Non-Hodgkin's Lymphoma, Relapsed Clinical Trial
Official title:
Combination Chemotherapy Using Cisplatin, Gemcitabine, Ifosfamide, Etoposide, L-asparaginase and Dexamethasone (SIMPLE) for Newly Diagnosed and Relapsed/Refractory NK/T Cell Malignancies
NK malignancies consist of two different clinical entities, extranodal NK/T cell lymphoma and
aggressive NK leukaemia. Queen Mary Hospital (QMH) had started to use PIGLETS chemotherapy
for treatment of NK malignancies since 2013, with promising results. The study in QMH had
ended because of successful recruitment in the planned number of subjects.
When PIGLETS was used in extranodal NK/T cell lymphoma, patients with stage I/II lymphoma
have an overall response rate of nearly 90%, while patients with stage III/IV disease have an
overall response rate of around 60%. The figures are comparable to the SMILE chemotherapy
previously used. However, PIGLETS regimen carries much lower risk of nephrotoxicity when
compared with SMILE. It has since become a standard protocol in management of NK malignancies
in our institution.
PIGLETS chemotherapy carries two major problems:
1. the name PIGLETS may appear offensive to some religious populations. (e.g. Muslim)
2. significant nausea/vomiting was seen in previous studies, and these could at least be
partially alleviated with substance P antagonist aprepitant
Thus the investigators decided to start a study, renaming the original PIGLETS regimen into
SIMPLE chemotherapy, adding aprepitant as antiemetics and to recruit more patients for
evaluation of clinical efficacy. The results of SIMPLE chemotherapy will be compared to SMILE
in a non-inferiority trial setting.
Natural killer (NK)/T-cell malignancies comprise two related entities, extranodal NK/T cell
lymphoma and aggressive NK leukaemia. The disease occurs world-wide but Asian and South
American populations are particularly affected, NK/T cell malignancies carry poor prognosis,
the response rate is low with conventional CHOP (cyclophosphamide, doxorubicin, vincristine
and prednisolone) or CHOP-like regimen even for newly diagnosed disease. These regimens are
typically ineffective for relapsed disease.
In the last 10 years the investigators have employed two different regimen sequentially. The
former SMILE regimen (Dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide)
harness the combination of P-gp independent chemotherapy in management of NK/T cell
malignancies with great success. However, nephrotoxicity remained a major concern with the
use of this regimen. The SMILE regimen was later modified as PIGLETS regimen (cisplatin,
ifosfamide, gemcitabine, L-asparaginase, etoposide, dexamethasone) to reduce the risk of
nephrotoxicity while preserving the treatment efficacy. The study with the use of PIGLETS was
approved by IRB. The preliminary results of phase II clinical trial with PIGLETS at Queen
Mary Hospital resulted in an overall response rate (ORR) of 80% in newly diagnosed disease.
The recruitment was completed with previous PIGLETS phase II trial. The problems with the
PIGLETS regimen are:
1. The term 'PIGLETS' may appear to be offensive in some of the ethnicities/religions.
2. Significant nausea and vomiting, which may be delayed after completion of chemotherapy.
In addition, there is a need of further subject recruitment for comparison with SMILE therapy
for non-inferiority. In the current study, the regimen was renamed as 'SIMPLE' and aprepitant
(a substance P antagonist) was added in the regimen to reduce the incidence of nausea and
vomiting. The current study aims to compare SIMPLE to SMILE in a 'non-inferiority' design.
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