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AzTrials

CCND1 PositivePhase 2NCT01880567

Ibrutinib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Older Patients With Newly Diagnosed Mantle Cell Lymphoma

A Phase 2 study testing Ibrutinib, Laboratory Biomarker Analysis and Rituximab in people with CCND1 Positive and CCND2 Positive, run by M.D. Anderson Cancer Center at 1 site 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 II trial studies how well ibrutinib and rituximab work in treating patients with mantle cell lymphoma that has come back or has not responded to treatment or older patients with newly diagnosed mantle cell lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
CCND1 Positive, CCND2 Positive, CCND3 Positive
What is being tested?
Ibrutinib, Laboratory Biomarker Analysis and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
113 participants
Where
1 siteUnited States
Study dates
15 Jul 2013to 31 Jul 2028
Phase
Phase 2
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

  • Relapsed/refractory MCL: Confirmed diagnosis of mantle cell lymphoma with cluster of differentiation (CD)20 and cyclin D1 through cyclin D3 positivity in tissue biopsy
  • Relapsed/refractory MCL: Patient has relapsed and or refractory MCL and must have received at least one prior treatment regimen for their disease; patient with leukemia phase (peripheral blood involvement), leptomeningeal disease, cerebral spinal fluid (CSF) MCL, central nervous system (CNS) MCL, non-measurable disease, gastrointestinal (GI) MCL, or bone marrow (BM) MCL are also eligible
  • Relapsed/refractory MCL: Understand and voluntarily sign an Institutional Review Board (IRB)-approved informed consent form
  • Relapsed/refractory MCL: Patients with bone marrow or gastrointestinal (GI) only involvement are acceptable
  • Relapsed/refractory MCL: Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
  • Relapsed/refractory MCL: Absolute neutrophil count (ANC) >= 500/mm^3; (patients who have bone marrow infiltration by MCL are eligible if their ANC is >= 500/mm^3 [growth factor allowed]; these patients should be discussed with either the principal investigator [PI] or Co-PI of the study for final approval)
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  • Relapsed/refractory MCL: Platelet count >= 30,000/mm^3 (transfusion to reach platelet count allowed); (patients who have bone marrow infiltration by MCL are eligible if their platelet level is equal to or > than 15,000/mm^3; these patients should be discussed with either the PI or Co-PI of the study for final approval)
  • Relapsed/refractory MCL: Aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2 x upper limit of normal or < 5 x upper limit of normal if hepatic metastases are present
  • Relapsed/refractory MCL: Serum bilirubin < 1.5 mg/dl
  • Relapsed/refractory MCL: Creatinine (Cr) clearance >= 30 mL/min
  • Relapsed/refractory MCL: Patients must be willing to receive transfusions of blood products
  • Relapsed/refractory MCL: Willing and able to participate in all study related procedures and therapy including swallowing capsules without difficulty
  • Newly diagnosed MCL: Confirmed diagnosis of MCL with CD20 and cyclin D1 positivity in tissue biopsy; patients must have never received any prior therapy for their disease
  • Newly diagnosed MCL: Understand and voluntarily sign an IRB-approved informed consent form
  • Newly diagnosed MCL: Age > 65 years at the time of signing the informed consent
  • Newly diagnosed MCL: Patients should in general have bi-dimensional measurable disease with their biggest tumor less than 10 cm; (bone marrow or gastrointestinal [GI] only involvement is acceptable)
  • Newly diagnosed MCL: Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
  • Newly diagnosed MCL: Absolute neutrophil count (ANC) > 750/mm^3; patients who have bone marrow infiltration by MCL are eligible if their ANC is equal to or > than 500
  • Newly diagnosed MCL: Platelet count > 50,000/mm^3; patients who have bone marrow infiltration by MCL are eligible if their platelet level is equal to or > than 15,000 /mm^3; (platelet transfusions are allowed; these patients should be discussed with either the PI or Co-PI of the study for final approval)
  • Newly diagnosed MCL: AST (SGOT) and ALT (SGPT) < 2 x upper limit of normal or < 5 x upper limit of normal if hepatic metastases are present
  • Newly diagnosed MCL: Uric acid within normal limits (allopurinol is allowed to bring abnormal level to within normal limits)
  • Newly diagnosed MCL: Serum bilirubin < 1.5 mg/dl
  • Newly diagnosed MCL: Creatinine (Cr) Clearance >= 30 mL/min
  • Newly diagnosed MCL: Ki67 protein (Ki67) < 50%
  • Newly diagnosed MCL: Disease free of prior malignancies of equal to or greater than 6 months with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated, with a life expectancy > 3 years
  • Newly diagnosed MCL: Patients must be willing to receive transfusions of blood products
  • Newly diagnosed MCL: Willing and able to participate in all study related procedures and therapy including swallowing capsules without difficulty

Who cannot join

  • Relapsed/refractory MCL: Any serious medical condition that places the patient at unacceptable risk and/or would prevent the subject from signing the informed consent form; examples include but are not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, active infection, active hemorrhage, or psychiatric illness
  • Relapsed/refractory MCL: Pregnant or breast feeding females
  • Relapsed/refractory MCL: Known human immunodeficiency virus (HIV) infection; patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum hepatitis B antibody); known hepatitis C infection is allowed as long as there is no active disease and is cleared by gastrointestinal (GI) consultation
  • Relapsed/refractory MCL: The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient's health and survival, than of the MCL, within the subsequent 6 months at the time of consent
  • Relapsed/refractory MCL: History of stroke or intracranial hemorrhage within 6 months prior to signing the consent
  • Relapsed/refractory MCL: Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months at the time of consent or any class 3 (moderate) or 4 (severe) cardiac disease defined by the New York Heart Association classification
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  • Relapsed/refractory MCL: Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, bradycardia (< 50 beats per minute [bpm]), or corrected QT (QTc) > 500 msec
  • Relapsed/refractory MCL: Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
  • Relapsed/refractory MCL: Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, major surgery within 4 weeks or vaccination with live attenuated vaccines within 4 weeks of the first dose of study drug
  • Relapsed/refractory MCL: Prior treatment with ibrutinib
  • Relapsed/refractory MCL: Requires anticoagulation with warfarin or equivalent vitamin K antagonist
  • Relapsed/refractory MCL: Requires treatment with strong cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) inhibitors
  • Newly Diagnosed MCL: Any serious medical condition that places the patient at unacceptable risk and/or would prevent the subject from signing the informed consent form; examples include but are not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, active infection requiring treatment with systemic antibiotics, antiviral or antifungal agents, active hemorrhage, or psychiatric illness
  • Newly diagnosed MCL: Known HIV infection; patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody); known hepatitis C infection is allowed as long as there is no active disease and is cleared by GI consultation
  • Newly diagnosed MCL: The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient's health and survival, than of the MCL, within the subsequent 6 months at the time of consent
  • Newly diagnosed MCL: History of stroke or intracranial hemorrhage within 6 months prior to signing the consent
  • Newly diagnosed MCL: Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months at the time of consent or any class 3 (moderate) or 4 (severe) cardiac disease defined by the New York Heart Association Classification
  • Newly diagnosed MCL: Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia (< 50 bpm), or QTc > 500 msec
  • Newly diagnosed MCL: Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
  • Newly diagnosed MCL: Major surgery within 4 weeks or vaccination with live attenuated vaccines within 4 weeks of the first dose of study drug
  • Newly diagnosed MCL: Prior treatment with ibrutinib
  • Newly diagnosed MCL: Requires concomitant anticoagulation with warfarin or equivalent vitamin K antagonist
  • Newly diagnosed MCL: Requires treatment with strong CYP3A4/5 inhibitors
  • Newly diagnosed MCL: Patients with blastoid and pleomorphic variants
  • Newly diagnosed MCL: Ki-67 to be equal or more than 50%
  • Newly diagnosed MCL: Central nervous system lymphoma
  • Newly diagnosed MCL: Patients with bi-dimensional measurable disease with a tumor >= 10 cm

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: A Phase II Study of Ibrutinib Plus Rituximab in Patients With Relapsed/Refractory Mantle Cell Lymphoma or Elderly Patients With Newly Diagnosed MCL

This phase II trial studies how well ibrutinib and rituximab work in treating patients with mantle cell lymphoma that has come back or has not responded to treatment or older patients with newly diagnosed mantle cell 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 find cancer cells and help kill them. Giving ibrutinib and rituximab may be an effective treatment for mantle cell lymphoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the response rate of ibrutinib plus rituximab in patients with relapsed and/or refractory mantle cell lymphoma (MCL).

II. To evaluate the safety and response rate of ibrutinib plus rituximab in elderly patients (> 65) with newly-diagnosed, untreated MCL.

SECONDARY OBJECTIVES:

  1. To further evaluate the toxicity profile of the combination of ibrutinib and rituximab in patients with relapsed and/or refractory MCL.

II. To estimate the overall response rate (ORR); (partial response [PR] or better), the response duration (DOR), progression-free survival (PFS), time to progression (TTP) and overall survival (OS) in patients with relapsed and/or refractory MCL; clinical benefit response (CBR) = (minimal response [MR] + ORR) will also be evaluated.

III. To estimate the response duration, PFS, time to progression (TTP), and OS in elderly patients (> 65) with newly-diagnosed, untreated MCL.

EXPLORATORY OBJECTIVES:

  1. To correlate detected gene mutations and changes in gene and/or protein expression with response to treatment.

OUTLINE:

Patients receive ibrutinib orally (PO) daily on days 1-28 and rituximab intravenously (IV) over 4-8 hours on days 1, 8, 15, and 22 of course 1; on day 1 of courses 3-8; and on day 1 of every other course for all subsequent courses. Treatment with rituximab repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Courses with ibrutinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.

Being tested
Ibrutinib, Laboratory Biomarker Analysis, Rituximab
Medical subject headings
Lymphoma, Mantle-Cell

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

  • RituximabBiological

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

    Given IV

Study groups in NCT01880567
Study groupRoleWhat they receive
Treatment (ibrutinib, rituximab)ExperimentalPatients receive ibrutinib PO daily on days 1-28 and rituximab IV over 4-8 hours on days 1, 8, 15, and 22 of course 1; on day 1 of courses 3-8; and on day 1 of every other course for all subsequent courses. Treatment with rituximab repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Courses with ibrutinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Biological: Rituximab

What is being measured

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

  1. Overall response (complete response and partial response), assessed by the International Workshop Standardized Response Criteria for non-Hodgkin lymphoma

    Overall response will be monitored using the Bayesian stopping boundaries calculated based on beta-binomial distribution.

    Measured: Up to 8 weeks

  2. Overall response (complete response and partial response) in elderly patients with newly-diagnosed, untreated mantle cell lymphoma, assessed by the International Workshop Standardized Response Criteria for non-Hodgkin lymphoma

    Overall response will be monitored using the Bayesian stopping boundaries calculated based on beta-binomial distribution.

    Measured: Up to 8 weeks

  3. Incidence of toxicity, defined as grade 3 or higher non-hematologic toxicity, grade 3 neutropenia, grade 4 hematologic toxicity, inability to administer full schedule and dose, or inability to receive treatment day 1 of course 2

    Toxicity data will be summarized by frequency tables for all patients.

    Measured: Up to 4 weeks

  4. Incidence of grade 3 or higher non-hematologic toxicity, grade 3 neutropenia, grade 4 hematologic toxicity, inability to administer full schedule and dose, or inability to receive treatment day 1 of course 2 in newly diagnosed elderly patients

    Toxicity data will be summarized by frequency tables for all patients.

    Measured: Up to 4 weeks

Secondary outcomes (9)

  1. Clinical benefit response (minimal response + overall response rate),

    Will be assessed by the International Workshop Standardized Response Criteria for non-Hodgkin lymphoma.

    Measured: Up to 6 years

  2. Duration of response

    Duration of response will be estimated using the method of Kaplan and Meier. Comparison by important subgroups will be made using the log-rank test. Cox proportional hazards will be employed for multivariate analysis.

    Measured: Up to 6 years

  3. Progression-free survival

    Progression-free survival will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-events outcomes.

    Measured: Up to 6 years

  4. Time to progression

    Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-events outcomes.

    Measured: Up to 6 years

  5. Overall survival

    Overall survival will be estimated using the method of Kaplan and Meier. Comparison by important subgroups will be made using the log-rank test. Cox proportional hazards will be employed for multivariate analysis.

    Measured: Up to 6 years

  6. Duration of response in elderly patients with newly diagnosed, untreated mantle cell lymphoma

    Intend-to-treat analysis will be applied to the eligible patients.

    Measured: Up to 6 years

  7. Progression-free survival in elderly patients with newly diagnosed, untreated mantle cell lymphoma

    Intend-to-treat analysis will be applied to the eligible patients.

    Measured: Up to 6 years

  8. Overall survival in elderly patients with newly diagnosed, untreated mantle cell lymphoma

    Overall response will be monitored using the Bayesian stopping boundaries calculated based on beta-binomial distribution.

    Measured: Up to 6 years

  9. Time to progression in elderly patients with newly diagnosed, untreated mantle cell lymphoma

    Measured: Up to 6 years

Timeline

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

  1. First posted19 Jun 2013 (estimated)
  2. Study start15 Jul 2013
  3. Primary completion31 Jul 2028 (estimated)
  4. Study completion31 Jul 2028 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
113 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01880567
Sponsor's protocol ID
2013-0090
Other IDs
NCI-2013-01304, 2013-0090
Status last verified
Jul 2026
First submitted
14 Jun 2013
Last updated
8 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Jain P, Zhao S, Lee HJ, Hill HA, Ok CY, Kanagal-Shamanna R, Hagemeister FB, Fowler N, Fayad L, Yao Y, Liu Y, Moghrabi OB, Navsaria L, Feng L, Nogueras Gonzalez GM, Xu G, Thirumurthi S, Santos D, Iliescu C, Tang G, Medeiros LJ, Vega F, Avellaneda M, Badillo M, Flowers CR, Wang L, Wang ML. Ibrutinib With Rituximab in First-Line Treatment of Older Patients With Mantle Cell Lymphoma. J Clin Oncol. 2022 Jan 10;40(2):202-212. doi: 10.1200/JCO.21.01797. Epub 2021 Nov 19.

    PubMed 34797699

  • Wang ML, Lee H, Chuang H, Wagner-Bartak N, Hagemeister F, Westin J, Fayad L, Samaniego F, Turturro F, Oki Y, Chen W, Badillo M, Nomie K, DeLa Rosa M, Zhao D, Lam L, Addison A, Zhang H, Young KH, Li S, Santos D, Medeiros LJ, Champlin R, Romaguera J, Zhang L. Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial. Lancet Oncol. 2016 Jan;17(1):48-56. doi: 10.1016/S1470-2045(15)00438-6. Epub 2015 Nov 28.

    PubMed 26640039

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib, Laboratory Biomarker Analysis and Rituximab in people with CCND1 Positive and CCND2 Positive, 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 27 inclusion and 27 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 8 Jul 2026. 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?

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?

Overall response (complete response and partial response), assessed by the International Workshop Standardized Response Criteria for non-Hodgkin lymphoma (time frame: Up to 8 weeks). The study lists 4 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 NCT01880567, 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 8 Jul 2026.

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