Mantle Cell Lyphoma MedDRA version: 18.1 Level: HLT Classification code 10026798 Term: Mantle cell lymphomas System Organ Class: 100000004851
Conditions
Interventions
Trade Name: IMBRUVICA
Product Name: IBRUTINIB
Product Code: PR-1
Pharmaceutical Form: Capsule
INN or Proposed INN: IBRUTINIB
CAS Number: 936563-96-1
Concentration unit: mg milligram(s)
Concentration t
Sponsors
GELTAMO (Grupo Cooperativo Español de Llinfoma/Trasplante Autólogo de Médula Ósea)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects with confirmed diagnosis of Mantle Cell Lymphoma (World Health Organization Classification, WHO 2008). Classical, small-cell variants and marginal-zone variants can be included. 2. Age 18 years or older. 3. Subjects must not have received any prior therapies (excluding diagnostic splenectomy). 4. Asymptomatic patients. 5. Ann Arbor clinical stages I-IV. 6. Eastern Cooperative Oncology Group (ECOG) performance status =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Aggressive histological variants: blastic and pleomorphic variants (blastoid). 2. Proliferation index measured by Ki-67 > 30%. 3. B-cell monoclonal lymphocytosis with MCL phenotype. 4. Eastern Cooperative Oncology Group (ECOG) performance status ?2. 5. Presence of B symptoms or any relevant symptoms related to the MCL. 6. Nodal clinical forms with lymph node enlargement > 2.5 cm (maximum diameter). 7. Cytopenias attributable to MCL: Neutrophil count 2 ULN or altered liver biochemistry (> 3x ULN). 9. Gradual increase in different determinations of serum LDH attributable to MCL that exceeds 20% of the ULN 10. Known CNS infiltration 11. Subjects with expected therapy requirement for MCL in a short time (< 3 months) 12. Patients with active hepatitis B or C infection or HIV infection. Positive test results for chronic HBV infection (defined as positive HBsAg serology) or positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing) will be excluded with the following exceptions. Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing or antiviral prophylaxis. Patients who have protective titters of hepatitis B surface antibody (HBsAb) after vaccination or prior but cured hepatitis B are eligible. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA. 13. Anticoagulation requirement with vitamin K antagonists 14. Past medical history of stroke or intracranial haemorrhage within 6 months prior to inclusion. 15. Required medication with strong CYP3A4/5 inhibitors 16. Any serious comorbidity that makes the patient unacceptable for receiving the treatment 17. Concomitant or previous malignancies the last 2 years other than basal skin cancer or in situ uterine cervix cancer 18. Pregnancy or lactation 19. Major surgery within 4 weeks of inclusion. 20. 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. 21. Vaccinated with live, attenuated vaccines within 4 weeks of randomization. 22. Uncontrolled systemic infection requiring intravenous (IV) antibiotics. 23. 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 put the study outcomes at undue risk.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To explore the efficacy of Ibrutinib plus Rituximab combination as a therapeutic alternative to immuno-chemotherapy (R-CHOP regimen) in indolent forms of Mantle Cell Lynphoma (MCL) by assessing the rate of complete responses achieved at 12 months of treatment;Secondary Objective: 1. To evaluate the efficacy of I+R combination along time in terms of secondary endpoints (ORR at 12 months, PFS, response duration, OS, MRD analysis) 2. To determine the safety and tolerability of ibrutinib in combination with rituximab (including evaluation of health-related quality of life (QOL)) 3. Biological characterization of indolent forms of MCL and their response to I+R by genomic studies;Primary end point(s): Rate of complete remission (CR) achieved at 12 months with Ibrutinib in combination with Rituximab. All the patients will be evaluated with PET-CT and bone marrow biopsy at that point and the international response criteria will be applied;Timepoint(s) of evaluation of this end point: timepoint of evaluation of this end point will be 12 months of patient treatment with Ibrutinib in combination with Rituximab | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Once the treatment is started, there will be a visit before each cycle during the first 12 months, after that, visits every three months until end of follow-up. A visit at day 30 after the end of treatment.;Secondary end point(s): 1. Overall Response Rate (ORR) achieved at 12 months 2. Progression Free Survival 3. Response Duration 4. Rate of negative Minimal residual disease (MRD) at 12 months, time to obtain a molecular response, duration of molecular response. Prognostic value of MRD status. 5. Overall survival. 6. Rates of AEs, SAEs and SUSARs by CTC grade (Version 4.03) during I+R treatment 7. To assess the health-related quality of life (QOL) during treatment. 8. Genomic studies in indolent clinical forms of MCL (IGHV mutational status, DNA copynumber and whole exome sequencing). | — |
Countries
Spain
Contacts
Public ContactAngel Cedillo
Secretaría Científica GELTAMO
Outcome results
None listed