Ibrutinib in Combination With Rituximab in Patients With Indolent Clinical Forms of MCL

NCT02682641 | Active Not Recruiting Phase 2

• 2 other identifiers: GELTAMO-IMCL-20152015-004158-17
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 15

Brief Summary

Phase II study with a two-stage design to evaluate efficacy and safety of ibrutinib in combination with rituximab (I+R) in untreated patients with indolent clinical forms of MCL. An extensive biological study will be conducted in order to further characterize this population of MCL patients and evaluate the response obtained with the mutational profile of the tumor.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Rate of complete remission

  Percentage of patients who are alive and in complete response at 12 months from the date of treatment initiation. All patients will be evaluated with PET- CT and bone marrow biopsy at that time.

  12 months

Secondary Outcomes (8)

• Overall Response Rate (OR)

  12 months

• Progression Free Survival

  7 years

• Response Duration

  7 years

• Minimal residual disease (MRD)

  within 12 months after initiation of study treatment

• Overall survival

  7 years

Study Arms (1)

IBRUTINIB + RITUXIMAB

EXPERIMENTAL

Subjects will receive the ibrutinib in combination with rituximab according to the following schedule: * Ibrutinib 560 mg daily po until disease progression or unacceptable toxicity. In case of sustained negative MRD (at least for 6 months) after 2 years of continuous therapy, ibrutinib will be discontinued. * Rituximab 375 mg/m2 iv day 1,8, 15 and 22 (cycle 1). Rituximab 375 mg/m2 iv, day one of every cycle 3, 5, 7 and 9.

Drug: IBRUTINIB; Drug: Rituximab

Interventions

IBRUTINIB DRUG

Ibrutinib 560 mg daily po for 28 days (cycle one). Continuous cycles until disease progression or unacceptable toxicity.

Also known as: Imbruvica

IBRUTINIB + RITUXIMAB

Rituximab DRUG

Rituximab 375 mg/m2 iv day 1,8, 15 and 22 (cycle 1, 4 doses). Rituximab 375 mg/m2 iv, day one of every other cycle for 4 doses (cycle 3, 5, 7 and 9).

IBRUTINIB + RITUXIMAB

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age 18 years or older.
• Subjects must not have received any prior therapies (excluding diagnostic splenectomy).
• Asymptomatic patients.
• Ann Arbor clinical stages I-IV.
• Eastern Cooperative Oncology Group (ECOG) performance status \<2 (0-1).
• Subjects with a non-nodal MCL presentation with mainly bone marrow or peripheral blood involvement.
• Other asymptomatic clinical presentations are acceptable in case of low tumor burden, including nodal MCL with lymph node enlargement ≤3 cm in the maximum diameter and with low proliferation index (Ki-67 ≤ 30%).
• The following laboratory values at screening: a) Neutrophil count ≥ 1×10e9/L, Hemoglobin level ≥ 100 g/L or platelet count ≥100×10e9/L; b) Transaminases (AST and ALT) ≤ 3 x ULN. c)Total bilirubin ≤1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin; d) Creatinine ≤ 2 x ULN or calculated creatinine clearance ≥ 40 mL/min/1.73 m2.
• Stable disease without evidence of clinical progression criteria for at least 3 months. Patients in prolonged therapeutic abstention may be included.
• Women of childbearing potential and men who are sexually active must be practising a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug.
• Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[-hCG\]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study.
• 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.

You may not qualify if:

• Aggressive histological variants: blastic and pleomorphic variants (blastoid).
• Proliferation index measured by Ki-67 \> 30%.
• B-cell monoclonal lymphocytosis with MCL phenotype
• Eastern Cooperative Oncology Group (ECOG) performance status ≥2. Presence of B symptoms or any relevant symptoms related to the MCL.
• \. Nodal clinical forms with lymph node enlargement \>3 cm (maximum diameter). 7. Cytopenias attributable to MCL: Neutrophil count \< 1×10e9/L, Hemoglobin level \< 100 g/L or platelet count \< 100×10e9/L.
• \. Organ dysfunction related to MCL including creatinine level \> 2 x ULN or altered liver biochemistry (\> 3x ULN).
• \. Gradual increase in different determinations of serum LDH attributable to MCL that exceeds 20% of the ULN.
• \. 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 titers 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.
• \. Required medication with strong CYP3A4/5 inhibitors 16. Any serious comorbidity that makes the patient unacceptable for receiving the treatment.
• \. Concomitant or previous malignancies the last 2 years other than basal skin cancer or in situ uterine cervix cancer.
• \. 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.

Sponsors & Collaborators

• Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea: lead
• Janssen-Cilag, S.A.: collaborator

Study Sites (15)

Hospital Clínic de Barcelona

Barcelona, Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Barcelona, Spain

Location

Institut Català d'Oncologia

Barcelona, Barcelona, Spain

Location

Hospital Universitario Mútua Terrassa

Terrassa, Barcelona, Spain

Location

Hospital Universitario de Burgos

Burgos, Burgos, Spain

Location

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Madrid, Spain

Location

MD Anderson Cancer Center

Madrid, Madrid, Spain

Location

Hospital General Universitario Santa Lucía

Cartagena, Murcia, Spain

Location

Hospital Costa del Sol

Marbella, Málaga, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Sevilla, Spain

Location

Hospital Clínico de Valencia

Valencia, Valencia, Spain

Location

Hospital Universitario Clinico de Salamanca

Salamanca, Spain

Location

Related Publications (1)

• Gine E, de la Cruz F, Jimenez Ubieto A, Lopez Jimenez J, Martin Garcia-Sancho A, Terol MJ, Gonzalez Barca E, Casanova M, de la Fuente A, Marin-Niebla A, Muntanola A, Gonzalez-Lopez TJ, Aymerich M, Setoain X, Cortes-Romera M, Rotger A, Rodriguez S, Medina Herrera A, Garcia Sanz R, Nadeu F, Bea S, Campo E, Lopez-Guillermo A. Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial. J Clin Oncol. 2022 Apr 10;40(11):1196-1205. doi: 10.1200/JCO.21.02321. Epub 2022 Jan 14.

  PMID: 35030036 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ibrutinib; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Eva Giné, MD

  Hospital Clinic of Barcelona

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2016
• First Posted: February 15, 2016
• Study Start: May 18, 2016
• Primary Completion: December 1, 2019
• Study Completion (Estimated): December 1, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (15)