Dose Finding Study of Ibrutinib Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma
Condition: Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: Lenalidomide; Ibrutinib; Rituximab
Intervention description: Dose escalation of lenalidomide. Patients will receive 10, 15, 20, or 25 mg PO days 1-21; 560 mg PO daily; 375 mg/m2 IV Day 1
Intervention MeSH terms: Rituximab; Lenalidomide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.