Ignite Creation Date:
2024-05-06 @ 8:03 PM
Last Modification Date:
2024-10-26 @ 3:19 PM
Study NCT ID:
NCT06235047
Status:
COMPLETED
Last Update Posted:
2024-01-31
First Post:
2024-01-23
Brief Title:
Liposomal Doxorubicin-containing Front-line Treatment in Elderly Patients With HL HL-MVD
Sponsor:
Federico II University
Organization:
Federico II University
Study Overview
Official Title:
Liposomal Doxorubicin-containing Front-line Treatment in Elderly Patients With Classic Hodgkin Lymphoma a Multicenter Phase II Study
Status:
COMPLETED
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Study on the use of a polychemotherapy scheme based on liposomal doxorubicin vinblastine and dacarbazine MVD as first line in the therapy of elderly patients affected by classic Hodgkin lymphoma
Detailed Description:
Classic Hodgkin lymphoma c-HL is a neoplasm that originates from B lymphocytes and represents 10 of all lymphomas The most affected age group is between 20 and 30 years of age with a second peak in the epidemiological distribution involving patients over 60 years of age
Elderly patients often present with already advanced disease stages and B symptoms On the other hand these patients often have multiple comorbidities and reduced fitness and this can limit the therapeutic possibilities with curative intent in terms of doses and adherence to the timing foreseen by the therapeutic protocol
The optimal therapy for this category of patients is not yet well defined In fact the prognosis of these patients is typically poor
The ABVD regimen doxorubicin ie Adriamycin Bleomycin Vinblastine Dacarbazine is a therapeutic option for elderlyunfit patients but is associated with considerable toxicity and mortality In particular mortality rates due to lung damage from Bleomycin are between 4-24 and mortality rates due to cardiac damage are reported in elderly patients suffering from c-HL and treated with regimens based on anthracyclines of which doxorubicin belongs part which fluctuate between 6 and 15
Non-pegylated liposomal anthracycline NPLD was initially used in patients with breast cancer and this particular formulation spares tissues characterized by tight capillary junctions such as cardiac muscle tissue from the direct cytotoxic effect of doxorubicin
Regimens based on NPLD associated with bleomycin vinblastine and dacarbazine have been studied for the first-line treatment of cardiac patients with c-HL and NPLD has been shown to accumulate in macrophages associated with tumor tissue as well as in the spleen liver lung and bones that act as long-release reservoirs with a likely prolonged therapeutic effect
The aim of the present project is to investigate the front-line use of the MVD polychemotherapeutic regimen NPLD Bleomycin and Dacarbazine for elderly patients suffering from c-HL in terms of Overall Survival Progression-Free Survival FDG-PETCT negativity rate at the end of therapy toxicity and feasibility
This was a retrospective single-center study conducted in the Hematology Unit of the Federico II University of Naples Italy in which patients aged 60 years with previously untreated biopsy-proven c-HL were identified in the database of the Hematology Unit of the Federico II University from 1 January 2013 to 1 January 2023 All necessary approvals were obtained from our ethics committee The study was undertaken in accordance with the Declaration of Helsinki All patients provided written informed consent for data analysis
The primary objective of the study was to evaluate whether the front-line therapy without bleomycin by using NPLD-containing regimen ie Myocet TM with its pharmacokinetic and pharmacodynamic advantages in terms of efficacy and safety could improve OS in older adults with c-HL with extensive disease Other objectives were PFS EoT overall response rate by using FDG-PET scans interpreted with the Deauville scale DS 5-point scoring system according to the Lugano Classification hematologic and extra-hematologic toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 50 and feasibility arbitrarily defined as 5 patients receiving 85 of the planned dose Noteworthy the cardiologic toxicity profile was established by using the echocardiography assessment of global systolic longitudinal myocardial strain GLS as well as left ventricular ejection fraction LVEF according to the guidelines of the Task Force for Cancer Treatments and Cardiovascular Toxicity of the European Society of Cardiology ESC
The schedule of study treatment is shown in detail in Table 1 The dosage of Myocet TM in the MVD scheme was well within the ceiling dose of 785 mgm 2 the median lifetime dose reported for NPLD at the onset of cardiotoxicity Patients were scheduled to receive six cycles of therapy with MVD which consisted of 1-day outpatient iv infusions of Myocet TM at a dose of 25 mgm 2 plus vinblastine 6 mgm 2 and dacarbazine 375 mgm 2 on days 1 and 14 of each course every 28 days for twelve administrations Planned cumulative dose-intensity of NPLD was 300 mgm 2
For those cases with initial large nodal mass defined as systemic adenopathy with the largest diameter 5 cm consolidation radiotherapy c-RT at 30 Gy was given after EoT PET assessments following the scheduled 6 MVD cycles on residual bulky area that is containing post-chemotherapy FDG-PET negative nodes of size 20 cm at CT scans as already reported
FDG-PET examinations were conducted at staging EoT and thereafter every 3-6 months FDG-PET results were reported according to the DS score using visual assessment followed by quantitative verification as already described Negative FDG-PET scans were defined as DS 3 score and positive FDG-PET scans were defined as DS 4 and 5 scores Supplemental data FDG- PET assessments All patients were scheduled to undergo a full cardiologic examination 2D echocardiography and speckle tracking echocardiography STE at baseline interim EoT and within six months from the end of all antineoplastic treatments
Clinical cardiologist experts in echocardiography analyzed each study for standard echocardiography and strain measurements
Physical examination and bone marrow biopsy were also performed at baseline and then at physicians discretion Routine blood laboratory test monitoring was performed before every cycle of chemotherapy for each patient
OS was defined as the time from the date of HL diagnosis to the date of last follow-up or death for any cause PFS was defined as the time from day 1 of MVD first dose to disease progressionrelapse event death from any cause event or last follow-up visit censoring All efficacy and safety evaluations were performed in patients who received at least one course of MVD Patients characteristics response rate toxicity and safety data were reported descriptively as number and percentage or as median and range Survival curves were estimated by the Kaplan-Meier method Cox regression analysis was used to estimate the hazard ratio HR and the 95 confidence interval CI for the treatment effect on OS and PFS The evaluated factors included age stratification years 60-69 vs 70-79 vs 80 B symptoms large nodal mass nodal andor extra-nodal sites involved stage IV and international prognostic score IPS risk group at baseline Differences between groups were tested by the log-rank test and student-T test The P value for statistical significance was set at 005 for all evaluations Statistical analysis was performed using R software version 41
Elderly patients often present with already advanced disease stages and B symptoms On the other hand these patients often have multiple comorbidities and reduced fitness and this can limit the therapeutic possibilities with curative intent in terms of doses and adherence to the timing foreseen by the therapeutic protocol
The optimal therapy for this category of patients is not yet well defined In fact the prognosis of these patients is typically poor
The ABVD regimen doxorubicin ie Adriamycin Bleomycin Vinblastine Dacarbazine is a therapeutic option for elderlyunfit patients but is associated with considerable toxicity and mortality In particular mortality rates due to lung damage from Bleomycin are between 4-24 and mortality rates due to cardiac damage are reported in elderly patients suffering from c-HL and treated with regimens based on anthracyclines of which doxorubicin belongs part which fluctuate between 6 and 15
Non-pegylated liposomal anthracycline NPLD was initially used in patients with breast cancer and this particular formulation spares tissues characterized by tight capillary junctions such as cardiac muscle tissue from the direct cytotoxic effect of doxorubicin
Regimens based on NPLD associated with bleomycin vinblastine and dacarbazine have been studied for the first-line treatment of cardiac patients with c-HL and NPLD has been shown to accumulate in macrophages associated with tumor tissue as well as in the spleen liver lung and bones that act as long-release reservoirs with a likely prolonged therapeutic effect
The aim of the present project is to investigate the front-line use of the MVD polychemotherapeutic regimen NPLD Bleomycin and Dacarbazine for elderly patients suffering from c-HL in terms of Overall Survival Progression-Free Survival FDG-PETCT negativity rate at the end of therapy toxicity and feasibility
This was a retrospective single-center study conducted in the Hematology Unit of the Federico II University of Naples Italy in which patients aged 60 years with previously untreated biopsy-proven c-HL were identified in the database of the Hematology Unit of the Federico II University from 1 January 2013 to 1 January 2023 All necessary approvals were obtained from our ethics committee The study was undertaken in accordance with the Declaration of Helsinki All patients provided written informed consent for data analysis
The primary objective of the study was to evaluate whether the front-line therapy without bleomycin by using NPLD-containing regimen ie Myocet TM with its pharmacokinetic and pharmacodynamic advantages in terms of efficacy and safety could improve OS in older adults with c-HL with extensive disease Other objectives were PFS EoT overall response rate by using FDG-PET scans interpreted with the Deauville scale DS 5-point scoring system according to the Lugano Classification hematologic and extra-hematologic toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 50 and feasibility arbitrarily defined as 5 patients receiving 85 of the planned dose Noteworthy the cardiologic toxicity profile was established by using the echocardiography assessment of global systolic longitudinal myocardial strain GLS as well as left ventricular ejection fraction LVEF according to the guidelines of the Task Force for Cancer Treatments and Cardiovascular Toxicity of the European Society of Cardiology ESC
The schedule of study treatment is shown in detail in Table 1 The dosage of Myocet TM in the MVD scheme was well within the ceiling dose of 785 mgm 2 the median lifetime dose reported for NPLD at the onset of cardiotoxicity Patients were scheduled to receive six cycles of therapy with MVD which consisted of 1-day outpatient iv infusions of Myocet TM at a dose of 25 mgm 2 plus vinblastine 6 mgm 2 and dacarbazine 375 mgm 2 on days 1 and 14 of each course every 28 days for twelve administrations Planned cumulative dose-intensity of NPLD was 300 mgm 2
For those cases with initial large nodal mass defined as systemic adenopathy with the largest diameter 5 cm consolidation radiotherapy c-RT at 30 Gy was given after EoT PET assessments following the scheduled 6 MVD cycles on residual bulky area that is containing post-chemotherapy FDG-PET negative nodes of size 20 cm at CT scans as already reported
FDG-PET examinations were conducted at staging EoT and thereafter every 3-6 months FDG-PET results were reported according to the DS score using visual assessment followed by quantitative verification as already described Negative FDG-PET scans were defined as DS 3 score and positive FDG-PET scans were defined as DS 4 and 5 scores Supplemental data FDG- PET assessments All patients were scheduled to undergo a full cardiologic examination 2D echocardiography and speckle tracking echocardiography STE at baseline interim EoT and within six months from the end of all antineoplastic treatments
Clinical cardiologist experts in echocardiography analyzed each study for standard echocardiography and strain measurements
Physical examination and bone marrow biopsy were also performed at baseline and then at physicians discretion Routine blood laboratory test monitoring was performed before every cycle of chemotherapy for each patient
OS was defined as the time from the date of HL diagnosis to the date of last follow-up or death for any cause PFS was defined as the time from day 1 of MVD first dose to disease progressionrelapse event death from any cause event or last follow-up visit censoring All efficacy and safety evaluations were performed in patients who received at least one course of MVD Patients characteristics response rate toxicity and safety data were reported descriptively as number and percentage or as median and range Survival curves were estimated by the Kaplan-Meier method Cox regression analysis was used to estimate the hazard ratio HR and the 95 confidence interval CI for the treatment effect on OS and PFS The evaluated factors included age stratification years 60-69 vs 70-79 vs 80 B symptoms large nodal mass nodal andor extra-nodal sites involved stage IV and international prognostic score IPS risk group at baseline Differences between groups were tested by the log-rank test and student-T test The P value for statistical significance was set at 005 for all evaluations Statistical analysis was performed using R software version 41
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None