Ibrutinib in Patients With Refractory/Relapsed Non-GCB Diffuse Large B-cell Lymphoma Non-candidates to Autologous Stem Cell Transplantation
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|ClinicalTrials.gov Identifier: NCT02692248|
Recruitment Status : Recruiting
First Posted : February 26, 2016
Last Update Posted : June 27, 2018
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Large B-Cell Lymphoma||Drug: Ibrutinib Drug: Rituximab Drug: Gemcitabine Drug: Oxaliplatin Drug: Dexamethasone||Phase 2|
The use of highly effective rituximab-containing therapy for treating diffuse large B-cell lymphoma (DLBCL) makes it more difficult to salvage relapsed or refractory patients. In addition, patients with advanced age or significant comorbidities, who are consequently not candidates for high-dose consolidative therapy, have a very poor prognosis. Prospective studies investigating new salvage regimens are essential.
The combination of rituximab, gemcitabine and oxaliplatin (R-GEMOX) is an effective salvage regimen for patients with relapsing or refractory DLBCL, with a favourable toxicity profile for unfit and/or elderly patients. Ibrutinib, an oral Bruton's tyrosine kinase inhibitor, is a potent killer of ABC DLBCL cell lines in vitro and in xenografts.
It is expected that the combination of ibrutinib with R-GEMOX-Dexa could be effective and well tolerated. Thus, it is proposed an open-label, non-randomized, multicentre, phase II trial, to investigate the safety and efficacy of the combination of ibrutinib with rituximab, gemcitabine, oxaliplatine and dexamethasone followed by ibrutinib maintenance as salvage therapy for patients with relapsed or refractory non-GCB DLBCL non-candidates to stem cell transplant.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||62 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multicentric Phase II Trial to Evaluate the Efficacy and Safety of Ibrutinib in Combination With Rituximab, Gemcitabine, Oxaliplatin and Dexamethasone Followed by Ibrutinib Maintenance in Patients With Refractory/Relapsed Non-GCB Diffuse Large B-cell Lymphoma Non Candidates to ASCT|
|Study Start Date :||April 7, 2016|
|Estimated Primary Completion Date :||September 2020|
|Estimated Study Completion Date :||September 2020|
Experimental: Ibrutinib -R-GEMOX-Dexa
Subjects will receive Ibrutinib with R-GEMOX-Dexa followed by Ibrutinib maintenance according to:
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.
Ibrutinib 560 mg daily for 14 days during induction cycles. Maintenance phase: Continuous cycles until disease progression or unacceptable toxicity (maximum of 2 years).
Rituximab 375 mg/m2 IV day 1 during 4 cycles.
Gemcitabine 1000 mg/msq IV (30-minute infusion) on day 1 or 2, 4 cycles every 14 days.
Oxaliplatin 100 mg/msq (3-hour infusion) on day 1 or 2, after Gemcitabine infusion, 4 cycles every 14 days.
Dexamethasone 20 mg orally or IV on day 1 and orally on days 2-3, 4 cycles every 14 days.
- Overall Response (OR) rate (complete remission + partial response) measured by PET(Positron Emission Tomography)/CT imagen scan [ Time Frame: Treatment responses will be evaluated 30 days after end of study treatment wich can be ocurred after 2 years and 4 months ]OR will be assessed by Lugano Classification: Revised Criteria for Response Assessment (Cheson et al. 2014)
- CR rate during induction and maintenance phases. [ Time Frame: 2 years ]Complete treatment responses evaluation during 21-35 days after initiation of 6 or 8 cycle of study treatment (depend of treatment responses obtained from cycle 4) and 30 days after end of study treatment which can be occurred after 2 years and 4 months
- Conversion rate from SD (Stable Disease) or PR to PR or CR by PET/CT imagen scan [ Time Frame: 2 years ]Responses conversion rate evaluation after 30 days of the end of the maintenance treatment which can be occurred after 2 years of maintenance study treatment
- Response duration [ Time Frame: 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. ]Response duration defined as the time from the documentation of tumor response to disease progression or death, in the event of no documented recurrence, or start of a new anti - lymphoma treatment because of refractory or persistent disease.
- Progression free survival [ Time Frame: 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 ]Progression free survival defined as the time between start of treatment and the first documentation of recurrence, progression, or death in the event of no documented recurrence, or start of a new anti - lymphoma treatment, due a refractory or persistent disease
- Event-free survival [ Time Frame: 2 years ]Event-free survival defined as the time between start of treatment and the first documentation of adverse events and serious adverse events graded according to NCI CTCAE v4.0
- Overall survival [ Time Frame: 2 years ]Overall survival is defined as the time between the start of treatment and death from any cause. Patients that are withdrawn from the trial or lost of follow-up, will be censored with the date of last contact. Patients who are still alive at the end of the study will be censored at that time.
- Safety and tolerability of ibrutinib in combination rituximab, gemcitabine, oxaliplatin and dexamethasone [ Time Frame: 2 years ]Safety and tolerability will be assessed during any phase of study treatment and 30 days after end of study treatment which can be occurred after 2 years and 4 months and will be classified according to the Common Toxicity CNC
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02692248
|Contact: Dolores Caballero, MDfirstname.lastname@example.org|
|Contact: Alejandro Martín García-Sancho, MDemail@example.com|
|Hospital Universitario Central de Asturias||Recruiting|
|Oviedo, Asturias, Spain, 33011|
|Contact: Ángel Ramírez Páyer, MD firstname.lastname@example.org|
|Principal Investigator: Ángel Ramírez Páyer, MD|
|Jerez de la Frontera, Cádiz, Spain, 11407|
|Contact: Mª José Ramírez, MD email@example.com|
|Principal Investigator: Mª José Ramírez, MD|
|Hospital Universitario Donostia||Recruiting|
|Donostia San Sebastian, Guipúzcoa, Spain, 20080|
|Contact: Izaskun Ceberio, MD IZASKUN.CEBERIOECHECHIPIA@osakidetza.eus|
|Principal Investigator: Izaskun Ceberio, MD|
|Hospital Universitario Son Espases||Recruiting|
|Palma, Islas Baleares, Spain, 07120|
|Contact: Antonio Gutiérrez, MD firstname.lastname@example.org|
|Principal Investigator: Antonio Gutiérrez, MD|
|Hospital de Navarra||Recruiting|
|Pamplona, Navarra, Spain, 31008|
|Contact: Mª Cruz Viguria, MD email@example.com|
|Principal Investigator: Mª Cruz Viguria, MD|
|Complexo Hospitalario Universitario de Vigo||Recruiting|
|Vigo, Pontevedra, Spain|
|Contact: Ana Margarita Martínez Castro, MD firstname.lastname@example.org|
|Principal Investigator: Ana Margarita Martínez Castro, MD|
|Hospital Universitario Vall d'Hebron||Recruiting|
|Barcelona, Spain, 08035|
|Contact: Pau Abrisqueta, MD email@example.com|
|Principal Investigator: Pau Abrisqueta, MD|
|Hospital Clínic de Barcelona||Recruiting|
|Barcelona, Spain, 08036|
|Contact: Eva Giné, MD EGINE@clinic.ub.es|
|Principal Investigator: Eva Giné, MD|
|Complejo Hospitalario de Jaén||Recruiting|
|Jaén, Spain, 23007|
|Contact: Soledad Duran Nieto, MD firstname.lastname@example.org|
|Principal Investigator: Soledad Durán Nieto, MD|
|Hospital Universitario Infanta Leonor||Recruiting|
|Madrid, Spain, 28031|
|Contact: José Antonio Hernández Rivas, MD email@example.com|
|Principal Investigator: Jose Antonio Hernández Rivas, MD|
|MD Anderson Cancer Center||Recruiting|
|Madrid, Spain, 28033|
|Contact: Adolfo de la Fuente, MD firstname.lastname@example.org|
|Principal Investigator: Adolfo de la Fuente, MD|
|Hospital Universitario 12 de Octubre||Recruiting|
|Madrid, Spain, 28041|
|Contact: Carlos Grande, MD email@example.com|
|Principal Investigator: Carlos Grande, MD|
|Hospital General Universitario Morales Meseguer||Recruiting|
|Murcia, Spain, 30008|
|Contact: Jose Javier Sánchez Blanco, MD firstname.lastname@example.org|
|Principal Investigator: Jose Javier Sánchez Blanco, MD|
|Hospital Universitario Virgen del Rocío||Recruiting|
|Sevilla, Spain, 41013|
|Contact: Fátima de la Cruz, MD email@example.com|
|Principal Investigator: Fátima de la Cruz, MD|
|Hospital Clínic Universitari de València||Recruiting|
|Valencia, Spain, 46010|
|Contact: Mª José Terol, MD firstname.lastname@example.org|
|Principal Investigator: Mª Jose Terol, MD|
|Hospital Universitario y Politécnico La Fe||Recruiting|
|Valencia, Spain, 46026|
|Contact: Rafael Andreu, MD email@example.com|
|Principal Investigator: Rafael Andreu, MD|
|Hospital Clínico Universitario de Valladolid||Recruiting|
|Valladolid, Spain, 47005|
|Contact: Mª Jesús Peñarrubia, MD firstname.lastname@example.org|
|Principal Investigator: Mª Jesús Peñarrubia, MD|
|Study Chair:||Dolores Caballero, MD||Hospital Universitario de Salamanca|