicities of the combination of lenalidomide and ibrutinib.

SECONDARY OBJECTIVES:

  1. To describe the overall objective response rate to the combination of lenalidomide and ibrutinib in patients with relapsed or refractory B-cell NHL.

II. To describe the response duration and two-year progression free survival (PFS) in patients with B-cell NHL receiving lenalidomide and ibrutinib.

III. To characterize the pharmacokinetics of the combination of lenalidomide and ibrutinib in patients with relapsed or refractory B-cell NHL.

IV. To identify associations of genetic polymorphisms in drug metabolizing enzymes, transporters or target genes with pharmacokinetics, pharmacodynamics, and clinical outcomes.

  1. To monitor the effects of combined therapy with ibrutinib and lenalidomide on B- T-, and natural killer (NK)-cell subsets by flow cytometry and quantitative immunoglobulin levels.

VI. To explore the effects of the combination of ibrutinib and lenalidomide on pharmacodynamic markers including T helper cell, type 1 (TH1) and T helper cell, type 2 (TH2) cytokines, ex vivo NK cell cytotoxicity, serum micro ribonucleic acids (RNAs), plasma metabolites, and levels of Bruton's tyrosine kinase occupancy and other selected kinases.

VII. To explore the relationship between pretreatment pathologic prognostic features and overall objective response.

OUTLINE: This is a dose-escalation study.

Patients receive lenalidomide orally (PO) on days 1-21 and ibrutinib PO on days 1-28 (days 2-28 of cycle 1). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT or PET/CT throughout the study. Patients may undergo bone marrow biopsy and aspiration and MRI as clinically indicated.

After completion of study treatment, patients are followed up for 4 weeks and then every 6 months thereafter.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Ibrutinib
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Mantle-Cell

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT and/or PET/CT

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765

    Given PO

  • LenalidomideDrug

    Also called CC 5013, CC-5013, CC5013, CDC 501

    Given PO

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

Study groups in NCT01955499
Study groupRoleWhat they receive
Treatment (lenalidomide, ibrutinib)ExperimentalPatients receive lenalidomide PO on days 1-21 and ibrutinib PO on days 1-28 (days 2-28 of cycle 1). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and CT or PET/CT throughout the study. Patients may undergo bone marrow biopsy and aspiration and MRI as clinically indicated.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Ibrutinib; Drug: Lenalidomide; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

What is being measured

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

  1. Maximum tolerated dose (MTD)

    Defined as the highest safely tolerated dose where at most one patient experiences dose limiting toxicity (DLT) with the next higher dose having at least 2 patients who experience DLT.

    Measured: 28 days

  2. Incidence of toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 criteria

    Worst grade toxicities will be recorded for each patient and summarized using frequency tables. Tolerability of the regimen is assessed by summarizing the number of patients who required dose modifications and/or dose delays. In addition, the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial will be counted.

    Measured: Up to 2 years

Secondary outcomes (5)

  1. Number of patients responding to treatment

    Responses will be summarized with simple descriptive statistics, delineating complete responses from lesser responses and stable disease or progressive disease according to the International Harmonization Project Lymphoma Response Criteria and the Response Criteria for Waldenstrom's Macroglobulinemia.

    Measured: Up to 2 years

  2. Degree of response

    Responses will be summarized with simple descriptive statistics, delineating complete responses from lesser responses and stable disease or progressive disease according to the International Harmonization Project Lymphoma Response Criteria and the Response Criteria for Waldenstrom's Macroglobulinemia.

    Measured: Up to 2 years

  3. Duration of overall response

    Summarized with simple descriptive statistics.

    Measured: From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years

  4. Duration of stable disease

    Summarized with simple descriptive statistics.

    Measured: From the start of the treatment until the criteria for progression are met, assessed up to 2 years

  5. Progression free survival (PFS)

    Summarized with simple descriptive statistics.

    Measured: Duration of time from the start of treatment to the time of measured progression or death, assessed up to 2 years

Timeline

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

  1. First posted7 Oct 2013 (estimated)
  2. Study start24 Sep 2013
  3. Primary completion6 Nov 2024
  4. Study completion6 May 2027 (estimated)

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
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01955499
Sponsor's protocol ID
NCI-2013-01810
Other IDs
NCI-2013-01810, OSU 13022, 9426, 9426, K24CA201524, P30CA016058, U01CA076576, U01CA132123
Status last verified
May 2026
First submitted
27 Sep 2013
Last updated
13 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Follicular Lymphoma, run by National Cancer Institute (NCI) at 3 sites in 2 countries.

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 15 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, Canada. 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?

This study is still under way. Results are not available in the source record yet.

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?

Maximum tolerated dose (MTD) (time frame: 28 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?

On the ClinicalTrials.gov record for NCT01955499.

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 13 May 2026.

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