Lymphoma, Extranodal NK-T-CellPhase 2NCT03439501
Avelumab in Relapsed or Refractory Extranodal Natural Killer/T-cell Lymphoma[AVENT STUDY]
A Phase 2 study testing avelumab in people with Lymphoma, Extranodal NK-T-Cell, run by Samsung Medical Center at 1 site in South Korea.
Trial summary
This study was conducted to evaluate the complete response rate of avelumab in patients with NK / T-cell lymphoma besides relapsed or refractory stage lymphoma. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Lymphoma, Extranodal NK-T-Cell
- What is being tested?
- avelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteSouth Korea
- Study dates
- 16 Jan 2018to 30 Mar 2022
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Historologically diagnosed ENKTL: The standards of WHO Classification 2016 for diagnosis of ENKTL satisfied.
- Became relapsed or refractory after at least one kind of treatment after initial diagnosis.
- If there is at least one measurable lesion.
- In case full-body activity (ECOG PS) is levels 0-2.
- In case of written consent to participation in clinical study: Must sign the subject consent form that states the sampling done at the time of diagnosis or relapse (must provide sample): 10 4um (at least 5) and biomarker (3~5 ml peripheral blood drawn during screening period, must provide sample) and that the subject has comprehended the purpose and the necessary procedures of clinical study with intention to participate in the clinical study (or signed by the subject's representative).
- If older than 19 years of age.
Show all 16Show fewer
- If the following hematological results are satisfied:
- Absolute neutrophil count is 1500/mm3 or greater regardless of growth factor supply.
- Platelet count is 100,000/mm3 or greater regardless of blood supply. (However, in cases of disease involvement, for example, platelet decrease due to bone marrow involvement or spleen enlargement, patients with a platelet count greater than 50000/mm3 may participate in this study.)
- Hemoglobin is 9.0 g/dL or greater.
- If the following biochemical results are satisfied:
- Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤ 2.5 x upper limit (ULN): If liver blood enzyme count is increasing due to a disease, such as the lymphoma's hepatic intrusion, may register up to ≤ 5 x ULN at investigator's discretion.
- If bilirubin is increasing due to the Gilbert Syndrome, total bilirubin ≤ 1.5 x ULN unless non-hepatic.
- Serum creatinine ≤ 2 x ULN or glomerular filtration rate (Cockroft Gault) ≥ 30 mL/min/1.73m2.
- Highly efficient birth control that meets the local regulations must be adopted for birth control of subjects that participate in the clinical study during or after the clinical study for women in fertility or sexually active men (in case of women in fertility, effective birth control must be used during the administration of study drug and for 1 month after that and men must use it during the administration of studyt drug and for 3 months after that).
- Women in fertility must show negative results at platelet (beta-chorionic gonadotropin) or pregnancy test by urine at screening.
Who cannot join
- If there is history of carcinomatous meningitis, symptomatic leptomeningeal diseases or evidence of secondary intrusion on the central nervous system based on CT or MRI scanning.
- In case there are other carcinomas besides the target disease or in case of anamnesis of other malicious tumers during the past 3 years from the start of clinical study: Excluding basal cell carcinoma and cervical intraepithelial neoplasia that are appropriately treated.
- If any toxicity from the previous chemotherapy has not recovered to grade 1 or lower at the time of screening; however hair loss and bone marrow inhibition are excluded and peripheral polyneuropathy may be registered at researcher's discretion if there is no risk of safety at Grade≤ 2.
- In case of major operation within 4 weeks from registration for the clinical study or failure to recover from a major complication of such operation.
- If using immunosuppressant drugs at the time of registration for the clinical study: Excluding local steroid injections such as nasal or inhalated steroid, steroid ointment, and injections in articular cavities. In case of full-body steroid administration, 10 mg or smaller prednisolonum a day is permissible (If adrenal insufficiency is necessary to maintain a dose of prednisolone 10 mg or more, it is acceptable according to the investigator's judgment) and steroid injections used for pre-treatment before CT or other examination are also permitted.
- In case of uncontrolled or symptomatic arrhythmia, congestive heart failure, myocardial infarction, cerebral infarction, or other clinically significant cardiovascular diseases or Class 3 (Moderate) or Class 4 (Severe) cardiac diseases functionally classified by New York Heart Association within 6 months of screening.
Show all 19Show fewer
- In case of history of serious hypersensitivity against the study drug used for this study or its substances including serious hypersensitivity against monoclonal antibody (NCI CTCAE v4.03 Grade ≥ 3).
- In case of known history of human immunodeficiency virus (HIV), active type C hepatitis virus, or active type B hepatitis virus (However, in the case of healthy carriers who did not require asymptomatic treatment, if the antiviral drug can be taken, it can be registered by the judgment of the investigator. In this case, the HBV DNA test should be monitored periodically through division of gastroenterology) or uncontrolled active full-body infection that requires intravenous (IV) antibiotics.
- In case of life-threatening diseases, medical conditions, or respiratory failure that may threaten the safety of subjects or put the results of clinical study in danger.
- In case of homogeneous hematopoietic stem cell transplant.
- In case of active autoimmune disease that may affect the administration of study drug; excluding type 1diabetes, psoriasis, vitiligo, hyperthyroidism, or hypothyroidism that does not require immunosuppressant.
- If the candidate cannot comprehend the clinical study or comply with the rules of clinical study including an active attempt to commit suicide or hurt oneself recently or in the past and other severe acute or chronic diseases such as immunocolitis, ulcerative colitis, immunopneumonia, pulmonary fibrosis, or mental conditions; or if determined by investigator that participation in the study is inappropriate due to any risk of participation or treatment in the study that may increase due to adverse effects or the interpretation of study results that may be hindered.
- If candidate is pregnant or breast-feeding at the time of screening.
- In case of a major operation or live attenuated vaccine within 4 weeks of registration for the clinical study.
- In case of the following hepatic diseases:
- Chronic hepatitis or liver cirrhosis related to type B or type C hepatitis.
- Positive reaction for surface antigen of type B hepatitis without symptoms. (However, in the case of healthy carriers who did not require asymptomatic treatment, if the antiviral drug can be taken, it can be registered by the judgment of the investigator. In this case, the HBV DNA test should be monitored periodically through division of gastroenterology): Positive reaction to RNA of type C hepatitis without symptoms.
- Previously exposed to PD-1 / PD-L1 inhibitor
- Use of other anticancer treatment or other study drugs within 4 weeks of registration for the clinical study.
Trial locations and contacts
1 site in 1 country.
South Korea1 site
81, Irwon-ro, Gangnam-gu, Seoul, Republic of Korea
Seoul, 06351
About this study
Official title: A Phase II Study of Avelumab in Relapsed or Refractory Extranodal Natural Killer/T-cell Lymphoma
This study was conducted to evaluate the complete response rate of avelumab in patients with NK / T-cell lymphoma besides relapsed or refractory stage lymphoma.
Read the detailed description
Extranodal natural killer/T-cell lymphoma (ENKTL) generally has poorer prognosis than other lymphomas because the majority of patients are present as advanced disease and show poor response to treatment.
In particular, treatment of relapsed or refractory stage ENKTL is very poor and there is no standard treatment.
ENKTL is entirely infected with Epstein-Barr virus (EBV) and the prevalence of this disease is closely related to EBV.
Therefore, the biological properties of ENKTL may be affected by EBV-related protein and LMP1 may induce activation of molecules in various sub-channels, such as PI3K/Akt and NF-kB, and affect the aggressiveness of lymphoma.
As an increase in PDL1 has been reported recently among the major roles of LMP1, the role of Immuno-oncology drug targeting PDL1 among ENKTL is expected.
Therefore, Avelumab that inhibits PDL1 may effectively treat NK/T-cell lymphoma besides relapsed or refractory stage lymphoma.
- Conditions
- Lymphoma, Extranodal NK-T-Cell
- Being tested
- avelumab
- Medical subject headings
- Lymphoma, Extranodal NK-T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
avelumabDrug
- Study drug: Avelumab (PD-L1 inhibitor; MSB0010718C)
- Dosage: 10 mg per body weight (kg) of a subject every two weeks
- One cycle consists of two injection of avelumab (28 days).
- The treatment cycle will be repeated until progression of disease or unacceptable toxicity and dose adjustments are permitted for patients who are unable to tolerate the side effects of drugs within each cycle.
| Study group | Role | What they receive |
|---|---|---|
| avelumab | Other | * 1 Cycle: 10mg/kg Avelumab administered via IV every 2 weeks (1st, 15th)
* Interval of 1 cycle: 28 days ③ Administration schedule: Repeated until disease progression or unacceptable toxicity and dose adjustments may be permitted based on the toxicity that occurs every cycle. Receives: Drug: avelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The rate of response of avelumab.
To assess the efficacy of disease control including complete response (CR), partial response (PR) and stable disease (SD)
Measured: From date of enrollment until the date first documented disease progression or unacceptable toxicity, whichever came first, assessed up to 48 months
Secondary outcomes (3)
Progression-free survival
It is a measure of the period of survival without disease progression
Measured: the time between the date of treatment start and the date of death due to any cause or date of disease progression..assessed up to 48 months
Overall survival (OS)
It measures the time from start of treatment to death.
Measured: Time between the start of treatment and the date of death.assessed up to 48 months
Toxicity Profile
Clinical and laboratory toxicity/symptomatology will be graded based on the NCIC CTG v4.03. Adverse events not reported in NCIC CTG will be categorized into mild, moderate, severe, and fatal and further classified to CTCAE Grades 1-4.
Measured: from the date of informed consent signature to 30 days after last drug administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2018
- Study start16 Jan 2018
- Primary completion30 Jan 2022 (estimated)
- Study completion30 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, Extranodal NK-T-CellStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe 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
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Principal investigator, Won Seog Kim, Samsung Medical Center
- Investigators
- Wonseog Kim, M.D, Principal investigator, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03439501
- Sponsor's protocol ID
- 2017-05-046
- Other IDs
- MS100070_0018
- Status last verified
- Sep 2021
- First submitted
- 17 Jan 2018
- Last updated
- 24 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kim SJ, Lim JQ, Laurensia Y, Cho J, Yoon SE, Lee JY, Ryu KJ, Ko YH, Koh Y, Cho D, Lim ST, Enemark MB, D'Amore F, Bjerre M, Ong CK, Kim WS. Avelumab for the treatment of relapsed or refractory extranodal NK/T-cell lymphoma: an open-label phase 2 study. Blood. 2020 Dec 10;136(24):2754-2763. doi: 10.1182/blood.2020007247.
PubMed 32766875
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Avelumab in Relapsed or Refractory Extranodal Natural Killer/T-cell Lymphoma
- ClinicalTrials.gov ID
- NCT03439501
- Acronym / sponsor ID
- 2017-05-046
- Conditions
- Lymphoma, Extranodal NK-T-Cell
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- 16 Jan 2018 (actual)
- Primary completion
- 30 Jan 2022 (estimated)
- Study completion
- 30 Mar 2022 (estimated)
- First posted
- 20 Feb 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.
This study was conducted to evaluate the complete response rate of avelumab in patients with NK / T-cell lymphoma besides relapsed or refractory stage lymphoma.
Detailed description
Extranodal natural killer/T-cell lymphoma (ENKTL) generally has poorer prognosis than other lymphomas because the majority of patients are present as advanced disease and show poor response to treatment.
In particular, treatment of relapsed or refractory stage ENKTL is very poor and there is no standard treatment.
ENKTL is entirely infected with Epstein-Barr virus (EBV) and the prevalence of this disease is closely related to EBV.
Therefore, the biological properties of ENKTL may be affected by EBV-related protein and LMP1 may induce activation of molecules in various sub-channels, such as PI3K/Akt and NF-kB, and affect the aggressiveness of lymphoma.
As an increase in PDL1 has been reported recently among the major roles of LMP1, the role of Immuno-oncology drug targeting PDL1 among ENKTL is expected.
Therefore, Avelumab that inhibits PDL1 may effectively treat NK/T-cell lymphoma besides relapsed or refractory stage lymphoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| avelumab | Other | Drug: avelumab* 1 Cycle: 10mg/kg Avelumab administered via IV every 2 weeks (1st, 15th) * Interval of 1 cycle: 28 days ③ Administration schedule: Repeated until disease progression or unacceptable toxicity and dose adjustments may be permitted based on the toxicity that occurs every cycle. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Historologically diagnosed ENKTL: The standards of WHO Classification 2016 for diagnosis of ENKTL satisfied.
- Became relapsed or refractory after at least one kind of treatment after initial diagnosis.
- If there is at least one measurable lesion.
- In case full-body activity (ECOG PS) is levels 0-2.
- In case of written consent to participation in clinical study: Must sign the subject consent form that states the sampling done at the time of diagnosis or relapse (must provide sample): 10 4um (at least 5) and biomarker (3~5 ml peripheral blood drawn during screening period, must provide sample) and that the subject has comprehended the purpose and the necessary procedures of clinical study with intention to participate in the clinical study (or signed by the subject's representative).
Key exclusion criteria (19 listed)
- If there is history of carcinomatous meningitis, symptomatic leptomeningeal diseases or evidence of secondary intrusion on the central nervous system based on CT or MRI scanning.
- In case there are other carcinomas besides the target disease or in case of anamnesis of other malicious tumers during the past 3 years from the start of clinical study: Excluding basal cell carcinoma and cervical intraepithelial neoplasia that are appropriately treated.
- If any toxicity from the previous chemotherapy has not recovered to grade 1 or lower at the time of screening; however hair loss and bone marrow inhibition are excluded and peripheral polyneuropathy may be registered at researcher's discretion if there is no risk of safety at Grade≤ 2.
- In case of major operation within 4 weeks from registration for the clinical study or failure to recover from a major complication of such operation.
- If using immunosuppressant drugs at the time of registration for the clinical study: Excluding local steroid injections such as nasal or inhalated steroid, steroid ointment, and injections in articular cavities. In case of full-body steroid administration, 10 mg or smaller prednisolonum a day is permissible (If adrenal insufficiency is necessary to maintain a dose of prednisolone 10 mg or more, it is acceptable according to the investigator's judgment) and steroid injections used for pre-treatment before CT or other examination are also permitted.
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 |
|---|---|---|
| avelumab* Study drug: Avelumab (PD-L1 inhibitor; MSB0010718C) * Dosage: 10 mg per body weight (kg) of a subject every two weeks * One cycle consists of two injection of avelumab (28 days). * The treatment cycle will be repeated until progression of disease or unacceptable toxicity and dose adjustments are permitted for patients who are unable to tolerate the side effects of drugs within each cycle. | Drug | avelumab |
Primary outcome
The rate of response of avelumab.
Time frame: From date of enrollment until the date first documented disease progression or unacceptable toxicity, whichever came first, assessed up to 48 months
To assess the efficacy of disease control including complete response (CR), partial response (PR) and stable disease (SD)
3 secondary outcomes
Progression-free survival
Time frame: the time between the date of treatment start and the date of death due to any cause or date of disease progression..assessed up to 48 months
Overall survival (OS)
Time frame: Time between the start of treatment and the date of death.assessed up to 48 months
Toxicity Profile
Time frame: from the date of informed consent signature to 30 days after last drug administration.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2021.
- Derived from this study: PubMed 32766875Kim SJ, Lim JQ, Laurensia Y, Cho J, Yoon SE, Lee JY, Ryu KJ, Ko YH, Koh Y, Cho D, Lim ST, Enemark MB, D'Amore F, Bjerre M, Ong CK, Kim WS. Avelumab for the treatment of relapsed or refractory extranodal NK/T-cell lymphoma: an open-label phase 2 study. Blood. 2020 Dec 10;136(24):2754-2763. doi: 10.1182/blood.2020007247.
- Individual participant dataSharing planned: No
Related trials for Lymphoma, Extranodal NK-T-Cell
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia
Active, not recruitingObservational study
Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia
Active, not recruitingPhase 2
Study of Pembrolizumab in Patients With Early-Stage NK/T-cell Lymphoma, Nasal Type
NK/T-Cell Lymphoma of Nasal Cavity (Diagnosis), NK/T-Cell Lymphoma of Nasopharynx (Diagnosis)
Active, not recruitingPhase 1/2
A Study to Assess the Safety, Tolerability, Efficacy, and Drug Levels of BMS-986369 (Golcadomide) in Participants With Relapsed or Refractory T-cell Lymphomas in Japan (GOLSEEK-3)
Relapsed or Refractory T-cell Lymphomas
Active, not recruitingPhase 1
Allogeneic CD30.CAR-EBVSTs in Patients With Relapsed or Refractory CD30-Positive Lymphomas
Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type, Classical Hodgkin Lymphoma
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.
Wonseog Kim, M.D principal investigator
Samsung Medical Center
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 avelumab in people with Lymphoma, Extranodal NK-T-Cell, run by Samsung Medical Center at 1 site in South Korea.
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 16 inclusion and 19 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 24 Sep 2021. 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 South Korea. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The rate of response of avelumab. (time frame: From date of enrollment until the date first documented disease progression or unacceptable toxicity, whichever came first, assessed up to 48 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03439501, which also lists 1 linked publication.
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 24 Sep 2021.