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Effect of DrugsPhase 2ORIENT-4NCT03228836

Efficacy and Safety Evaluation of IBI308 in Patients With Extranodal NK/T Cell Lymphoma Patients

A Phase 2 study testing Sintilimab in people with Effect of Drugs, run by Innovent Biologics (Suzhou) Co. Ltd. at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is phase II study. Efficacy and safety evaluation of IBI308 in patients with relapsed/refractory extranodal NK/T cell lymphoma, nasal type: a multicenter, single arm. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Effect of Drugs
What is being tested?
Sintilimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteChina
Study dates
23 Aug 2017to 28 Feb 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed ENKL-NT.
  • Relapsed or refractory ENKTL-NT. Being relapsed is defined as presence of new lesions at the primary location or other sites after achieving CR; being refractory is defined as any one of the followings: PD after 2 treatment cycles, PR not achieved after 4 treatment cycles, or CR not achieved after 6 treatment cycles. Patients who do not response or patients with relapsed disease or PD after autologous stem cell transplantation can enroll.
  • Must have been treated with asparaginase-based regimen (radiotherapy must be performed for stage I/II disease).
  • Long axis of a lesion > 15 mm or 18FDG-PET uptake by lesion.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) scores of 0-2.
  • Signed the inform consent form (ICF) and able to comply with the scheduled follow-up visits and related procedures required in the protocol.
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  • Between the ages of ≥18 to ≤70 years.
  • Life expectancy≥ 12 weeks.
  • Patients (female patients at childbearing age or male patients whose partners are at childbearing age) must take effective contraceptive measures during the entire course of the trial and within 90 days since the last dose of treatment.
  • Adequate organs and bone marrow functions, as defined below: Count of whole blood cells: absolute neutrophil count (ANC) ≥1.0×10^9/L, platelets (PLTs) count ≥ 50×10^9/L, hemoglobin (HGB) ≥ 8.0 g/L; granulocyte colony-stimulating factor, PLT, or red blood cell (RBC) transfusion has not been performed within 7 days prior to the test. Hepatic function: total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. Renal function:serum creatinine (Cr) ≤ 1.5 × ULN. Thyroid function: normal thyroid stimulating hormone (TSH) at baseline, or abnormal TSH at baseline with normal thiiodothronine (T3)/thiiodothronine (T4) and no symptoms.

Who cannot join

  • Patients with aggressive NK cell leukemia.
  • Patients with primary or secondary central nervous system (CNS) lymphoma.
  • Patients with severe hemophagocytic syndrome at initial diagnosis of ENKTL-NT.
  • Patients with pulmonary great vessel invasion.
  • Previous exposure to any anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies.
  • Enrolled in another interventional clinical study, unless only involved in an observational study (non-interventional) or in the follow-up phase of an interventional study.
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  • Received any investigational drug within 4 weeks prior to the first dose of study treatment.
  • The last dose of radiation or anti-tumor therapy (chemotherapy, targeted therapy or tumor embolization) was within 3 weeks prior to receiving the first dose of study treatment; the last dose of nitrosourea or mitomycin C treatment was within 6 weeks prior to receiving the first dose of study treatment.
  • Received immunosuppressants within 4 weeks prior to the first dose of study treatment, excluding local glucocorticoids administered by nasal, inhaled, or other topical routes, or systemic glucocorticoids of physiological doses (no more than 10 mg/day of prednisone or equivalents).
  • Received any live attenuated vaccine within 4 weeks prior to the first dose of study treatment, or is scheduled to receive live attenuated vaccine during the study period.
  • Received major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study treatment, or has unhealed wounds, ulcers, or fractures.
  • Active, known, or suspected autoimmune disease (see Appendix 6) or previous medical history of these diseases within 2 years (patients with vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic treatment, hypothyroidism only requiring thyroid replacement, or type I diabetes only requiring insulin can enroll).
  • Known history of primary immunodeficiency diseases.
  • Known active pulmonary tuberculosis.
  • Known history of allogeneic organ transplantation or allogeneic hem atopoietic stem cell transplantation.
  • Known to be allergic to any ingredients of monoclonal antibodies.
  • Uncontrolled concurrent diseases including but not limited to:
  • HIV-infected patients (positive anti-HIV antibody). Active or poorly controlled severe infections. Symptomatic congestive heart failure (NYHA Class III-IV) or symptomatic or poorly controlled arrhythmia.
  • Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) despite of standard treatment.
  • Any arterial thromboembolic events occurred within 6 months prior to enrollment, including myocardial infarction, unstable angina, cerebrovascular accident, or transient cerebral ischemic attack.
  • Life-threatening hemorrhagic events or grade 3-4 gastrointestinal/variceal hemorrhage requiring blood transfusion, endoscopy, or surgical treatment within 3 months prior to enrollment.
  • History of deep venous thrombosis, pulmonary embolism, or other serious thromboembolic events within 3 months prior to enrollment (implantable port or catheter-related thrombosis, or superficial venous thrombosis are not considered as serious thromboembolisms).
  • Uncontrolled metabolic disorders, non-malignant organ or systemic diseases, or cancer-related secondary diseases that may lead to higher medical risks and/or survival evaluation uncertainties.
  • Hepatic encephalopathy, hepatorenal syndrome, or cirrhosis with Child-Pugh grade B or C.
  • Bowel obstruction or history of the following diseases: inflammatory bowel disease or extensive bowel resection (partial colectomy or extensive small bowel resection accompanied with chronic diarrhea), Crohn's disease, and ulcerative colitis.
  • Acute or chronic diseases, psychiatric disorders, or laboratory abnormalities that may lead to the following consequences: increased investigational drug-related risks, or interference with interpreting trial results, and considered ineligible for participating in the trial by the investigators.
  • Known acute or chronic active hepatitis B (chronic HBV carriers or inactive HBsAg-positive patients can enroll if the HBV DNA < 1×10^3 copies/mL), or acute or chronic active hepatitis C (patients with negative HCV antibody can enroll; HCV RNA test is required for patients with positive HCV antibody, those test negative can enroll).
  • History of GI perforation and/or fistula without radical treatment within 6 months prior to the enrollment.
  • Known interstitial lung disease.
  • Clinically uncontrollable third spacing, such as pleural effusion and ascites that cannot be controlled by drainage or other methods prior to enrollment.
  • History of other primary malignant tumors, excluding:
  • History of radical treatment for malignant tumors with no evidence of tumor recurrence for more than 5 years prior to enrollment and with a very low risk of recurrence.
  • Adequately treated nonmelanoma skin cancer or lentigo maligna with no signs of disease recurrence.
  • Adequately treated carcinoma in situ with no signs of disease recurrence.
  • Pregnant or breastfeeding female patients.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Jiangsu Provincial Hospital

    Nanjing, Jiangsu

Other trials in China

About this study

Official title: Efficacy and Safety Evaluation of IBI308 in Patients With Relapsed/Refractory Extranodal NK/T Cell Lymphoma, Nasal Type: a Multicenter, Single Arm, Phase 2 Study (ORIENT-4)

This is phase II study. Efficacy and safety evaluation of IBI308 in patients with relapsed/refractory extranodal NK/T cell lymphoma, nasal type: a multicenter, single arm.

Read the detailed description

Extranodal NK/T cell lymphoma, nasal type(ENKTL) accounts for about 6% of all lymphomas in china. Epstein Barr virus (EBV) infection is found in all cases of ENKTL and maybe plays an important pathogenetic role.

Conventional anthrocycline-based regimens are not preferred to be used in ENKTL because of high p-glycoprotein expression. ORR of L-asparaginase based regimens is about 80% and no salvage regimens are recommended in ENKTL so far after failure of L-asparaginase based regimen.

Recently, a phase II clinical trial result demonstrated high ORR of anti-PD-1 antibody treatment in ENKTL.IBI308, a humanized monoclonal antibody (mAb) directly against PD-1, is investigated in this phase II Chinese ENKTL clinical trial.

Additionally the correlation between PD-L1 expression and the response to IBI308 treatment in Chinese ENKTL subjects will also be assessed.

Conditions
Effect of Drugs
Being tested
Sintilimab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03228836
Study groupRoleWhat they receive
Sintilimab (IBI308)ExperimentalNot described
Receives: Drug: Sintilimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) Before First PD

    The tumor assessment is according to Lugano 2014 Criteria and then International Working Group (IWG) 2007 Criteria after 24 weeks. Objective response is defined as best overall response (CR or PR) across all assessment time points during the period from enrollment to termination of trial treatment (per Lugano 2014 criteria during intial 24 weeks, per IWG 2007 criteria after 24 weeks). The primary efficacy endpoint is ORR evaluated using the 2014 Lugano Criteria before first progression disease (PD).

    Measured: Up to ~30 months (through database cut-off date of 28-February-2020)

Secondary outcomes (2)

  1. Progression Free Survival (PFS)

    PFS was defined as the time from the first dose to the first documented progressive disease (PD) per Lugano 2014 or death due to any cause, whichever occurred first. Participates who neither progress nor die were censored at the date of their last tumor imaging evaluation. Participates who did not have any tumor imaging evaluation after baseline were censored on the date of enrollment.

    Measured: Up to ~30 months (through database cut-off date of 28-February-2020)

  2. Duration of Response (DOR)

    DOR was defined as the time from first date of response to first PD per Lugano 2014 or death. Subjects who neither progress nor die were censored at the date of their last tumor imaging evaluation.

    Measured: Up to ~30 months (through database cut-off date of 28-February-2020)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jul 2017
  2. Study start23 Aug 2017
  3. Primary completion28 Feb 2020
  4. Study completion28 Feb 2020

Resources

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
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03228836
Sponsor's protocol ID
CIBI308D201
Acronym
ORIENT-4
Status last verified
Dec 2020
First submitted
22 Jul 2017
Last updated
12 Jan 2021
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Tao R, Fan L, Song Y, Hu Y, Zhang W, Wang Y, Xu W, Li J. Sintilimab for relapsed/refractory extranodal NK/T cell lymphoma: a multicenter, single-arm, phase 2 trial (ORIENT-4). Signal Transduct Target Ther. 2021 Oct 27;6(1):365. doi: 10.1038/s41392-021-00768-0.

    PubMed 34702811

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sintilimab in people with Effect of Drugs, run by Innovent Biologics (Suzhou) Co. Ltd. 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 10 inclusion and 35 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: finished, as of the sponsor's last update on 12 Jan 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 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?

Yes. Results are posted in the registry (first posted 17 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Response Rate (ORR) Before First PD (time frame: Up to ~30 months (through database cut-off date of 28-February-2020)). 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 NCT03228836, 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 12 Jan 2021.

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