Dose Finding Study of Ibrutinib Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma

March 20, 2026 updated by: Hackensack Meridian Health

Phase Ib Dose Finding Study of Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765) Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma (MCL)

This is a dose-escalation to determine the MTD and/or RPII for combinations of ibrutinib (PCI-32765) plus lenalidomide/rituximab in patients with relapsed/refractory mantle cell lymphoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Mantle cell lymphoma (MCL) is a relatively rare subtype (3% to 6% (Zhou, 2008) of mature B cell non-Hodgkin lymphomas (NHL), with a median age at diagnosis in mid to late 60's, a male predominance (3/1) and typically advanced stage presentation though only about 1/3 of patients are truly symptomatic at baseline (Armitage, 1998). Although significant controversies remain in the management of MCL, all would agree that the challenges associated with MCL, particularly the poor results with standard chemotherapy and frequent chemoresistance have pushed the community to be more innovative and active in clinical research. Hence the median OS has clearly improved over the last 3 decades (from 2-3y to >5y) (Goy, 2011a), thanks to deeper responses obtained with intensive regimens in younger patients (an early CR translates into clearly better outcome) and also better salvage therapies with now MCL being the only lymphoma with 4 new biologicals approved (3 in the US and 1 in EU).

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • The Cancer Center at Hackensack University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age greater than or equal to 18 years.
  • Histologically or cytologically confirmed diagnosis of MCL.
  • Relapsed or refractory MCL patients who have received at least one prior therapy are eligible. Patients who have previously received high-dose chemotherapy with peripheral stem cell support are eligible.
  • Presence of at least one lymph node evaluable or mass measurable for response.
  • Eastern Cooperative Oncology Group Performance Status greater than 2.
  • Platelets > 75,000/μL and absolute neutrophils count (ANC) > 1,000/μL within 14 days of study registration (unless the treating physician deems the neutropenia is related to bone marrow involvement, then an ANC of > 750/mm 3 is allowed)
  • Normal renal function defined as serum creatinine less than 2.
  • Recovery from any previous treatment therapy.
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test
  • 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.
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
  • Ability to understand, and willingness to sign, a written informed consent document.
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anti-coagulation (patients intolerant to ASA may use low molecular weight heparin).
  • Normal organ and bone marrow function parameter:

Laboratory tests Required value WBC >3000/μL* Absolute neutrophils count >1,000/μL* Platelets >75,000/μL Total bilirubin < 1.5Within normal institutional limits AST (SGOT) and ALT (SGPT) <3 x institutional upper limit of normal Creatinine or creatinine clearance <1.5 within normal institutional limits >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (calculated by Cockcroft-Gault formula)

Exclusion Criteria:

  • Concomitant use of warfarin or other Vit K antagonists
  • Central nervous system (CNS) involvement by lymphoma at time of enrollment.
  • Other medical conditions that would potentially interfere with patient participation in this trial.
  • A second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix (unless for other tumor type patient was treated with curative intent at least 2 years previously.)
  • Known human immunodeficiency virus (HIV-1) infection or chronic hepatitis B, or C (Hep B serology positive without active infection will be eligible)
  • Active, clinically serious infection > CTCAE grade 2. Patients may be eligible upon resolution of the infection.
  • Major surgery or significant traumatic injury within 28 days of the first dose of study drug.
  • Use of any other standard chemotherapy, radiation therapy, or experimental drug therapy for the treatment of MCL within 21 days of starting treatment or 5 half life times (whatever is shorter)
  • Patients with grade 3/4 cardiac problems, as defined by the New York Heart Association (NYHA) criteria:
  • History of uncontrolled or symptomatic angina
  • History of uncontrolled arrhythmias
  • Myocardial infarction < 6 months from study entry
  • Uncontrolled or symptomatic congestive heart failure
  • Ejection fraction below the institutional normal limit
  • Any other cardiac condition that, in the opinion of the treatment physician, would make this protocol unreasonably hazardous for the patient
  • Patients unwilling or unable to comply with the protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation Study
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 10-25 mg PO days 1-21
Drug: Lenalidomide
Dose escalation of lenalidomide. Patients will receive 10, 15, 20, or 25 mg PO days 1-21
Other Names:
  • Revlimid
Drug: Ibrutinib
560 mg PO daily
Other Names:
  • Imbruvica
Drug: Rituximab
375 mg/m2 IV Day 1
Other Names:
  • Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the MTD (Measured in mg) Based on the Number of Patients With Adverse Events
Time Frame: 28 Days
Define maximum tolerated dose (MTD) and /or recommended phase II dose for the combinations of Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765) plus lenalidomide / rituximab in relapsed or refractory MCL by assessing the incidence of dose limiting toxicities (DLTs) in cycle 1 through an assessment of adverse events
28 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess Safety Profile Through Review of Adverse Events
Time Frame: Through 28 Days After Discontinuation of Study Drug
Assess safety and tolerability of the combinations through the review of adverse events. Patients will remain on treatment until disease progression or unacceptable toxicity. There is no predetermined length of treatment.
Through 28 Days After Discontinuation of Study Drug
Assess Radiologic Progression-Free Survival
Time Frame: Response is evaluated after 2, 4 and 6 cycles, after initiation of treatment and later every 3 cycles until disease progression or patient taken off study
Assess preliminary anti-tumor activity of the combinations by radiological progression-free survival. Patients will remain on treatment until disease progression or unacceptable toxicity. There is no predetermined length of treatment.
Response is evaluated after 2, 4 and 6 cycles, after initiation of treatment and later every 3 cycles until disease progression or patient taken off study
Assess Radiologic Response Rate
Time Frame: Response is evaluated after 2, 4 and 6 cycles, after initiation of treatment and later every 3 cycles until disease progression or patient taken off study
Assess preliminary anti-tumor activity of the combinations by radiological response rate. Patients will remain on treatment until disease progression or unacceptable toxicity. There is no predetermined length of treatment.
Response is evaluated after 2, 4 and 6 cycles, after initiation of treatment and later every 3 cycles until disease progression or patient taken off study
Assess Drug-drug Interaction of Combination Therapy
Time Frame: Through 28 Days After Discontinuation of Study Drug
Investigate potential drug-drug interaction between Ibrutinib (PCI-32765) plus lenalidomide / rituximab. Patients will remain on treatment until disease progression or unacceptable toxicity. There is no predetermined length of treatment.
Through 28 Days After Discontinuation of Study Drug

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hackensack Meridian Health

Investigators

  • Principal Investigator: Andre Goy, MD, Hackensack Meridian Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 18, 2015

Primary Completion (Actual)

January 3, 2017

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

May 6, 2015

First Submitted That Met QC Criteria

May 13, 2015

First Posted (Estimated)

May 18, 2015

Study Record Updates

Last Update Posted (Actual)

March 24, 2026

Last Update Submitted That Met QC Criteria

March 20, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00005444

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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