Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06235047 |
| Other study ID # |
FED-HL-MVD |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2013 |
| Est. completion date |
January 8, 2024 |
Study information
| Verified date |
January 2024 |
| Source |
Federico II University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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
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, i.e. Adriamycin, Bleomycin, Vinblastine, Dacarbazine) is a
therapeutic option for elderly/unfit 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-PET/CT 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, i.e., 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 5.0), 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 mg/m 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 i.v. infusions of Myocet TM at a dose of
25 mg/m 2 , plus vinblastine 6 mg/m 2 , and dacarbazine 375 mg/m 2 on days 1 and 14 of each
course every 28 days, for twelve administrations. Planned cumulative dose-intensity of NPLD
was 300 mg/m 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 ≥2.0 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
physician's 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
progression/relapse (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 and/or 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 0.05 for all evaluations. Statistical analysis was performed using R software (version
4.1).
