Clinical Trials /

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

NCT02446236

Description:

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.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dose Finding Study of Ibrutinib Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: Pro 5444
  • NCT ID: NCT02446236

Conditions

  • Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
LenalidomideRevlimidDose Escalation Study
IbrutinibImbruvicaDose Escalation Study
RituximabRituxanDose Escalation Study

Purpose

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.

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).
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation StudyExperimentalIbrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 10-25 mg PO days 1-21
  • Lenalidomide
  • Ibrutinib
  • Rituximab

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the MTD through number of patients with adverse events
Time Frame:28 Days
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:assess safety profile through review of adverse events
Time Frame:28 Days
Safety Issue:
Description:Assess safety and tolerability of the combinations through the review of adverse events

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hackensack Meridian Health

Last Updated

October 4, 2019