Ibrutinib in Patients With Refractory/Relapsed Non-GCB Diffuse Large B-cell Lymphoma Non-candidates to ASCT

NCT02692248 | Completed Phase 2 Results

• 1 other identifier: IBDCL-GELTAMO-2015
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 17

Brief Summary

Multicentric phase II trial to evaluate efficacy and safety of ibrutinib in combination with rituximab, gemcitabine, oxaliplatin and dexamethasone followed by Ibrutinib maintenance in patients with refractory/relapsed non-GCB DLBCL non candidates to autologous stem-cell transplantation (ASCT) An extensive biological study will be conducted in order to further characterize this population of DLBCL patients and correlate the response obtained with the biological profile of the tumor.

Conditions

Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response (OR) Rate

  Overall Response (OR) rate (complete remission + partial response) measured by PET(Positron Emission Tomography)/CT image scan. OR will be assessed by Lugano Classification: Revised Criteria for Response Assessment.

  Treatment responses will be evaluated 30 days after end of study treatment which can be occurred after 2 years and 4 months

Secondary Outcomes (6)

• CR Rate During Induction and Maintenance Phases.

  Complete treatment responses will be evaluated 30 days after end of study treatment which can be occurred after 2 years and 4 months

• Response Duration

  Response duration will be evaluated at any time during the study when tumor response is documented or after end of study treatment which can be occurred after 2 years and 4 months.

• Progression Free Survival

  Progression free survival will be evaluated at any time during the study when first documentation of recurrence, progression, or death or after end of study treatment which can be occurred after 2 years and 4 months

• Event-free Survival

  2 years and 4 months.

• Overall Survival

  2 years

Study Arms (1)

Ibrutinib -R-GEMOX-Dexa

EXPERIMENTAL

Subjects will receive Ibrutinib with R-GEMOX-Dexa followed by Ibrutinib maintenance according to: Induction phase: * Rituximab 375 mg/m2 IV day 1 * Gemcitabine 1000 mg/m2 IV on day 1 or 2 (at investigator discretion). * Oxaliplatine 100 mg/m2 on day 1 or 2 (after Gemcitabine administration); * Dexamethasone 20 mg orally or IV on day 1 and orally on days 2-3. * Ibrutinib 560 mg daily for 14 days. Responding patients will receive 2 (if CR) or 4 (if PR) additional cycles every 14 days.Patients with SD and ABC profile will receive 4 additional cycles. Maintenance phase: Responding patients will receive Ibrutinib 560 mg daily - Continuous cycles until a maximum of 2 years, disease progression or unacceptable toxicity.

Drug: Ibrutinib; Drug: Rituximab; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Dexamethasone

Interventions

Ibrutinib DRUG

Ibrutinib 560 mg daily for 14 days during induction cycles. Maintenance phase: Continuous cycles until disease progression or unacceptable toxicity (maximum of 2 years).

Ibrutinib -R-GEMOX-Dexa

Rituximab DRUG

Rituximab 375 mg/m2 IV day 1 during 4 cycles.

Ibrutinib -R-GEMOX-Dexa

Gemcitabine DRUG

Gemcitabine 1000 mg/m2 IV (30-minute infusion) on day 1 or 2, 4 cycles every 14 days.

Ibrutinib -R-GEMOX-Dexa

Oxaliplatin DRUG

Oxaliplatin 100 mg/m2 (3-hour infusion) on day 1 or 2, after Gemcitabine infusion, 4 cycles every 14 days.

Ibrutinib -R-GEMOX-Dexa

Dexamethasone DRUG

Dexamethasone 20 mg orally or IV on day 1 and orally on days 2-3, 4 cycles every 14 days.

Ibrutinib -R-GEMOX-Dexa

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 histologically diagnosis of diffuse large B-cell lymphoma.
• Subjects must be 18 years of age or older.
• Non-germinal center B-cell-like (GCB) subtype according to Hans algorithm (local laboratories).
• A central review will be performed for confirmation of the germinal center B-cell-like, however even when negative results are reported, the patient will still be part of the study if clinical benefit after cycle 4 is documented (stable disease, partial response and complete response).
• Relapsed or refractory disease after:
• at least 1 prior line of therapy that includes rituximab in combination with chemotherapy, or,
• after previous ASCT, or,
• after reduced intensity conditioning allogeneic transplant, unless patient is receiving immunosuppressive drugs or active graft versus host disease is present at study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Baseline FDG-PET scan demonstrating positive lesions (Deauville 4 or 5) compatible with CT defined anatomical tumor sites.
• Hematology values must be within the following limits:
• absolute neutrophil count (ANC) ≥1000/μL independent of growth factor support.
• platelets ≥100000/μL or ≥50000/μL if bone marrow involvement independent of transfusion support in either situation.
• Biochemical values within the following limits:
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN).

You may not qualify if:

• Prior malignancy other than DLBCL, with the exception of adequately treated basal cell or squamous cell skin tumor, in situ cervical cancer, or other tumor from which the patient has been disease free for at least 2 years or which will not limit survival to \< 2 years (Note: these cases must be discussed with the Principal Investigator).
• Candidates to autologous stem cell transplant.
• \- Young patients with more than a previous line and refractory could be considered as not suitable for autologous stem cell transplant and, therefore, are eligible for this study.
• Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety,interfere with the absorption or metabolism of ibrutinib, or put the study outcomes at undue risk.
• Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis,symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• Treatment with any immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 3 weeks before first dose of study drug.
• Prior treatment with ibrutinib or other BTK inhibitors.
• Central nervous system (CNS) involvement by lymphoma.
• History of stroke or intracranial hemorrhage within 6 months prior to randomization.
• Requires anticoagulation with warfarin or equivalent Vitamin K antagonists.
• Requires treatment with strong CYP3A inhibitors.
• Grade ≥2 toxicity (other than alopecia) related to prior anticancer therapy including radiation.
• Known history of human immunodeficiency virus (HIV), active hepatitis C virus (HCV) (HCV; RNA polymerase chain reaction \[PCR\]-positive) or active Hepatitis B virus (HBV; DNA PCR-positive) infection or any uncontrolled active systemic infection requiring IV antibiotics. Subjects with PCR-negative HBV are permitted in the study.
• Major surgery within 4 weeks before first dose of study drug.

Sponsors & Collaborators

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

Study Sites (17)

Hospital Universitario Son Espases

Palma, Balearic Islands, 07120, Spain

Location

Hospital Especialidades

Jerez de la Frontera, Cádiz, 11407, Spain

Location

Hospital Universitario Donostia

Donostia / San Sebastian, Guipúzcoa, 20080, Spain

Location

Hospital de Navarra

Pamplona, Navarre, 31008, Spain

Location

Complexo Hospitalario Universitario de Vigo

Vigo, Pontevedra, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Hospital Universitario Infanta Leonor

Madrid, 28031, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Clínic Universitari de València

Valencia, 46010, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, 47005, Spain

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

ibrutinib; Rituximab; Gemcitabine; Oxaliplatin; Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; 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; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

The main limitation of the IBDCL trial was the lack of randomization and a parallel control group, that precluded comparison of outcome measures with other existing therapeutic approaches.

Results Point of Contact

• Title: Responsable person designated by the sponsor
• Organization: MFAR

investigacion@mfar.net

+34934344412

Study Officials

• Dolores Caballero, MD

  University of Salamanca

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

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: February 17, 2016
• First Posted: February 26, 2016
• Study Start: April 7, 2016
• Primary Completion: November 8, 2018
• Study Completion: January 19, 2021
• Last Updated: October 10, 2024
• Results First Posted: October 10, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (17)