T-Cell LymphomaPhase 2NCT03021057
Pembrolizumab for T/NK-cell lymphomasNK-cell Lymphomas
A Phase 2 study testing pembrolizumab in people with T-Cell Lymphoma and NK-Cell Lymphoma, run by The University of Hong Kong at 1 site in Hong Kong.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- T-Cell Lymphoma, NK-Cell Lymphoma
- What is being tested?
- pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Dec 2016to Dec 2020
- Phase
- Phase 2
- 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
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age on day of signing informed consent.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) will be considered on a case-by-case basis.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Demonstrate adequate organ function , all screening labs should be performed within 10 days of treatment initiation.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has undergone prior allogeneic HSCT
- Has a known history of active TB (Bacillus Tuberculosis)
- Has hypersensitivity to pembrolizumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Show all 21Show fewer
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B virus or Hepatitis C virus infection.
- Has received a live vaccine within 30 days of planned start of study therapy.
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
The University of Hong Kong
Hong Kong
Eric Tse, MBBS, 85222553975, ewctse@hku.hk
Crosby Lu, MMedSc, 85222554361, khlu@hku.hk
About this study
Official title: PD-1 Blockade With Pembrolizumab in Relapsed/Refractory Mature T-cell and NK-cell Lymphomas
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.
Read the 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.
- Conditions
- T-Cell Lymphoma, NK-Cell Lymphoma
- Being tested
- pembrolizumab
- Medical subject headings
- Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pembrolizumabDrug
Also called Keytruda
200mg i.v. once every 3 weeks Number of Cycles: until progression or unacceptable toxicity develops
| Study group | Role | What they receive |
|---|---|---|
| pembrolizumab | Experimental | 200mg i.v. once every 3 weeks Number of Cycles: until progression or unacceptable toxicity develops Receives: Drug: pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission rate (CR)
Complete remission (CR) rate at 12 weeks and thereafter
Measured: 12 weeks
Secondary outcomes (4)
Overall response rate (ORR)
defined as the proportion of patients achieving CR or PR at 12 weeks and thereafter.
Measured: 12 weeks
Duration of response (DOR)
defined as the time from the first documented response (CR or PR) to the earliest relapse or progression
Measured: 2 years
Progression free survival (PFS)
defined as the time from the treatment initiation until the first documented disease progression or death from any cause
Measured: 2 years
Overall survival (OS)
defined as the time from the treatment initiation until death as a result of any cause
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 posted13 Jan 2017 (estimated)
- Study start1 Dec 2016
- Primary completionJun 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for T-Cell LymphomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Dr. Eric W.C. Tse, The University of Hong Kong
- Investigators
- Eric Tse, PhD(Cantab), Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03021057
- Sponsor's protocol ID
- HKU-MK-NKT01
- Status last verified
- Apr 2019
- First submitted
- 11 Jan 2017
- Last updated
- 17 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PD-1 Blockade With Pembrolizumab in Relapsed/Refractory Mature T-cell and NK-cell Lymphomas
- ClinicalTrials.gov ID
- NCT03021057
- Acronym / sponsor ID
- HKU-MK-NKT01
- Conditions
- T-Cell Lymphoma, NK-Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Dec 2016 (actual)
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 13 Jan 2017 (estimated)
- 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.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| pembrolizumab | Experimental | Drug: pembrolizumab200mg i.v. once every 3 weeks Number of Cycles: until progression or unacceptable toxicity develops |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age on day of signing informed consent.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) will be considered on a case-by-case basis.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Demonstrate adequate organ function , all screening labs should be performed within 10 days of treatment initiation.
Key exclusion criteria (21 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has undergone prior allogeneic HSCT
- Has a known history of active TB (Bacillus Tuberculosis)
- Has hypersensitivity to pembrolizumab or any of its excipients.
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 |
|---|---|---|
| pembrolizumabAlso: Keytruda200mg i.v. once every 3 weeks Number of Cycles: until progression or unacceptable toxicity develops | Drug | pembrolizumab |
Primary outcome
Complete remission rate (CR)
Time frame: 12 weeks
Complete remission (CR) rate at 12 weeks and thereafter
4 secondary outcomes
Overall response rate (ORR)
Time frame: 12 weeks
Duration of response (DOR)
Time frame: 2 years
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 17 Apr 2019.
Related trials for T-Cell Lymphoma
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Active, not recruitingObservational study
Multi-omics Profiling of Relapsed Extranodal Natural Killer (NK)/T-cell Lymphoma
Extranodal NK/T-cell Lymphoma, Nasal Type
RecruitingPhase 1/2
A Platform Trial Evaluating New Drugs or Combination in R/R Peripheral T-cell Lymphomas
Peripheral T Cells Lymphoma (PTCL), Follicular Helper T-Cell Lymphoma
Active, not recruitingPhase 2
Dosing of Brentuximab Vedotin for Mycosis Fungoides, Sezary Syndrome Patients
Mycosis Fungoides, Lymphomatoid Papulosis
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.
Eric Tse, PhD(Cantab) 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 2 study testing pembrolizumab in people with T-Cell Lymphoma and NK-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 8 inclusion and 21 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 17 Apr 2019. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Eric Tse, PhD(Cantab) (85222554361, ewctse@hku.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete remission rate (CR) (time frame: 12 weeks). 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 17 Apr 2019.