Ignite Creation Date:
2025-12-24 @ 6:42 PM
Ignite Modification Date:
2025-12-25 @ 4:12 PM
Study NCT ID:
NCT03021057
Status:
UNKNOWN
Last Update Posted:
2019-04-17
First Post:
2017-01-11
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Pembrolizumab for T/NK-cell lymphomasNK-cell Lymphomas
Sponsor:
The University of Hong Kong
Organization:
Study Overview
Official Title:
PD-1 Blockade With Pembrolizumab in Relapsed/Refractory Mature T-cell and NK-cell Lymphomas
Status:
UNKNOWN
Status Verified Date:
2019-04
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Conventional chemotherapeutic regimens designed for aggressive B-cell lymphomas are generally less effective when applied to mature T-cell or NK-cell lymphomas. The treatment outcome for relapsed or refractory disease is especially poor.
This is a single centre, prospective, non-randomized, open-label, phase II study to evaluate the efficacy of pembrolizumab in patients with relapsed or refractory mature T-cell or NK-cell lymphomas. Patients will receive pembrolizumab 200mg i.v. once every 3 weeks until disease progression or unacceptable toxicity.
A baseline radiological assessment by positron emission tomography / computed tomography (PET/CT) scan is obtained before commencement of treatment. Tumor response and progression are evaluated by physical examination, standard laboratory tests, and PET/CT scan according to standard criteria. Standard response criteria for non-Hodgkin lymphomas are used for assessment . PET/CT scan will be done at week 12, week 24, week 36 and every 18 weeks thereafter.
This is a single centre, prospective, non-randomized, open-label, phase II study to evaluate the efficacy of pembrolizumab in patients with relapsed or refractory mature T-cell or NK-cell lymphomas. Patients will receive pembrolizumab 200mg i.v. once every 3 weeks until disease progression or unacceptable toxicity.
A baseline radiological assessment by positron emission tomography / computed tomography (PET/CT) scan is obtained before commencement of treatment. Tumor response and progression are evaluated by physical examination, standard laboratory tests, and PET/CT scan according to standard criteria. Standard response criteria for non-Hodgkin lymphomas are used for assessment . PET/CT scan will be done at week 12, week 24, week 36 and every 18 weeks thereafter.
Detailed Description:
Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype against PD-1, designed to directly block its interaction with PD-L1 and PD-L2. KeytrudaTM (pembrolizumab) has recently been approved in the United Stated for the treatment of melanoma that is unresectable or metastatic, or has progressed following ipilumumab and, (if BRAF V600 mutation positive), a BRAF inhibitor.
Mature T-cell and nature killer (NK)-cell lymphomas are lymphoid malignancies that are derived from T-cell and NK-cell lineages. They are less prevalent than B-cell lymphomas. Interestingly, there are distinct geographic differences in their distribution and prevalence. Nodal lymphomas including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL) and cutaneous T-cell lymphomas (CTCL) predominate in Western populations, accounting for about 10% of all lymphomas. In Asian countries, however, extranodal NK/T-cell lymphoma, nasal type, is much more prevalent, constituting 10% of all lymphomas; with AITL, ALCL and PTCL-NOS accounting for another 10%. Epstein Barr virus (EBV) infection is found in all cases of extranodal NK/T-cell lymphomas, the majority of AITL, and a significant proportion of PTCL-NOS, implying that it plays an important pathogenetic role.
Conventional chemotherapeutic regimens designed for aggressive B-cell lymphomas are generally less effective when applied to mature T-cell or NK-cell lymphomas. The treatment outcome for relapsed or refractory disease is especially poor. In a recent retrospective analysis, the median overall survival (OS) and progression-free survival (PFS) in patients with disease relapse were found to be only 5.5 and 3.1 months respectively. The efficacy of newly approved agents such as pralatrexate and romidepsin for relapsed or refractory T-cell lymphomas is modest, with an average overall response rate (ORR) of around 20-30% only. Novel therapeutic approaches are therefore needed for this group of patients with dismal prognosis.
PD-1 blockade using anti-PD1 monoclonal antibody has been shown to be highly effective for relapsed/refractory classical Hodgkin lymphoma. Furthermore, clinical response has also been seen in relapsed T-cell lymphomas after treatment with anti-PD-1 antibody in phase I studies. In addition, previous reports have shown that EBV infection may enhance the expression of PD-L1 in tumour cells, and that some EBV-associated lymphomas such as NK/T-cell lymphoma express high level of PD-L1, suggesting that EBV-associated mature T-cell and NK-cell lymphomas may be more susceptible to PD-1 blockade.
Mature T-cell and nature killer (NK)-cell lymphomas are lymphoid malignancies that are derived from T-cell and NK-cell lineages. They are less prevalent than B-cell lymphomas. Interestingly, there are distinct geographic differences in their distribution and prevalence. Nodal lymphomas including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL) and cutaneous T-cell lymphomas (CTCL) predominate in Western populations, accounting for about 10% of all lymphomas. In Asian countries, however, extranodal NK/T-cell lymphoma, nasal type, is much more prevalent, constituting 10% of all lymphomas; with AITL, ALCL and PTCL-NOS accounting for another 10%. Epstein Barr virus (EBV) infection is found in all cases of extranodal NK/T-cell lymphomas, the majority of AITL, and a significant proportion of PTCL-NOS, implying that it plays an important pathogenetic role.
Conventional chemotherapeutic regimens designed for aggressive B-cell lymphomas are generally less effective when applied to mature T-cell or NK-cell lymphomas. The treatment outcome for relapsed or refractory disease is especially poor. In a recent retrospective analysis, the median overall survival (OS) and progression-free survival (PFS) in patients with disease relapse were found to be only 5.5 and 3.1 months respectively. The efficacy of newly approved agents such as pralatrexate and romidepsin for relapsed or refractory T-cell lymphomas is modest, with an average overall response rate (ORR) of around 20-30% only. Novel therapeutic approaches are therefore needed for this group of patients with dismal prognosis.
PD-1 blockade using anti-PD1 monoclonal antibody has been shown to be highly effective for relapsed/refractory classical Hodgkin lymphoma. Furthermore, clinical response has also been seen in relapsed T-cell lymphomas after treatment with anti-PD-1 antibody in phase I studies. In addition, previous reports have shown that EBV infection may enhance the expression of PD-L1 in tumour cells, and that some EBV-associated lymphomas such as NK/T-cell lymphoma express high level of PD-L1, suggesting that EBV-associated mature T-cell and NK-cell lymphomas may be more susceptible to PD-1 blockade.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: