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

NCT ID: NCT03071822

Last Updated: 2018-06-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-24
• Study Completion Date: 2022-02-28

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.

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:

1. The PIGLETS regimen had been in used since 2013, with the toxicities well known to the investigators

2. Typical side effects of chemotherapy would be anticipated, including cytopenia, alopecia, mucositis and emesis. These can all be managed with supportive therapy

3. 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.

Conditions

Peripheral T Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PIGLETs

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

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

PIGLETs

ifosfamide

Intervention Type: DRUG

PIGLETs

gemcitabine

Intervention Type: DRUG

PIGLETs

L-asparaginase

Intervention Type: DRUG

PIGLETs

etoposide

Intervention Type: DRUG

PIGLETs

dexamethasone

Intervention Type: DRUG

PIGLETs

Interventions

cisplatin

PIGLETs

Intervention Type: DRUG

ifosfamide

PIGLETs

Intervention Type: DRUG

gemcitabine

PIGLETs

Intervention Type: DRUG

L-asparaginase

PIGLETs

Intervention Type: DRUG

etoposide

PIGLETs

Intervention Type: DRUG

dexamethasone

PIGLETs

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients between the age of 18 - 80 years, with confirmed PTCLs

2. Adequate organ functions

3. ECOG performance status of <=2

4. No history of hypersensitivity to any of the components of the PIGLETS regimen

5. Informed consent obtained

Exclusion Criteria

1. Inadequate organ functions

2. ECOG performance status of >=3

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Professor Yok-lam Kwong

Chair Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yok Lam Kwong, MBBS

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

The University of Hong Kong

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Sau Yan Thomas Chan, MBBS

Role: CONTACT

thomas28@netvigator.com

852-22554361

Crosby Lu, BN

Role: CONTACT

khlu@hku.hk

852-22555161

Facility Contacts

King Hei Lu, MMedSc

Role: primary

khlu@hku.hk

852-22554361 ext. 1654

Zoe Chan, BNs

Role: backup

zoechan1@hku.hk

852-22551654

Other Identifiers

PTCL-001

Identifier Type: -

Identifier Source: org_study_id