Combination Chemotherapy Including Cisplatin, Ifosfamide, Gemcitabine, L-asparaginase, Etoposide and Dexamethasone as Treatment of Newly Diagnosed and Relapsed/Refractory Peripheral T Cell Lymphomas

Sponsor

The University of Hong Kong (Other)

Overall Status

Unknown status

CT.gov ID

NCT03071822

Collaborator

(none)

Enrollment

Location

Arm

60.1

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The PIGLETS regimen was devised to replace the conventional SMILE regimen in management of extranodal NK/T cell lymphoma in our institution. It had been three years since the introduction of PIGLETS regimen in treatment of NK malignancies. The response rate is encouraging, with an overall response rate (ORR) of 90% in NK malignancies. Side effects are generally tolerable. The investigator therefore propose the use of PIGLETS on newly diagnosed or relapsed/refractory PTCLs.

Condition or Disease	Intervention/Treatment	Phase
Peripheral T Cell Lymphoma	Drug: cisplatin Drug: ifosfamide Drug: gemcitabine Drug: L-asparaginase Drug: etoposide Drug: dexamethasone	Phase 4

Detailed Description

Peripheral T cell lymphomas (PTCLs) are a group of heterogenous lymphoid malignancies derived from post-thymic mature T-lymphocytes. They are further classified according to their putative origin, immunophenotype, sites of involvement and clinical behaviour. Common subtypes include PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL). With the exception of ALCL, PTCLs behave aggressively and their response to chemotherapy is typically poor. CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisolone) borrowed from treatment of B-cell lymphoma is commonly used. However, there is no randomized controlled trial evaluating its efficacy. Moreover, despite the initial response of 40-70%, most patients suffer from disease relapse, giving rise to disappointing five year disease free survival (DFS) and overall survival (OS), typically in the range of 30% and 20%, respectively. As a result, there is not yet a standard agreed-on regimen for treatment of PTCLs in an upfront setting.

One of the possible mechanisms behind the intrinsic resistance to chemotherapy in PTCLs is the overexpression of multi-drug resistance (MDR) gene/P-glycoprotein (P-gp), which mediates active efflux of chemotherapeutic medications out of intracellular compartment. Regimens combining drugs which are independent of the P-gp pathway were proven to be successful in the management of PTCL, extranodal NK/T cell lymphoma, a lymphoma also expressing high level of MDR gene/P-glycoprotein. The PIGLETS regimen was devised to replace the conventional SMILE regimen in management of extranodal NK/T cell lymphoma in our institution. It had been three years since the introduction of PIGLETS regimen in treatment of NK malignancies. The response rate is encouraging, with an overall response rate (ORR) of 90% in NK malignancies. Side effects are generally tolerable. The investigator therefore propose the use of PIGLETS on newly diagnosed or relapsed/refractory PTCLs.

Expected toxicity:

The PIGLETS regimen had been in used since 2013, with the toxicities well known to the investigators
Typical side effects of chemotherapy would be anticipated, including cytopenia, alopecia, mucositis and emesis. These can all be managed with supportive therapy
Anaphylactic reaction to L-asparaginase may occur, but a small test dose will be given before formal administration to ensure the absence of allergy. Prophylactic antihistamine and glucocorticoids will also be given.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Patient will be given this combination of chemotherapy (cisplatin, ifosfamide, gemcitabine, L-asparaginase, etoposide and dexamethasone) for a total of 6 courses.Patient will be given this combination of chemotherapy (cisplatin, ifosfamide, gemcitabine, L-asparaginase, etoposide and dexamethasone) for a total of 6 courses.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Combination Chemotherapy Including Cisplatin, Ifosfamide, Gemcitabine, L-asparaginase, Etoposide and Dexamethasone (PIGLETS Regimen) as Treatment of Newly Diagnosed and Relapsed/Refractory Peripheral T Cell Lymphomas (PTCLs)

Actual Study Start Date :

Feb 24, 2017

Anticipated Primary Completion Date :

Jul 31, 2021

Anticipated Study Completion Date :

Feb 28, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PIGLETs Patient will be given this combination of chemotherapy (cisplatin, ifosfamide, gemcitabine, L-asparaginase, etoposide and dexamethasone) for a total of 6 courses	Drug: cisplatin PIGLETs Drug: ifosfamide PIGLETs Drug: gemcitabine PIGLETs Drug: L-asparaginase PIGLETs Drug: etoposide PIGLETs Drug: dexamethasone PIGLETs

Arm

Intervention/Treatment

Experimental: PIGLETs

Patient will be given this combination of chemotherapy (cisplatin, ifosfamide, gemcitabine, L-asparaginase, etoposide and dexamethasone) for a total of 6 courses

Drug: cisplatin

PIGLETs

Drug: ifosfamide

PIGLETs

Drug: gemcitabine

PIGLETs

Drug: L-asparaginase

PIGLETs

Drug: etoposide

PIGLETs

Drug: dexamethasone

PIGLETs

Outcome Measures

Primary Outcome Measures

Adverse events and severe adverse events [1 year]
Incidence of AE and SAE by severity grading as assessed according to CTCAE v4.03 Incidence of AE and SAE by severity grading as assessed according to CTCAE v4.03
Overall response rate (ORR) [3 months]
proportion of patients achieving CR or CRi or partial remission (PR)
Overall response rate (ORR) [6 months]
proportion of patients achieving CR or CRi or partial remission (PR)