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Ann Arbor Stage II Grade 1 Contiguous Follicular LymphomaPhase 1NCT01829568

Rituximab, Lenalidomide, and Ibrutinib in Treating Patients With Previously Untreated Stage II-IV Follicular Lymphoma

A Phase 1 study testing Ibrutinib, Lenalidomide and Rituximab in people with Ann Arbor Stage II Grade 1 Contiguous Follicular Lymphoma and Ann Arbor Stage II Grade 1 Non-Contiguous Follicular Lymphoma, run by National Cancer Institute (NCI) at 7 sites in United States.

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 when given together with rituximab in treating patients with previously untreated stage II-IV follicular lymphoma. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ibrutinib, Lenalidomide and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
7 sitesUnited States
Study dates
26 Jun 2013to 6 Jun 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

  • Previously untreated, histologically confirmed follicular lymphoma, World Health Organization (WHO) classification grade I, II, or IIIa (> 15 centroblasts per high power field with centrocytes present) that is stage III, IV, or bulky (i.e., single mass >= 7 cm in any unidimensional measurement) stage II and requires therapy at the discretion of the primary physician
  • Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine needle aspirates are not acceptable for diagnosis
  • Failure to submit pathology specimens within 60 days of patient registration will be considered a major protocol violation
  • Institutional flow cytometry or immunohistochemistry must confirm cluster of differentiation 20 (CD20) antigen expression
  • All risk by follicular lymphoma international prognostic index (FLIPI): 0-5 risk factors
  • No prior systemic therapy for non-Hodgkin lymphoma (NHL) including chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy), radiation therapy, or radioimmunotherapy
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  • For non-NHL conditions, no chemotherapy, radiotherapy, or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of enrollment; no patients who have ongoing adverse events from agents administered more than 4 weeks previously
  • No prior exposure to any of the study agents
  • No corticosteroids within two weeks prior to study entry, except for maintenance therapy for a non-malignant disease; dose of corticosteroid or prednisone (or its equivalent) should not exceed 20 mg per day; corticosteroid premedication for rituximab is allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status must be =< 2
  • Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable; lesions that are considered non-measurable include the following:
  • Bone lesions (lesions if present should be noted)
  • Ascites
  • Pleural/pericardial effusion
  • Lymphangitis cutis/pulmonis
  • Bone marrow (involvement by NHL should be noted)
  • Patients with human immunodeficiency virus (HIV) infection are eligible, provided they meet the following:
  • No evidence of coinfection with hepatitis B or C
  • CD4+ cell count >= 400/mm^3
  • No evidence of resistant strains of HIV
  • If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV ribonucleic acid (RNA)/mL
  • If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL
  • No history of acquired immunodeficiency syndrome (AIDS)-defining conditions
  • No use of strong cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) inhibitors or inducers
  • No known central nervous system (CNS) involvement by lymphoma
  • No treatment with strong inhibitors or inducers of CYP3A4/5
  • No evidence of active hepatitis B or C infections (i.e., no positive serology for anti-hepatitis B virus [HBV] or anti-hepatitis C virus [HCV] antibodies); HBV seropositive patients (hepatitis B surface antigen [HBsAg] +) are eligible if they are closely monitored for evidence of active HBV infection by HBV deoxyribonucleic acid (DNA) testing and receive suppressive therapy with lamivudine or other HBV suppressive therapy until 6 months after the last rituximab dose
  • No history of erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome
  • No history of uncontrolled seizures
  • No autoimmune disorder that requires active immunosuppression
  • No intracranial hemorrhage within the last 6 months
  • Patients must be non-pregnant and non-nursing; 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 and again within 24 hours prior to 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; 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 sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy, or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure
  • No known human anti-chimeric antibody (HACA) positivity
  • No anticoagulation with warfarin is allowed; patients must not have received warfarin within 28 days prior to registration; alternative anticoagulant may be used
  • Patients must not be receiving concurrent treatment with other investigational drugs
  • Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide, ibrutinib, or other agents used in study
  • Patients must not have presence of transfusion-dependent thrombocytopenia
  • No currently active clinically significant cardiovascular disease including the following:
  • No uncontrolled arrhythmia
  • No congestive heart failure
  • No class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  • No history of myocardial infarction, deep venous or arterial thrombosis within 6 months prior to registration
  • No prior malignancy with the exceptions listed below:
  • Malignancy treated with curative intent and with no evidence of active disease for more than 3 years prior to screening and felt to be at low risk for recurrence by the 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
  • Patients must be >= 18 years of age
  • Absolute neutrophil count (ANC) >= 1,000/microliter (should be present independent of growth factor or transfusion support for at least 7 days prior to first dose of study drug)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) (should be present independent of growth factor or transfusion support for at least 7 days prior to first dose of study drug)
  • Total bilirubin =< 1.5 x ULN unless attributable to Gilbert's syndrome (should be present independent of growth factor or transfusion support for at least 7 days prior to first dose of study drug)
  • Creatinine clearance > 60 mL/min (patients on dialysis are not eligible); to be calculated by method of Cockcroft-Gault, using actual weight (should be present independent of growth factor or transfusion support for at least 7 days prior to first dose of study drug)
  • Creatinine =< 2 x ULN (should be present independent of growth factor or transfusion support for at least 7 days prior to first dose of study drug)
  • Platelet count >= 75,000/microliter (should be present independent of growth factor or transfusion support for at least 7 days prior to first dose of study drug)

Who cannot join

None listed.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Phase I Study of Rituximab, Lenalidomide, and Ibrutinib in Previously Untreated Follicular Lymphoma

This phase I trial studies the side effects and best dose of lenalidomide and ibrutinib when given together with rituximab in treating patients with previously untreated stage II-IV follicular lymphoma. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving lenalidomide and ibrutinib together with rituximab may work well in treating follicular lymphoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the recommended phase II doses of ibrutinib and lenalidomide for combination with rituximab in previously untreated follicular lymphoma.

SECONDARY OBJECTIVES:

  1. To determine pharmacokinetics of ibrutinib and its major metabolite (PCI-45227) when combined with lenalidomide and rituximab.

II. To determine the pharmacodynamics of basophil activation and Bruton tyrosine kinase (BTK) occupancy in peripheral blood mononuclear cells (PBMCs) over a 24-hour period of ibrutinib when given in combination with lenalidomide and rituximab.

OUTLINE: This is a dose-escalation study of lenalidomide and ibrutinib.

Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21 and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab intravenously (IV) on days 1, 8, 15, and 22 of cycle 1 and once weekly at weeks 13, 21, 29, and 37.

After completion of study treatment, patients are followed up every 4 months for 2 years and then every 6 months for 8 years or every 6 months or annually for 10 years.

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, CRA-032765, CRA032765

    Given PO

  • LenalidomideDrug

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

    Given PO

  • RituximabBiological

    Also called ABP 798, ABP-798, ABP798, BI 695500

    Given IV

Study groups in NCT01829568
Study groupRoleWhat they receive
Treatment (lenalidomide, ibrutinib, and rituximab)ExperimentalPatients receive lenalidomide PO QD on days 1-21 and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV on days 1, 8, 15, and 22 of cycle 1 and once weekly at weeks 13, 21, 29, and 37.
Receives: Drug: Ibrutinib; Drug: Lenalidomide; Biological: Rituximab

What is being measured

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

  1. Maximally tolerated dose (MTD) of lenalidomide and ibrutinib for combination with rituximab

    Defined as the highest dose at which 0 or 1 of 6 patients experience DLT. Will be determined by dose-limiting toxicities (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: 28 days

Secondary outcomes (5)

  1. Toxicities by attribute and grade

    Summarized for each dose level. Will be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

    Measured: Up to 10 years

  2. Complete response rate

    Estimated for each dose level.

    Measured: Up to 10 years

  3. Overall response rate

    Estimated for each dose level.

    Measured: Up to 10 years

  4. Progression-free survival (PFS)

    Estimated by Kaplan-Meier method for the whole number of patients in this study and at the MTD.

    Measured: The time between registration and disease progression or death, assessed up to 10 years

  5. Overall survival (OS)

    Estimated by Kaplan-Meier method for the whole number of patients in this study and at the MTD.

    Measured: The time between registration and death, assessed up to 10 years

Timeline

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

  1. First posted11 Apr 2013 (estimated)
  2. Study start26 Jun 2013
  3. Primary completion11 May 2015
  4. Study completion6 Jun 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
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01829568
Sponsor's protocol ID
NCI-2013-00792
Other IDs
NCI-2013-00792, CALGB-A051103, A051103, A051103, U10CA031946, U10CA180821
Status last verified
Jun 2026
First submitted
9 Apr 2013
Last updated
25 Jun 2026
Results posted
No
Data monitoring committee
No

Publications

  • Rutherford SC, Yin J, Pederson L, Perez Burbano G, LaPlant B, Shadman M, Li H, LeBlanc ML, Kenkre VP, Hong F, Blum KA, Dockter T, Martin P, Jung SH, Grant B, Rosenbaum C, Ujjani C, Barr PM, Unger JM, Cheson BD, Bartlett NL, Kahl B, Friedberg JW, Mandrekar SJ, Leonard JP. Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials. J Clin Oncol. 2023 Jan 10;41(2):336-342. doi: 10.1200/JCO.21.02301. Epub 2022 Jul 5.

    PubMed 35787017

  • Ujjani CS, Jung SH, Pitcher B, Martin P, Park SI, Blum KA, Smith SM, Czuczman M, Davids MS, Levine E, Lewis LD, Smith SE, Bartlett NL, Leonard JP, Cheson BD. Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103. Blood. 2016 Nov 24;128(21):2510-2516. doi: 10.1182/blood-2016-06-718106. Epub 2016 Oct 3.

    PubMed 27697771

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ibrutinib, Lenalidomide and Rituximab in people with Ann Arbor Stage II Grade 1 Contiguous Follicular Lymphoma and Ann Arbor Stage II Grade 1 Non-Contiguous Follicular Lymphoma, 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 53 inclusion and 0 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 25 Jun 2026. 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?

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?

Maximally tolerated dose (MTD) of lenalidomide and ibrutinib for combination with rituximab (time frame: 28 days). 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 NCT01829568, which also lists 2 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 25 Jun 2026.

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