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Ann Arbor Stage II Follicular LymphomaPhase 2NCT02532257

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

A Phase 2 study testing Ibrutinib, Laboratory Biomarker Analysis and Lenalidomide in people with Ann Arbor Stage II Follicular Lymphoma and Ann Arbor Stage II Marginal Zone Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies how well ibrutinib in combination with rituximab and lenalidomide works in treating patients with previously untreated, stage II-IV follicular lymphoma or marginal zone lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ibrutinib, Laboratory Biomarker Analysis and Lenalidomide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteUnited States
Study dates
11 Apr 2016to 15 Aug 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 CD20+ follicular lymphoma, grade 1, 2, or 3a or marginal zone lymphoma
  • Have had no prior systemic treatment for lymphoma
  • Bi-dimensionally measurable disease, with at least one mass lesion >= 2 cm in longest diameter by computed tomography (CT), positron emission tomography (PET)/CT, and/or magnetic resonance imaging (MRI)
  • In the opinion of the investigator would benefit from systemic therapy
  • Stage II, III, or IV disease
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
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  • Absolute neutrophil count (ANC) >= 1,000/mm^3, independent of growth factor support (within 28 days prior to signing informed consent).
  • Platelet counts >= 100,000/mm^3 or >= 50,000/mm^3 if bone marrow involvement with lymphoma, independent of transfusion support in either situation (within 28 days prior to signing informed consent).
  • Serum aspartate transaminase (AST) or alanine transaminase (ALT) < 3 x upper limit of normal (ULN)
  • Creatinine clearance > 30 ml/min calculated by modified Cockcroft-Gault formula
  • Bilirubin < 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3 g/dL
  • Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN
  • Must be able to adhere to the study visit schedule and other protocol requirements
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study; females of childbearing potential: must either completely abstain from heterosexual sexual conduct or must use 2 methods of reliable contraception, 1 highly effective (intrauterine device, birth control pills, hormonal patches, injections, vaginal rings, or implants) and at least 1 additional method (condom, diaphragm, cervical cap) of birth control; reliable contraceptive methods must be started at least 4 weeks before lenalidomide; males who are sexually active must be practicing complete abstinence or agree to a condom during sexual contact with a pregnant female or female of child bearing potential; men must agree to not donate sperm during and after the study; for females, these restrictions apply at least 4 weeks before study treatment, during the period of therapy and for 1 month after the last dose of study drug; for males, these restrictions apply during the period of therapy and for 3 months after the last dose of study drug
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [Beta-hCG]) pregnancy test at screening; women who are pregnant or breastfeeding are ineligible for this study; females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program
  • Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
  • All study participants must be registered into the mandatory Revlimid REMS program, and be willing and able to comply with the requirements of the REMS program

Who cannot join

  • Known central nervous system lymphoma or leptomeningeal disease, except subjects with a history of central nervous system lymphoma treated and in remission > 6 months
  • Evidence of diffuse large B-cell transformation
  • Grade 3b FL
  • Any prior history of other malignancy besides FL or marginal zone lymphoma, unless the patient has been free of disease for >= 5 years and felt to be at low risk for recurrence by the treating physician, except:
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated cervical carcinoma in situ without evidence of disease
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  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk, including but not limited to:
  • Moderate to severe hepatic impairment (Child-Pugh classes B and C)
  • Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B virus infection, or any uncontrolled active systemic infection
  • Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated
  • Prior use of ibrutinib or other BTK inhibitors, rituximab or lenalidomide
  • Concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc., or chronic administration glucocorticoid equivalent of > 10 mg/day of prednisone) within 28 days of the first dose of study drug
  • Known anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon); if patients have been on warfarin or equivalent vitamin K antagonists in the past, they will not be eligible if administered within 30 days of the first dose of study drug
  • Requires chronic treatment with strong CYP3A inhibitors; if patients have been on a strong CYP3A inhibitor in the past, they will not be eligible if the CYP3A inhibitor was administered within 7 days of the first dose of study drug
  • Requires chronic treatment with strong CYP3A inducers, for a list of strong CYP3A inducers, see the protocol. If patients have been on a strong CYP3A inducer in the past, they will not be eligible if the CYP3A inducer was administered within 7 days of the first dose of study drug
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional classification
  • Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block
  • Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia
  • History of stroke or intracranial hemorrhage within 6 months prior to study entry
  • Vaccinated with live, attenuated vaccines within 4 weeks of study entry
  • Lactating or pregnant subjects
  • Administration of any investigational agent within 28 days of first dose of study drug
  • Patients who have undergone major surgery within 7 days or minor surgery within 3 days of first dose of study drug

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: An Open Label, Phase 2 Study of Ibrutinib in Combination With Rituximab and Lenalidomide in Previously Untreated Subjects With Follicular Lymphoma and Marginal Zone Lymphoma

This phase II trial studies how well ibrutinib in combination with rituximab and lenalidomide works in treating patients with previously untreated, stage II-IV follicular lymphoma or marginal zone lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Giving ibrutinib in combination with rituximab and lenalidomide may work better in treating follicular lymphoma or marginal zone lymphoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in patients with previously untreated follicular lymphoma (FL) and marginal zone lymphoma (determined by progression-free survival at 2 years).

SECONDARY OBJECTIVES:

  1. To evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in subjects with FL as assessed by complete response rate (CR) at 120 weeks, overall response rate (ORR), duration of response (DOR), event free survival (EFS), time to next anti-lymphoma treatment (TTNT), and overall survival (OS).

II. To evaluate the safety and tolerability of ibrutinib combined with rituximab and lenalidomide in previously untreated subjects with FL and marginal zone lymphoma.

EXPLORATORY OBJECTIVES:

  1. To evaluate prognostic and mechanistic biomarkers relative to treatment outcomes.

OUTLINE:

Patients receive lenalidomide orally (PO) on days 1-21, rituximab intravenously (IV) over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 1 year and then every 24 weeks for 2 years.

Being tested
Ibrutinib, Laboratory Biomarker Analysis, Lenalidomide, Rituximab
Medical subject headings
Lymphoma, Follicular

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, Imbruvica, PCI-32765

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LenalidomideDrug

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

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

Study groups in NCT02532257
Study groupRoleWhat they receive
Treatment (lenalidomide, rituximab, ibrutinib)ExperimentalPatients receive lenalidomide PO on days 1-21, rituximab IV over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Biological: Rituximab

What is being measured

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

  1. Progression Free Survival (PFS)

    Evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in patients with previously untreated FL and marginal zone lymphoma (determined by PFS at 2 years). Response will be assessed by the investigator based on the 2014 Cheson Lugano criteria. The 2-year PFS rate will be calculated and corresponding 95% confidence interval (CI) will be derived. Kaplan-Meier method will be used to estimate the PFS. Corresponding 95% CI will be summarized. Cox proportional hazards models will be used to assess the effects of patient prognostic factors on time-to-event endpoints.

    Measured: 24 months

Secondary outcomes (6)

  1. Complete Response (CR) Rate

    Will be defined as the percentage of participants with a CR at 120 weeks as determined by the principal investigator (Cheson, Lugano classification 2014).

    Measured: At 120 weeks

  2. Overall Response Rate (ORR) (CR Rate + Partial Response [PR])

    Will be defined as the percentage of participants with an ORR and assessed by the investigator based on Cheson, Lugano 2014. The best ORR will be recorded.

    Measured: Up to 3 years

  3. Duration of Response (DOR)

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

    Measured: Time by which measurement criteria for CR rate or PR, whichever is recorded first, is met until death or the first date by which progressive disease is documented; assessed up to 71.2 months

  4. Event Free Survival (EFS)

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

    Measured: From the date of course 1, day 1 to the date of first documented progression, transformation to diffuse large B-cell lymphoma, initiation of new anti-lymphoma treatment, or death; assessed up to 70.2 months

  5. Time to Next Anti-lymphoma Treatment (TTNT)

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

    Measured: From the date of course 1, day 1 to the date of first documented administration of any anti-lymphoma treatment (chemotherapy, radiotherapy, immune therapy, radioimmunotherapy, or other experimental therapy); assessed up to 75.8 months

  6. Overall Survival (OS) Rate

    Secondary endpoints included best and 120 week complete response rate (CRR) and ORR by Lugano classification, duration of response, event free survival, time to next anti-lymphoma treatment, overall survival (OS) and safety. Response evaluation was performed at cycle 4, day 1, cycle 7 day 1, at the end of cycle 12, then every 12 weeks for the first four assessments, then every 24 weeks until disease progression

    Measured: From the date of course 1, day 1 to the date of death regardless of cause; assessed up to 78 months

Timeline

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

  1. First posted25 Aug 2015 (estimated)
  2. Study start11 Apr 2016
  3. Primary completion15 Aug 2023
  4. Study completion15 Aug 2023

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02532257
Sponsor's protocol ID
2015-0361
Other IDs
NCI-2015-01513, 2015-0361
Status last verified
Sep 2024
First submitted
21 Aug 2015
Last updated
24 Sep 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Gordon MJ, Feng L, Strati P, Lee HJ, Hagemeister FB, Westin JR, Samaniego F, Marques-Piubelli ML, Vega Vazquez F, Parra Cuentas ER, Solis-Soto LM, Ma W, Wang J, Claret L, Averill B, Ibanez K, Fayad LE, Flowers CR, Green MR, Davis RE, Neelapu SS, Fowler NH, Nastoupil LJ. Safety and efficacy of ibrutinib in combination with rituximab and lenalidomide in previously untreated follicular and marginal zone lymphoma: An open label, phase 2 study. Cancer. 2024 Mar 15;130(6):876-885. doi: 10.1002/cncr.35114. Epub 2023 Nov 20.

    PubMed 37985359

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib, Laboratory Biomarker Analysis and Lenalidomide in people with Ann Arbor Stage II Follicular Lymphoma and Ann Arbor Stage II Marginal Zone Lymphoma, run by M.D. Anderson Cancer Center at 1 site 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 17 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 24 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Progression Free Survival (PFS) (time frame: 24 months). 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 NCT02532257, which also lists 1 linked publication.

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 24 Sep 2024.

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