Safety and Efficacy of Revlimid® (Lenalidomide) With Mabthera® (Rituximab) in Non-Hodgkin's Lymphoma (R2)
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|ClinicalTrials.gov Identifier: NCT01939327|
Recruitment Status : Completed
First Posted : September 11, 2013
Last Update Posted : May 11, 2020
The incidence of non-Hodgkin's lymphoma (NHL) is steadily increasing worldwide. At present, it is the sixth most commonly diagnosed cancer in France, with 10 000 estimated new cases and 5200 deaths annually. An increasing NHL incidence at a rate of 3-4% per year was observed for the 1970s and 1980s. This stabilized in the 1990s, nevertheless still with an annual rise of 1-2%, resulting in almost a doubling of the NHL incidence during last 40 years. This rise has been noted worldwide, particularly in elderly persons >55 years. Increases in high-grade NHL and extranodal disease are predominant. There is about 80% of B-cell histology, approximately 90% of follicular lymphomas and about 70% of aggressive lymphoma patients present with disseminated disease at diagnosis. The prognosis of NHL depends on the histological type, stage and treatment. Indolent lymphomas have a relatively good prognosis with survival time as long as 10 years, but they are usually incurable in advanced stages. Aggressive NHL constitutes about 50% of all cases of NHL in Western Europe. Approximately 50 - 60% of these patients can be cured with immuno-chemotherapy regiments. Subsequently, almost 50% of patients will eventually relapse or become refractory to treatment. The prognosis for patients with refractory or relapsed aggressive NHL is generally poor. The response rates to salvage therapy regimens range from 20 to 40%. Patients who present with refractory disease have the worst prognosis, with a median survival of less than six months. Only a minority of patients can be given high dose chemotherapy, the majority being ineligible due to disease progression.
By modulating the immune system through dendritic cells and NK cells, by changing the cytokine milieu, and by their anti-angiogenic effects, IMiDs in combination with mabthera (rituximab) resulted in augmented in vitro and vivo antitumor effects against B-cell lymphoma.
As concerns the timing of administration and doses of medications, phase I/II studies are ongoing with R-CHOP in combination with Revlimid (Lenalidomide) in DLBCL. The latest presentation is by Nowakowski et al. at ASCO meeting in June 2010. This study determined the maximum tolerated dose of Revlimid(Lenalidomide)administered on days 1-10 with standard R-CHOP (R2-CHOP). NO DLT was found and 25 mg of Revlimid(Lenalidomide)was the recommended dose for phase II with enrollment of 32 patients. These encouraging results permit to introduce in our much less toxic protocol 25 mg of Revlimid(Lenalidomide)as initial dose, with progressive reduction in case of toxicity.
As regards the dose and timing of Mabthera(Rituximab), in DLBCL it was traditionally used as a single 375 mg/m2 injection/cycle. Pre-clinical data suggests that for the optimal NK enhancement Revlimid(Lenalidomide)must be administrated several days (approx. 7 days) before Mabthera(Rituximab)injection. So, our protocol provides Mabthera(Rituximab)IV administration at day 7 of Revlimid(Lenalidomide).
Performed parallel biological investigation of NK status will permit to confirm this hypothesis with possible correction of timing and number of administrations of Mabthera(Rituximab)par cycle.
|Condition or disease||Intervention/treatment||Phase|
|Non-Hodgkin Lymphoma||Drug: Lenalidomide/Rituximab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Single-arm, Open-label Study to Evaluate the Safety and Efficacy of Combination Lenalidomide (Revlimid®) With Rituximab in Subjets With Relapsed or Refractory Diffuse Large b Cell Non-Hodgkin's Lymphoma.|
|Actual Study Start Date :||September 2013|
|Actual Primary Completion Date :||October 2017|
|Actual Study Completion Date :||January 2020|
Association of Lenalidomide and Rituximab
- Response Rate [ Time Frame: at 6 months ]The efficacy is evaluated by the response rate defined as complete and partial response or stable disease.according to Cheson 2007 criteria and by PET-SCAN
- Progression [ Time Frame: at 6 months ]
- Duration of response defined from the time when criteria for response (CR or PR) are met to the first documentation of relapse or progression.
- Time to Progression defined as the time from randomisation to first documentation of objective tumour progression (date of tumour assessment documenting progressive disease) or to death due to lymphoma whichever comes first. Progression is assessed by CT scan and/or bone marrow biopsy according to Cheson criteria modified in 2007.
- Progression free survival defined as the time from inclusion to progression
- Tumor control rate : complete response, complete response unconfirmed, partial response, and stable disease
- safety [ Time Frame: up to 1 year ]The safety of the study treatment will be assessed on occurrence of Adverse Events (AEs), graded based on NCI CTCAE v4.0 classification.
- NK cells [ Time Frame: up to 6 months ]- Biological study of antigenic modulation and immune functions of immunocompetent cells (NK cells, T8 gamma/delta, monocytes/macrophages, neutrophiles) before, during and after treatment.
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): NCT01939327
|Marseille, France, 13009|
|Principal Investigator:||Vadim IVANOV, MD||Institut Paoli-Calmettes|