A phase II trial of ibrutinib, lenalidomide and rituximab for patients with relapsed/refractory mantle cell lymphoma.

Phase 1

• Conditions: Relapsed/refractory mantle cell lymphoma; MedDRA version: 17.1Level: LLTClassification code 10026799Term: Mantle cell lymphoma NOSSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2013-005541-36-FI
• Lead Sponsor: ordic Lymphoma Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-02-20
• Study Completion: 2019-12-31
• Last Update Posted: 24 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Age >18 years
2. Histologically confirmed (according to the WHO 2008, and upcoming 2015 classification) mantle cell lymphoma stage II-IV,
3. Received at least 1 prior rituximab-containing chemotherapy regimen.
4. Documented relapse or disease progression following the last anti-MCL treatment
5. At least 1 measurable site of disease (>1.5 cm long axis)
6. WHO performance status 0 – 3
7. Written informed consent.
8. Female subjects of childbearing potential must:
a. Understand that the study medication is expected to have a teratogenic risk
b. Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 3 months after
the end of study drug therapy, even if she has amenorrhoea.
c. Women of childbearing potential must have a negative serum (betahuman chorionic gonadotropin [ß-hCG]) or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for
this study.
9. Male subjects must
a. Agree to use condoms throughout study drug therapy, during any dose interruption and for one month after cessation of study therapy if their partner is of childbearing potential and has no contraception.
b. Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
10. All subjects must
a. Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
b. Agree not to share study medication with another person and to return all unused study drug to the investigator.
11. Hematology values must be within the following limits:
a. Absolute neutrophil count (ANC) = 1000/mm3 independent of growth factor support
b. Platelets =100,000/mm3 or =50,000/mm3 if bone marrow involvement independent of transfusion support in either situation
12. Biochemical values within the following limits:
a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x upper limit of normal (ULN)
b. Total bilirubin = 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
c. Serum creatinine = 2 x ULN or estimated Glomerular Filtration Rate (Cockroft-Gault) = 40 mL/min/1.73m2
13. 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

1. Chemotherapy or radiotherapy within 3 weeks, therapeutic antibodies within 4 weeks, radioimmunotherapy within 10 weeks, or major surgery
within 4 weeks of inclusion.
2. Known central nervous system lymphoma.
3. Other active malignancy.
4. Psychiatric illness or condition which could interfere with the subjects' ability to understand the requirements of the study.
5. Requirement of corticosteroid therapy at a dose >10 mg prednisolone/day.
6. Major surgery within 4 weeks of inclusion.
7. History of stroke or intracranial hemorrhage within 6 months prior to inclusion.
8. Requirement of anticoagulation treatment with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon).
9. Requirement of treatment with strong or moderate CYP3A inhibitors (see Appendix 4).
10. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, 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.
11. Vaccination with live, attenuated vaccines within 4 weeks of inclusion.
12. 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 (IV) antibiotics.
13. 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.
14. Known hypersensitivity or allergy to rituximab, lenalidomide or ibrutinib.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluation of overall response rate, based on PET and CT, with lenalidomide, ibrutinib and rituksimab in relapsed/refractory mantle cell lymphoma patients.;Secondary Objective: Response duration<br>Complete remission rate with and without PET<br>Health-related quality of life<br>Molecular remission rate by PCR<br>Molecular remission duration<br>Progression-free survival<br>Overall survival<br>• Safety<br>• Evaluation of biomarkers for efficacy<br>;Primary end point(s): The primary efficacy variable is the evaluation of maximal overall response rate with PET and CT (OOR), with lenalidomide, rituximab and ibrutimin, in patients with relapsed or refractory mantle cell lymphoma.;Timepoint(s) of evaluation of this end point: During study treatment at weeks 10, 22, 34, 46.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Response duration<br>Complete remission rate with and without PET<br>Health-related quality of life<br>Molecular remission rate by PCR<br>Molecular remission duration<br>Progression-free survival<br>Overall survival<br>• Safety<br>• Evaluation of biomarkers for efficacy<br>;Timepoint(s) of evaluation of this end point: During study treatment, and until subjects death, which is the last timepoint.