SIMPLE Chemotherapy for NK Lymphoma/Leukaemia

NCT ID: NCT03623087

Last Updated: 2018-08-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-01

Study Completion Date

2020-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non-Hodgkin's Lymphoma, Relapsed Non-Hodgkin T-cell Lymphoma Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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SIMPLE

cisplatin, gemcitabine, ifosfamide, etoposide (VP-16), L-asparaginase, dexamethasone

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

SIMPLE

Gemcitabine

Intervention Type DRUG

SIMPLE

Etoposide (VP-16)

Intervention Type DRUG

SIMPLE

Ifosfamide

Intervention Type DEVICE

SIMPLE

Dexamethasone

Intervention Type DRUG

SIMPLE

L-asparaginase

Intervention Type DRUG

SIMPLE

Interventions

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Cisplatin

SIMPLE

Intervention Type DRUG

Gemcitabine

SIMPLE

Intervention Type DRUG

Etoposide (VP-16)

SIMPLE

Intervention Type DRUG

Ifosfamide

SIMPLE

Intervention Type DEVICE

Dexamethasone

SIMPLE

Intervention Type DRUG

L-asparaginase

SIMPLE

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Adult patients age 18-80 with biopsy proven extranodal NK/T cell lymphoma, nasal type or aggressive NK leukaemia
2. ECOG performance score \<=2

Exclusion Criteria

1. Poor performance status with ECOG \>=3
2. Impairment of renal function (serum creatinine more than or equal to 200umol/L) not otherwise attributed to the tumour involvement.
3. Impairment of liver function with liver parenchymal enzymes 5 times the upper limit of normal range, not otherwise attributed to tumour involvement.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The University of Hong Kong

OTHER

Sponsor Role lead

Responsible Party

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Professor Yok-lam Kwong

Chair Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yok Lam Kwong, MBBS

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

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The University of Hong Kong

Hong Kong, , Hong Kong

Site Status RECRUITING

Countries

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Hong Kong

Central Contacts

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Dr Thomas Chan, MBBS

Role: CONTACT

852-22553456

Crosby Lu, MMedSc

Role: CONTACT

852-22551654

Facility Contacts

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King Hei Lu, MMedSc

Role: primary

852-22554361 ext. 1654

Zoe Chan, BNs

Role: backup

852-22551654

Other Identifiers

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NK-002

Identifier Type: -

Identifier Source: org_study_id

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