A Trial of Ibrutinib, Lenalidomide and Rituximab for Patients With Relapsed/Refractory Mantle Cell Lymphoma (PHILEMON)

April 22, 2020 updated by: Lund University Hospital

A Phase II Trial of Ibrutinib, Lenalidomide and Rituximab for Patients With Relapsed/Refractory Mantle Cell Lymphoma

In this trial, patients with mantle cell lymphoma will be included, treatment with lenalidomide, rituximab and ibrutinib will be administered in an induction phase for up to 12 cycles, cycle length 28 days. Patients with complete remission, partial response or stable disease will enter a maintenance phase with treatment with ibrutinib and rituximab until progression of disease.

The primary objective is to evaluate overall response rate, based on PET and CT.

Study Overview

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

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

      • Copenhagen, Denmark
        • Rigshospitalet
      • Helsinki, Finland
        • Helsinki University Hospital
      • Oslo, Norway, 0424
        • Norwegian Radium Hospital
      • Lund, Sweden, 221 85
        • Lund University Hospital
      • Uppsala, Sweden, 751 85
        • Uppsala Akademiska Hospital

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

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age over 18 years
  • Histologically confirmed (according to the WHO 2008, and upcoming 2015 classification) mantle cell lymphoma stage II-IV
  • Received at least 1 prior rituximab-containing chemotherapy regimen
  • Documented relapse or disease progression following the last anti-mantle cell lymphoma treatment
  • At least 1 measurable site of disease (over 1.5 cm long axis)
  • WHO performance status 0-3
  • Written informed concent
  • Female subjects of childbearing potential must:

    1. Understand that the study medication is expected to have a teratogenic effect
    2. Agree to use, and be able to comply with, highly effective contraception without interruption, 4 weeks Before start study drug, throughout study drug therapy (including dose interruptions) and for 12 months after the end of study drug therapy, even if she has amenorrhoea
    3. Women of childbearing potential must have a negative serum (beta-human ionic gonadotropin or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
  • Male subjects must:

    1. Agree to use condoms throughout study drug therapy, during any dose interruption and for 3 months after cessation of study therapy if their partner is of childbearing potential and has no contraception
    2. Agree not to donate semen during study drug therapy and for 3 months after end of study drug therapy
  • All subjects must agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy
  • All subjects must agree not to share study medication with another person and to return all unused study drug to the investigator
  • Absolute neutrophil Count (ANC) ≥ 1000/mm3
  • Platelets ≥ 100,000/mm3 or ≥50,000/mm3 if bone marrow involvement independent of transfusion support in either situation
  • Alanine aminotransferase (ALT) and aspartate aminotransferase ≤ 3 x upper limit of normal (ULN).
  • Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
  • Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockcroft-Gault) ≥ 40 mL/min/1.73 m2
  • 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

Exclusion Criteria:

  • Chemotherapy or radiotherapy within 3 weeks, therapeutic antibodies within 4 weeks, radioimmunotherapy within 10 weeks, or major surgery within 4 weeks of inclusion
  • Known central nervous system lymphoma
  • Other active malignancy
  • Psychiatric illness or condition which could interfere with the subjects' ability to understand the requirements of the study
  • Requirement of corticosteroid therapy at a dose > 10 mg prednisolone/day
  • Major surgery within 4 weeks of inclusion
  • History of stroke or intracranial hemorrhage within 6 months prior to inclusion
  • Requirement of anticoagulation treatment with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon)
  • Requirement of treatment with strong or moderate CYP3A inhibitors
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrythmias, 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
  • Vaccination with live, attenuated vaccines within 4 weeks of inclusion
  • Known history of human immunodeficiency virus (HIV) or Active hepatitis C Virus or Active Hepatitis B Virus infection or any uncontrolled Active systemic infection requiring intravenous antibiotics
  • 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 lenalidomide tablets, or put the study outcomes at undue risk
  • Known hypersensitivity or allergy to rituximab, lenalidomide or ibrutinib

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lenalidomide, ibrutinib and rituximab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate.
Time Frame: Change of tumor burden meassured from baseline during treatment of maximum 144 weeks.
Tumor evaluation will be performed with CT/PET for maximum 144 weeks. Discontinuation of evaluation if the patient develops progressive disease.
Change of tumor burden meassured from baseline during treatment of maximum 144 weeks.

Collaborators and Investigators

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

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.

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

April 1, 2015

Primary Completion (Actual)

December 31, 2019

Study Completion (Actual)

December 31, 2019

Study Registration Dates

First Submitted

May 26, 2015

First Submitted That Met QC Criteria

May 28, 2015

First Posted (Estimate)

June 2, 2015

Study Record Updates

Last Update Posted (Actual)

April 24, 2020

Last Update Submitted That Met QC Criteria

April 22, 2020

Last Verified

April 1, 2020

More Information

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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