Immune Checkpoint InhibitorPhase 2NCT04414969
Anti-PD-1 Antibody Combined With Peg-Asparaginase and Chidamide for the Early Stage of NK/T Cell Lymphoma
A Phase 2 study testing Anti-PD-1 antibody+Peg-Asparaginase+Chidamide in people with Immune Checkpoint Inhibitor and Chemotherapy Effect, run by Hunan Cancer Hospital at 1 site in China.
Trial summary
This prospective pilot study to evaluate the efficacy and safety of the anti-PD-1 antibody combine with Peg-asparaginase and Chidamide regimen for stage IE and IIE ENKTL. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Immune Checkpoint Inhibitor, Chemotherapy Effect, Epigenetic Disorder
- What is being tested?
- Anti-PD-1 antibody+Peg-Asparaginase+Chidamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteChina
- Study dates
- 26 Jun 2020to 1 Jul 2025
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed, previously untreated ENKTL with stage I/II (for stage I, the patients should have one or more of the following risk factors: ①Extensive local invasion and or bone destruction: invasion of the inner orbital wall or bottom wall, orbital apex, orbital contents, maxillary sinus, sphenoid sinus, frontal sinus or ethmoid sinus invasion, hard palate, ethmoid plate, nasopharynx, slope bone is invaded. ②Skin invasion: nose and or cheek skin invasion; ③Waldeyer's ring invasion; ④LDH>upper limit of normal; ⑤EBV-DNA > upper limit of normal; ⑥B symptoms);
- Age range from 18 to 75 years;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- At least one evaluable or measurable lesion complying with Lugano 2014 Standard (evaluable lesion: the examination show increased uptake of lymph nodes or extranodal areas (higher than that of the liver) by 18F-Fluorodeoxyglucose/Positron Emission Tomography (18FDG/PET) and the PET and/or Computed Tomography (CT) features coincide with lymphoma characteristics; measurable lesion: nodal lesions were longer than 15 mm or extranodal lesions were longer than 10 mm, and accompanied by increased 18FDG uptake). Increased liver or spleen diffuse 18FDG uptake without measurable lesions should be excluded.
- Adequate haematologic function (haemoglobin ≥90 g/l, absolute neutrophil count ≥ 1500/ml, platelets ≥ 80×10e9/l),
- Adequate hepatic function (total serum bilirubin ≤ 1.5 times the upper limit of normal, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 times the upper limit of normal),
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- Hepatitis B virus carriers should have HBV-DNA <10e4 copies and should use antiviral drugs.
- Adequate renal function (serum creatinine ≤ 1.5 mg/dl, creatinine clearance ≥ 50 ml/min);
- Normal coagulation function and electrocardiogram results.
- No previous anti-cancer treatment including chemotherapy, radiotherapy, immunotherapy, biological therapy, glucocorticoids therapy for lymphoma.
- Willingness to provide written informed consent.
Who cannot join
- History of other malignancy within the past 5 years (except for basal cell carcinoma of the skin and carcinoma in situ of the cervix)
- With clinically diagnosed hemophagocytic syndrome (HPS); or aggressive NK cell leukemia; or central nervous system invasion;
- Previous treatments with immune checkpoint inhibitor, including nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, ipilimumab, sintilimab, etc.
- Previous treatments with HDAC inhibitor, including Chidamide, romidepsin, panobinostat, belinostat, etc.
- Patients allergic of any of drug in this regimen;
- Pregnant or lactating women
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- Participated in other clinical trials within the 4 weeks prior to enrollment;
- History of severe hemorrhage, or any bleeding events with a severe grade of 3 or more in CTCAE 5.0 within 4 weeks prior to enrollment
- Blood pressure unable to be controlled ideally with single antihypertensive drug therapy (Systolic blood pressure > 140 mmHg, Diastolic Blood Pressure > 90 mmHg); Clinically significant cardiovascular disease (e.g. activity) including history of CVA (within 6 months), myocardial infarction (within 6 months), unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure; serious cardiac arrhythmia beyond drug control or potentially affecting experimental therapy.
- The subject is being treated with immunosuppressive agents, glucocorticoids （systemic or absorbable local using）for immunosuppression purposes (dose> 10 mg / day prednisone or other therapeutic glucocorticoids) within two weeks before enrollment the study.
- Abnormal coagulation or bleeding tendency (It must be satisfied that INR is under normal range without anticoagulant within 14 days prior to signing informed consent); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues; on the premise that the international standardized ratio of prothrombin time (INR) is less than 1.5, small doses of warfarin (1 mg po, qd) or aspirin (no more than 100 mg qd) are allowed for preventive purposes.
- Arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (venous thrombosis caused by intravenous catheterization due to precancerous chemotherapy is excluded if it has been cured judged by the researchers) and pulmonary embolism.
- Suffered major surgery within 42 days prior to enrollment;
- Have an active autoimmune disease that requires systemic treatment within the past two years.
- Severe or uncontrolled infections, except fever associated with lymphoma B symptoms.
- History of psychotropic drug abuse and unable to get rid of or with mental disorders;
- History of immunodeficiency, including HIV positive testing, or other acquired, congenital immunodeficiency disorders, or organ transplantation history;
- Patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Hunan Cancer Hospital
Changsha, Hunan, 410013
Hui Zhou, MD., 8673189762281, Zhouhui@hnca.org.cn
Yajun Li, MD., 8673189762281, liyajun@hnca.org.cn
About this study
Official title: Anti-PD-1 Antibody, Peg-Asparaginase, Chidamide Combined With Radiotherapy for the First-line Treatment of Patients With Stage I/II Extranodal Natural Killer/T Cell Lymphoma, Nasal Type (ENKTL): An Open-label, Multicenter, Phase II Trial
This prospective pilot study to evaluate the efficacy and safety of the anti-PD-1 antibody combine with Peg-asparaginase and Chidamide regimen for stage IE and IIE ENKTL.
Read the detailed description
Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive subtype of non-Hodgkin's lymphoma and shows extremely poor survival. Several retrospective studies and randomized prospective phase 2 studies have shown that Peg-aspargase based chemotherapy regimens achieved a promising efficacy in the first line treatment of ENKTL. However, about one third of patients will relapse or become refractory after Peg-aspargase-based chemotherapy followed by radiotherapy, and some patients cannot tolerate the toxicities caused by chemotherapy. Anti-PD-1/PD-L1 antibodies and Chidamide are active drugs for the treatment of relapsed/refractory ENKTL. However, there is no prospective study to evaluate the efficacy and safety of anti-PD-1 antibody combine with Peg-asparaginase and Chidamide in the newly diagnosed early stage ENKTL. This prospective pilot study to evaluate the efficacy and safety of the anti-PD-1 antibody combine with Peg-asparaginase and Chidamide regimen for stage IE and IIE ENKTL.
- Conditions
- Immune Checkpoint Inhibitor, Chemotherapy Effect, Epigenetic Disorder, NK/T-cell Lymphoma of Nasal Cavity
- Being tested
- Anti-PD-1 antibody+Peg-Asparaginase+Chidamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-PD-1 antibody+Peg-Asparaginase+ChidamideDrug
Also called Anti-PD-1 antibody；Peg-Asparaginase；Chidamide
Anti-PD-1 antibody 200mg ivdrip d1, PEG-ASP 2500U/m2 im d1, Chidamide, 30mg, po, on d1，d5，d8，d12，d15，d19. The regimen was repeated every 3 weeks for 4 cycles followed by involved-field radiotherapy after got CR and PR (patients with efficacy of SD and PD withdrew from the study). Intensity-modulated radiation treatment was done by linear accelerator at 2.0 grays (Gy) per daily fraction with 5-6 weeks. The involved- field radiation (IFRT) dose was 54-56 Gy. During the radiotherapy, the anti-PD-1 antibody is administrated (200mg ivdrip, every 3 weeks) for 2 cycles. After the completion of radiotherapy, the subsequent 2 cycles of anti-PD-1 antibody + Peg-Asparaginase + Chidamide are administrated. After the end of all the above induction treatments , anti-PD-1 antibody (200mg ivdrip, every 3 weeks for up to 9 cycles) is given as maintenance therapy for 6 months (the total cycles of anti-PD-1 antibody is 17）.
| Study group | Role | What they receive |
|---|---|---|
| Anti-PD-1 antibody+Peg-Asparaginase+Chidamide | Experimental | Anti-PD-1 antibody 200mg ivdrip d1; PEG-ASP 2500U/m2 im d1; Chidamide, 30mg, PO, on d1，d5，d8，d12，d15，d19; repeat every 3 weeks. Receives: Drug: Anti-PD-1 antibody+Peg-Asparaginase+Chidamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
complete remission rate + partial remission rate
Measured: 12 weeks after the initiation of the treatment
Complete remission rate
complete remission rate
Measured: 12 weeks after the initiation of the treatment
Secondary outcomes (3)
Progression Free Survival (PFS)
Time from the date of enrollment to date of disease progression, or death of any cause, or date of lost follow-up, whichever comes first, otherwise subject data were censored at time last known disease free.
Measured: Up to three years after the start of the study
Overall Survival (OS)
Time from the date of enrollment to date of death from any cause, or date of lost follow-up, whichever comes first, and otherwise censored at time last known alive.
Measured: Up to three years after the start of the study
Safety issue
All the adverse events of the patients related will be assessed and graded by NCI CTCAE v 5.0
Measured: Up to one year after the end of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2020
- Study start26 Jun 2020
- Primary completion1 Jul 2022 (estimated)
- Study completion1 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immune Checkpoint InhibitorStudies of the same condition, open and under way.
- 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
- Model description
- An Open-label, multicenter, single group, phase II trial,
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hunan Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ya-Jun Li, Hunan Cancer Hospital
- Investigators
- Hui Zhou, M.D., Principal investigator, Department of Lymphoma and Hematology, Hunan Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04414969
- Sponsor's protocol ID
- HNCH-NKT-2020
- Status last verified
- Jul 2020
- First submitted
- 31 May 2020
- Last updated
- 7 Jul 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-PD-1 Antibody, Peg-Asparaginase, Chidamide Combined With Radiotherapy for the First-line Treatment of Patients With Stage I/II Extranodal Natural Killer/T Cell Lymphoma, Nasal Type (ENKTL): An Open-label, Multicenter, Phase II Trial
- ClinicalTrials.gov ID
- NCT04414969
- Acronym / sponsor ID
- HNCH-NKT-2020
- Conditions
- Immune Checkpoint Inhibitor, Chemotherapy Effect, Epigenetic Disorder, NK/T-cell Lymphoma of Nasal Cavity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Hunan Cancer HospitalUniversity, hospital or other
- Study start
- 26 Jun 2020 (actual)
- Primary completion
- 1 Jul 2022 (estimated)
- Study completion
- 1 Jul 2025 (estimated)
- First posted
- 4 Jun 2020 (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 prospective pilot study to evaluate the efficacy and safety of the anti-PD-1 antibody combine with Peg-asparaginase and Chidamide regimen for stage IE and IIE ENKTL.
Detailed description
Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive subtype of non-Hodgkin's lymphoma and shows extremely poor survival. Several retrospective studies and randomized prospective phase 2 studies have shown that Peg-aspargase based chemotherapy regimens achieved a promising efficacy in the first line treatment of ENKTL. However, about one third of patients will relapse or become refractory after Peg-aspargase-based chemotherapy followed by radiotherapy, and some patients cannot tolerate the toxicities caused by chemotherapy. Anti-PD-1/PD-L1 antibodies and Chidamide are active drugs for the treatment of relapsed/refractory ENKTL. However, there is no prospective study to evaluate the efficacy and safety of anti-PD-1 antibody combine with Peg-asparaginase and Chidamide in the newly diagnosed early stage ENKTL. This prospective pilot study to evaluate the efficacy and safety of the anti-PD-1 antibody combine with Peg-asparaginase and Chidamide regimen for stage IE and IIE ENKTL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- An Open-label, multicenter, single group, phase II trial,
| Arm | Type | Receives |
|---|---|---|
| Anti-PD-1 antibody+Peg-Asparaginase+Chidamide | Experimental | Drug: Anti-PD-1 antibody+Peg-Asparaginase+ChidamideAnti-PD-1 antibody 200mg ivdrip d1; PEG-ASP 2500U/m2 im d1; Chidamide, 30mg, PO, on d1，d5，d8，d12，d15，d19; repeat every 3 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Pathologically confirmed, previously untreated ENKTL with stage I/II (for stage I, the patients should have one or more of the following risk factors: ①Extensive local invasion and or bone destruction: invasion of the inner orbital wall or bottom wall, orbital apex, orbital contents, maxillary sinus, sphenoid sinus, frontal sinus or ethmoid sinus invasion, hard palate, ethmoid plate, nasopharynx, slope bone is invaded. ②Skin invasion: nose and or cheek skin invasion; ③Waldeyer's ring invasion; ④LDH>upper limit of normal; ⑤EBV-DNA > upper limit of normal; ⑥B symptoms);
- Age range from 18 to 75 years;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- At least one evaluable or measurable lesion complying with Lugano 2014 Standard (evaluable lesion: the examination show increased uptake of lymph nodes or extranodal areas (higher than that of the liver) by 18F-Fluorodeoxyglucose/Positron Emission Tomography (18FDG/PET) and the PET and/or Computed Tomography (CT) features coincide with lymphoma characteristics; measurable lesion: nodal lesions were longer than 15 mm or extranodal lesions were longer than 10 mm, and accompanied by increased 18FDG uptake). Increased liver or spleen diffuse 18FDG uptake without measurable lesions should be excluded.
- Adequate haematologic function (haemoglobin ≥90 g/l, absolute neutrophil count ≥ 1500/ml, platelets ≥ 80×10e9/l),
Key exclusion criteria (18 listed)
- History of other malignancy within the past 5 years (except for basal cell carcinoma of the skin and carcinoma in situ of the cervix)
- With clinically diagnosed hemophagocytic syndrome (HPS); or aggressive NK cell leukemia; or central nervous system invasion;
- Previous treatments with immune checkpoint inhibitor, including nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, ipilimumab, sintilimab, etc.
- Previous treatments with HDAC inhibitor, including Chidamide, romidepsin, panobinostat, belinostat, etc.
- Patients allergic of any of drug in this regimen;
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 |
|---|---|---|
| Anti-PD-1 antibody+Peg-Asparaginase+ChidamideAlso: Anti-PD-1 antibody；Peg-Asparaginase；ChidamideAnti-PD-1 antibody 200mg ivdrip d1, PEG-ASP 2500U/m2 im d1, Chidamide, 30mg, po, on d1，d5，d8，d12，d15，d19. The regimen was repeated every 3 weeks for 4 cycles followed by involved-field radiotherapy after got CR and PR (patients with efficacy of SD and PD withdrew from the study). Intensity-modulated radiation treatment was done by linear accelerator at 2.0 grays (Gy) per daily fraction with 5-6 weeks. The involved- field radiation (IFRT) dose was 54-56 Gy. During the radiotherapy, the anti-PD-1 antibody is administrated (200mg ivdrip, every 3 weeks) for 2 cycles. After the completion of radiotherapy, the subsequent 2 cycles of anti-PD-1 antibody + Peg-Asparaginase + Chidamide are administrated. After the end of all the above induction treatments , anti-PD-1 antibody (200mg ivdrip, every 3 weeks for up to 9 cycles) is given as maintenance therapy for 6 months (the total cycles of anti-PD-1 antibody is 17）. | Drug | Anti-PD-1 antibody+Peg-Asparaginase+Chidamide |
Primary outcome
Objective response rate (ORR)
Time frame: 12 weeks after the initiation of the treatment
complete remission rate + partial remission rate
Complete remission rate
Time frame: 12 weeks after the initiation of the treatment
complete remission rate
3 secondary outcomes
Progression Free Survival (PFS)
Time frame: Up to three years after the start of the study
Overall Survival (OS)
Time frame: Up to three years after the start of the study
Safety issue
Time frame: Up to one year after the end of the study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2020.
- Individual participant dataSharing planned: No
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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.
Hui Zhou, M.D. principal investigator
Department of Lymphoma and Hematology, Hunan Cancer Hospital
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 Anti-PD-1 antibody+Peg-Asparaginase+Chidamide in people with Immune Checkpoint Inhibitor and Chemotherapy Effect, run by Hunan Cancer Hospital at 1 site in China.
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 11 inclusion and 18 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 7 Jul 2020. 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 China. 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 Hui Zhou, M.D. (86-0731-89762281, zhouhui@hnca.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: 12 weeks after the initiation of the treatment). The study lists 2 primary outcomes in all. 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 7 Jul 2020.