Ibrutinib in Combination With Rituximab in Patients With Indolent Clinical Forms of MCL
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|ClinicalTrials.gov Identifier: NCT02682641|
Recruitment Status : Active, not recruiting
First Posted : February 15, 2016
Last Update Posted : May 7, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Mantle Cell Lymphoma||Drug: IBRUTINIB Drug: Rituximab||Phase 2|
Patients with mantle cell lymphoma (MCL) have a median survival of 3-5 years despite treatment. Indeed, the best therapeutic approach for different patients with MCL remains to be established, coexisting different options of immunochemotherapy regimes which may include autologous transplantation in first-line treatment or rituximab maintenance.
Moreover, last years MCL starts to be recognized as a heterogeneous disease both from biological and clinical stand points. For instance, MCL cases with a non-nodal clinical presentation, usually have distinctive biological features such as SOX-11 negativity, hypermutated IGHV genes and a low number of genetic lesions associated. The outcome of these cases is much more favourable compared to conventional MCL, reaching median survivals over 7 to 10 years even receiving less intensive treatments. In addition to that, up to 30% of the patients with newly diagnosed MCL can be safely deferred from initial therapy until progression . Therapeutic abstention may be prolonged for more than one year in 50% of cases. These patients usually show longer survivals from the start of treatment compared to patients immediately treated after diagnosis. Therefore, all these observations indicate that there are indolent clinical forms in MCL, so its clinico-biological identification is crucial to tailor treatment appropriately. However, at present there is no consensus on the diagnostic criteria or treatment recommendations in cases of indolent MCL. This results in difficulties for the identification of these forms in the clinical practice as well as with a certain therapeutic in definition, as indolent forms of MCL can be treated either with therapeutic abstention until progression or receive immediate treatment with conventional or more intensive immuno-chemotherapy regimes, which may even include an autologous hematopoietic stem cell transplantation. With the emergence of new biological agents in the therapeutic arsenal of MCL arises the question whether a completely different approach with new drugs and chemotherapy-free could be more appropriate in selected subsets of patients such as indolent MCL forms.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 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 in Patients With Indolent Clinical Forms of Mantle Cell Lymphoma|
|Actual Study Start Date :||May 18, 2016|
|Actual Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||January 2023|
Experimental: IBRUTINIB + RITUXIMAB
Subjects will receive the ibrutinib in combination with rituximab according to the following schedule:
Ibrutinib 560 mg daily po for 28 days (cycle one). Continuous cycles until disease progression or unacceptable toxicity.
Other Name: Imbruvica
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).
- Rate of complete remission [ Time Frame: 12 months ]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.
- Overall Response Rate (OR) [ Time Frame: 12 months ]Including complete response and partial response according to the International Response Criteria for Non- Hodgkin Lymphoma
- Progression Free Survival [ Time Frame: 7 years ]Percentage of patients without progression of disease
- Response Duration [ Time Frame: 7 years ]Length of time between
- Minimal residual disease (MRD) [ Time Frame: within 12 months after initiation of study treatment ]Proportion of subjects who are MRD negative (ie, less than the lower limit of detection for the MRD assay).
- Overall survival [ Time Frame: 7 years ]Percentage of patients alive from first dose of treatment to end of follow-up.
- Adverse Events (AEs), Serious Adverse Events (SAES) and Suspected Unexpected Serious Adverse Reactions (SUSARs) [ Time Frame: 7 years ]Number of events classified according to the Common Toxicity Criteria of the National Cancer Institute (CTC AE V 4.03).
- Score of the EORTC quality of life questionnaire QLQ-30 [ Time Frame: 12 months ]Health related quality of life questionnaire
- Secore of the FACT-LYM [ Time Frame: 12 months ]Health related quality of life questionnaire
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): NCT02682641
|Hospital Universitario Mútua Terrassa|
|Terrassa, Barcelona, Spain|
|Hospital Universitario Fundación Alcorcón|
|Alcorcón, Madrid, Spain|
|Hospital General Universitario Santa Lucía|
|Cartagena, Murcia, Spain|
|Hospital Costa del Sol|
|Marbella, Málaga, Spain|
|Hospital Clínic de Barcelona|
|Barcelona, Spain, 08036|
|Hospital de la Santa Creu i Sant Pau|
|Hospital Universitario Vall d'Hebron|
|Institut Català d'Oncologia|
|Hospital Universitario de Burgos|
|Hospital Universitario 12 de Octubre|
|Madrid, Spain, 28041|
|Hospital Universitario Ramon y Cajal|
|MD Anderson Cancer Center|
|Hospital Universitario Clinico de Salamanca|
|Hospital Universitario Virgen del Rocio|
|Hospital Clínico de Valencia|
|Study Chair:||Eva Giné, MD||Hospital Clinic of Barcelona|