Non-Hodgkin's Lymphoma, RelapsedPhase 3NCT03623087
SIMPLE Chemotherapy for NK Lymphoma/Leukaemia
A Phase 3 study testing Cisplatin, Gemcitabine and Etoposide (VP-16) in people with Non-Hodgkin's Lymphoma, Relapsed and Non-Hodgkin T-cell Lymphoma, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin's Lymphoma, Relapsed, Non-Hodgkin T-cell Lymphoma, Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type
- What is being tested?
- Cisplatin, Gemcitabine and Etoposide (VP-16)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Jul 2017to 30 Jun 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients age 18-80 with biopsy proven extranodal NK/T cell lymphoma, nasal type or aggressive NK leukaemia
- ECOG performance score <=2
Who cannot join
- Poor performance status with ECOG >=3
- Impairment of renal function (serum creatinine more than or equal to 200umol/L) not otherwise attributed to the tumour involvement.
- Impairment of liver function with liver parenchymal enzymes 5 times the upper limit of normal range, not otherwise attributed to tumour involvement.
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
The University of Hong Kong
Hong Kong
King Hei Lu, MMedSc, 852-22554361 ext. 1654, khlu@hku.hk
Zoe Chan, BNs, 852-22551654, zoechan1@hku.hk
About this study
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.
Read more
PIGLETS chemotherapy carries two major problems:
- the name PIGLETS may appear offensive to some religious populations. (e.g. Muslim)
- 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.
Read the detailed description
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:
- The term 'PIGLETS' may appear to be offensive in some of the ethnicities/religions.
- 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
- Non-Hodgkin's Lymphoma, Relapsed, Non-Hodgkin T-cell Lymphoma, Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type
- Being tested
- Cisplatin, Gemcitabine, Etoposide (VP-16), Ifosfamide, Dexamethasone
- Medical subject headings
- Lymphoma, Non-Hodgkin, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
SIMPLE
GemcitabineDrug
SIMPLE
Etoposide (VP-16)Drug
SIMPLE
IfosfamideDevice
SIMPLE
DexamethasoneDrug
SIMPLE
L-asparaginaseDrug
SIMPLE
| Study group | Role | What they receive |
|---|---|---|
| SIMPLE | Experimental | cisplatin, gemcitabine, ifosfamide, etoposide (VP-16), L-asparaginase, dexamethasone Receives: Drug: Cisplatin; Drug: Gemcitabine; Drug: Etoposide (VP-16); Device: Ifosfamide; Drug: Dexamethasone; Drug: L-asparaginase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy as measured by overall response rate measured at the time of best response.
Overall response rate (ORR) is defined as the proportion of patients with reduction in tumor burden of at least 50%.
Measured: 2 years
Secondary outcomes (3)
Adverse events and severe adverse events related to the treatment
Incidence of AE and SAE by severity grading as assessed according to CTCAE v4.03
Measured: 1 year
Progression-free survival (PFS)
PFS is defined as the time from enrolment to progression or death due to any cause. The distribution of PFS will be estimated using the method of Kaplan-Meier.
Measured: 2 years
Overall survival (OS)
OS is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2018
- Study start1 Jul 2017
- Primary completion14 Mar 2020 (estimated)
- Study completion30 Jun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin's Lymphoma, RelapsedStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Yok-lam Kwong, The University of Hong Kong
- Investigators
- Yok Lam Kwong, MBBS, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03623087
- Sponsor's protocol ID
- NK-002
- Status last verified
- Aug 2018
- First submitted
- 25 Jul 2018
- Last updated
- 14 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Chemotherapy Using Cisplatin, Gemcitabine, Ifosfamide, Etoposide, L-asparaginase and Dexamethasone (SIMPLE) for Newly Diagnosed and Relapsed/Refractory NK/T Cell Malignancies
- ClinicalTrials.gov ID
- NCT03623087
- Acronym / sponsor ID
- NK-002
- Conditions
- Non-Hodgkin's Lymphoma, Relapsed, Non-Hodgkin T-cell Lymphoma, Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 14 Mar 2020 (estimated)
- Study completion
- 30 Jun 2020 (estimated)
- First posted
- 9 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- the name PIGLETS may appear offensive to some religious populations. (e.g. Muslim)
- 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
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:
- The term 'PIGLETS' may appear to be offensive in some of the ethnicities/religions.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SIMPLE | Experimental | Drug: Cisplatin, Drug: Gemcitabine, Drug: Etoposide (VP-16), Device: Ifosfamide, Drug: Dexamethasone, Drug: L-asparaginasecisplatin, gemcitabine, ifosfamide, etoposide (VP-16), L-asparaginase, dexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult patients age 18-80 with biopsy proven extranodal NK/T cell lymphoma, nasal type or aggressive NK leukaemia
- ECOG performance score <=2
Key exclusion criteria (3 listed)
- Poor performance status with ECOG >=3
- Impairment of renal function (serum creatinine more than or equal to 200umol/L) not otherwise attributed to the tumour involvement.
- Impairment of liver function with liver parenchymal enzymes 5 times the upper limit of normal range, not otherwise attributed to tumour involvement.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CisplatinSIMPLE | Drug | SIMPLE |
| GemcitabineSIMPLE | Drug | SIMPLE |
| Etoposide (VP-16)SIMPLE | Drug | SIMPLE |
| IfosfamideSIMPLE | Device | SIMPLE |
| DexamethasoneSIMPLE | Drug | SIMPLE |
| L-asparaginaseSIMPLE | Drug | SIMPLE |
Primary outcome
Efficacy as measured by overall response rate measured at the time of best response.
Time frame: 2 years
Overall response rate (ORR) is defined as the proportion of patients with reduction in tumor burden of at least 50%.
3 secondary outcomes
Adverse events and severe adverse events related to the treatment
Time frame: 1 year
Progression-free survival (PFS)
Time frame: 2 years
Overall survival (OS)
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yok Lam Kwong, MBBS principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cisplatin, Gemcitabine and Etoposide (VP-16) in people with Non-Hodgkin's Lymphoma, Relapsed and Non-Hodgkin T-cell Lymphoma, run by The University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dr Thomas Chan, MBBS (852-22553456, thomas28@netvigator.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy as measured by overall response rate measured at the time of best response. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2018.