"MIRO" Molecularly Oriented Immuno-radio-therapy (FIL_MIRO)
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|ClinicalTrials.gov Identifier: NCT02710643|
Recruitment Status : Active, not recruiting
First Posted : March 17, 2016
Last Update Posted : December 28, 2020
Phase II prospective multicenter study for stage I/II Follicular Lymphoma treated with involved-field radiotherapy (IFRT) at doses of 24 Gy) with or without Ofatumumab for 8 weekly doses on molecular basis. Patients with positive basal Bcl-2 will be followed every 3 months and with Bcl-2 detection every 6 months for 3 years. Patient with negative basal Bcl-2 will be followed every 3 months without further Bcl-2 detection.
Ofatumumab treatment will be administered to:
- Patients with positive basal PCR for Bcl-2-IgH rearrangement in BM and/or PB, resulting still positive after IFRT;
- Patients with positive basal PCR for Bcl-2-IgH in
|Condition or disease||Intervention/treatment||Phase|
|Follicular Lymphoma, Grade 1 Follicular Lymphoma, Grade 2 Follicular Lymphoma Grade 3A||Drug: OFATUMUMAB||Phase 2|
Stage I/IIA follicular lymphoma (FL) is considered a localized disease that can be adequately treated with radiotherapy alone. This strategy is recommended by the guidelines of the "Società Italiana di Ematologia" (SIE) and of the "European Society for Medical Oncology" (ESMO) The accurate definition of the truly localised forms represents a crucial issue in order to ensure an appropriate treatment design for such patients. The characteristic t(14;18) translocation, which leads to the over-expression of the Bcl-2 gene, is found in approximately 85% of FL; cells bearing this translocation can be detected in the peripheral blood (PB) or bone marrow (BM) by polymerase chain reaction (PCR).
PCR for the t(14;18) translocation provides a sensitive device to identify the presence of minimal non-Hodgkin lymphoma (NHL) cell contamination. Previous experiences have demonstrated that despite the limited stage, Bcl-2/IgH+ cells can be found at diagnosis in PB and/or BM of the majority of the patients. After treatment with local radiotherapy confined to the involved lymph node(s) only, disappearance of circulating Bcl-2/IgH+ cells in PB and/or BM was demonstrated in approximately 60% of positive patients. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl-2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was <1:100 000.
Anti-CD20 monoclonal antibody treatment has clearly demonstrated, both alone and in combination with chemotherapy and radiotherapy, a high therapeutic potential in FL. A significant impact of treatment with the anti CD20 monoclonal antibody in reducing the minimal residual disease in FL has been demonstrated in several studies when used as consolidation or during the maintenance phase.
No data are currently available concerning the ability of anti-CD20 antibody treatment in reducing the proportion of Bcl-2 positive residual cells after radiotherapy in localized FL. The objective of this study is to take advantage of the therapeutic potential of anti-CD20 monoclonal antibody to reduce or eliminate minimal residual disease in patients with FL in localized stage (I/II) after conventional treatment with local radiotherapy of the involved site(s). The effectiveness of anti-CD20 monoclonal antibody treatment will be determined by the proportion of negativization of residual Bcl-2 positive cells after radiotherapy, evaluated by qualitative and quantitative PCR detection of viable Bcl-2/IgH rearranged cells in PB and/or BM.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||110 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||"MIRO" (Molecularly Oriented Immuno - Radio -Therapy): Multicenter Phase II Study for the Treatment of the Molecular Basis of Stage I / II Follicular Lymphoma With Local Radiotherapy With / Without Ofatumumab|
|Study Start Date :||October 2014|
|Actual Primary Completion Date :||April 2018|
|Estimated Study Completion Date :||October 2021|
No Intervention: MRD - BEFORE RT
Patients who had negative baseline Bcl-2 in PB and BM will not undergo further treatment after radiotherapy; they will not repeat Bcl-2 during subsequent follow-up visits.
No Intervention: MRD + BEFORE RT AND MRD - AFTER RT
Patients who had positive baseline Bcl-2 in PB and / or BM and become negative after local radiotherapy will not undergo further treatment.
Experimental: MRD + BEFORE RT AND MRD + AFTER RT
Patients who had positive baseline Bcl-2 in PB and / or BM and remain positive after local radiotherapy get Ofatumumab (8 weekly infusion of 1000 mg total dose).
Patients Bcl-2 negativized either after radiotherapy or after Ofatumumab, who became Bcl-2 positive during the follow-up monitoring will be treated/retreated with Ofatumumab 8 weekly infusions at the conventional dose of 1000 mg; Bcl-2 monitoring will be continued subsequently according to the program.In case of persistent positive PCR after Ofatumumab the treatment will not be repeated.
8 weekly infusion of 1000 mg total dose
Other Name: ARZERRA
- Bcl-2 negativization after Ofatumumab [ Time Frame: 4 YEARS FROM ENROLLMENT ]The proportion of Bcl-2 negativization after Ofatumumab treatment will be estimated by the proportion, and its confidence interval, of residual Bcl-2 positive cases after radiotherapy, which will became negative after Ofatumumab treatment
- Clinical response rate [ Time Frame: 4 YEARS FROM ENROLLMENT ]Clinical response rate will be evaluated by the proportion and its confidence interval of patients achieving overall response (OR) complete response (CR) and partial response (PR).
- Overall response [ Time Frame: 4 YEARS FROM ENROLLMENT ]overall response (OR)
- Partial response [ Time Frame: 4 YEARS FROM ENROLLMENT ]partial response (PR)
- Complete response [ Time Frame: 4 YEARS FROM ENROLLMENT ]complete response (CR)
- Progression Free Survival [ Time Frame: 4 YEARS FROM ENROLLMENT ]Progression Free Survival (PFS) is defined as the length of time between the date of registration and the earliest date of disease progression or death due to any cause; If the patients doesn't not have a documented date of progression or death, the PFS will be censored at the date of last adequate assessment. Relapse Free Survival (RFS) is defined as the length of time between the achievement of Complete Remission (CR) and Relapse of disease
- Relapse Free Survival [ Time Frame: 4 YEARS FROM ENROLLMENT ]Relapse Free Survival (RFS) is defined as the length of time between the achievement of Complete Remission (CR) and Relapse of disease
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): NCT02710643
|Study Chair:||Alessandro Pulsoni, MD||Policlinico Umberto I - Università "La Sapienza" - Istituto Ematologia|