Safety and Efficacy of Intensified Chemotherapy Regimens in Aggressive B-cell Lymphomas With MYC Rearrangement (OSR-CARMEN)
A Retrospective Observational Study of the Safety and Efficacy of Intensified Chemotherapy Regimens in Aggressive B-cell Lymphomas With MYC Rearrangement
A multicenter, retrospective, observational drug study using anonymized data from adult patients with aggressive B-cell lymphoma treated with the CARMEN regimen.
The data were collected during normal clinical practice, therefore neither diagnostic approaches nor experimental drugs/devices will be applied.
Aperçu de l'étude
Statut
Les conditions
Description détaillée
igh-grade B-cell lymphomas (HGBCL), including Burkitt lymphoma (BL) and MYC-rearranged HGBCL (double-hit and triple-hit lymphomas), are highly aggressive malignancies characterized by rapid proliferation and poor outcomes when treated with standard chemoimmunotherapy regimens such as R-CHOP. Although intensified treatment approaches have improved outcomes in these patients. Over the past decade, the CARMEN regimen has been adopted in several Italian centers as part of routine clinical practice for patients with Burkitt lymphoma and other aggressive B-cell lymphomas characterized by MYC rearrangements. This multicenter, retrospective, observational study aims to evaluate the real-world outcomes of adult patients with aggressive B-cell lymphomas treated with the CARMEN regimen. The study will include consecutive patients diagnosed with Burkitt lymphoma or MYC-rearranged HGBCL, with or without HIV infection, who received CARMEN as first-line therapy during routine clinical practice. Data will be collected retrospectively from participating centers using anonymized patient records.
The primary objectives are to assess the effectiveness and tolerability of the CARMEN regimen in a large real-world population and to describe treatment outcomes, including response rates, progression-free survival, overall survival, relapse patterns, and treatment-related toxicity. Secondary objectives include the evaluation of outcomes according to lymphoma subtype, HIV status, disease characteristics, and consolidation strategies, as well as comparison with outcomes obtained using alternative first-line chemoimmunotherapy regimens employed in clinical practice.
Because this is a non-interventional observational study, no experimental diagnostic procedures, drugs, or medical devices will be administered. All data derive from routine clinical care, and patient management will not be influenced by study participation.
Approximately 500 patients are expected to be included across participating centers. Enrollment is based on retrospective identification of eligible patients treated between November 2022 and November 2027. The study may be suspended or terminated prematurely if the planned sample size cannot be achieved.
Type d'étude
Inscription (Estimé)
Contacts et emplacements
Lieux d'étude
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Italy
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Milan, Italy, Italie, 20132
- IRCCS Ospedale San Raffaele
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Méthode d'échantillonnage
Population étudiée
La description
Inclusion Criteria:
- Age > 18 years
- Histology of aggressive B-cell lymphoma with MYC rearrangement
- Treatment with CARMEN regimen orwith other chemoimmunotherapy regimens for treatment of aggressive B-cell lymphoma with MYC rearrangement
Exclusion Criteria:
- Participation in clinical protocols that expressly exclude the possibility of participation in other studies
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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Patients treated with the CARMEN regimen
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Patients treated with other chemo-immunotherapy regimens (e.g. GMALL, CODOXM-IVAC, RdaEPOCH, LMB)
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Disease-free-survival (DFS)
Délai: at 2 years from the treatment
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Evaluation of the disease free survival.
The Survival will be estimated using the Kaplan-Meier method.
Comparison between groups using the log-rank test.
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at 2 years from the treatment
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Progression-free survival (PFS)
Délai: at 2 years from the treatment
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Evaluation of the progression-free survival (PFS).
The Survival will be estimated using the Kaplan-Meier method.
Comparison between groups using the log-rank test.
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at 2 years from the treatment
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Overall-Survival (OS)
Délai: at 2 years from the treatment
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Evaluation of the Overall survival (OS).
The Survival will be estimated using the Kaplan-Meier method.
Comparison between groups using the log-rank test.
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at 2 years from the treatment
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Complete remission rate
Délai: at 2 years from treatment
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Evaluation of the complete remission rate, defined according to Cheson criteria, of experimental intensive chemotherapy
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at 2 years from treatment
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Incidence of Treatment-Related Adverse Events and Organ Toxicities During Experimental Intensive Chemotherapy (CARMEN) [Safety and Tolerability]
Délai: at 2 years from the treatment
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All patients who received at least the first day of treatment.
Treatment-related adverse events and organ toxicities will be evaluated according to the NCI-NCIC Common Toxicity Criteria (CTC), version 3.0.
Toxicities will be assessed separately for each treatment phase, and the worst organ toxicity observed in each patient will be considered for analysis.
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at 2 years from the treatment
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Incidence of Treatment-Related Adverse Events and Organ Toxicities During Consolidation, Conditioning, and Autologous Stem Cell Transplantation [Safety and Tolerability]
Délai: at 2 years from the treatment
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Assessment of Safety and Tolerability of the consolidation phase followed by conditioning and autologous stem cell transplantation through the evaluation of treatment-related adverse events and organ toxicities occurring during these treatment phases, according to the NCI-NCIC CTC version 3.0.
Toxicities will be analyzed separately considering the worst organ toxicity observed for each patient.
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at 2 years from the treatment
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Incidence of Treatment-Related Adverse Events and Organ Toxicities During Sequential High-Dose Chemotherapy Intensification [Safety and Tolerability]
Délai: at 2 years from the treatment
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The tolerability of intensification with sequential high-dose chemotherapy in patients with stable disease after, or progressive disease during or after induction chemotherapy will be assessed through the evaluation of treatment-related adverse events and organ toxicities according to the NCI-NCIC CTC version 3.0.
Toxicity assessment will be performed specifically for this treatment phase, and the worst organ toxicity observed in each patient will be considered.
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at 2 years from the treatment
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Overall Treatment Response Rate Across the Entire Experimental Intensive Chemotherapy Program
Délai: at 2 years from the treatment
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The activity of the entire experimental intensive chemotherapy program will be assessed by evaluating treatment response after induction, after consolidation, and at the end of the entire treatment program using whole-body CT, 18FDG-PET, and other positive baseline tests where applicable.
Response will be defined according to the revised response criteria for malignant lymphoma.
The investigator-assessed complete response rate will be used as supportive evidence.
In patients with positive cerebrospinal fluid at baseline, cytological assessment will be be performed before each intrathecal chemotherapy administration; a reduction greater than 50% in cell count will be considered partial response, whereas a smaller reduction will be considered stable disease.
Presence of tumor cells in cerebrospinal fluid will be confirmed by flow cytometry in all samples with ≥4 nucleated cells/μL.
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at 2 years from the treatment
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Collaborateurs et enquêteurs
Parrainer
Publications et liens utiles
Publications générales
- Colombo AL, de Almeida Junior JN, Slavin MA, Chen SC, Sorrell TC. Candida and invasive mould diseases in non-neutropenic critically ill patients and patients with haematological cancer. Lancet Infect Dis. 2017 Nov;17(11):e344-e356. doi: 10.1016/S1473-3099(17)30304-3. Epub 2017 Jul 31.
- Ferreri AJM, Cattaneo C, Lleshi A, Verga L, Allione B, Facchetti F, Ponzoni M, Foppoli M, Ferrari D, Rigacci L, Pecciarini L, Donadoni G, Fumagalli L, Sassone M, Calimeri T, Rossi G, Spina M, Re A. A dose-dense short-term therapy for human immunodeficiency virus/acquired immunodeficiency syndrome patients with high-risk Burkitt lymphoma or high-grade B-cell lymphoma: safety and efficacy results of the "CARMEN" phase II trial. Br J Haematol. 2021 Jan;192(1):119-128. doi: 10.1111/bjh.17188. Epub 2020 Oct 21.
- Ferry A, Rieu P, Le Page C, Elhabazi A, Laziri F, Rieu M. Effect of physical exhaustion and glucocorticoids (dexamethasone) on T-cells of trained rats. Eur J Appl Physiol Occup Physiol. 1993;66(5):455-60. doi: 10.1007/BF00599621.
- Halasz LM, Jacene HA, Catalano PJ, Van den Abbeele AD, Lacasce A, Mauch PM, Ng AK. Combined modality treatment for PET-positive non-Hodgkin lymphoma: favorable outcomes of combined modality treatment for patients with non-Hodgkin lymphoma and positive interim or postchemotherapy FDG-PET. Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):e647-54. doi: 10.1016/j.ijrobp.2012.01.060. Epub 2012 May 18.
- Schmidt E, Thoennissen NH, Rudat A, Bieker R, Schliemann C, Mesters RM, Zuhlsdorf M, Muller-Tidow C, Berdel WE. Use of palifermin for the prevention of high-dose methotrexate-induced oral mucositis. Ann Oncol. 2008 Sep;19(9):1644-9. doi: 10.1093/annonc/mdn179. Epub 2008 May 2.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Autres numéros d'identification d'étude
- OSR-CARMEN retro
Plan pour les données individuelles des participants (IPD)
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Informations sur les médicaments et les dispositifs, documents d'étude
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