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Efficacy and Safety Evaluation of IBI308 in Patients With Extranodal NK/T Cell Lymphoma Patients (ORIENT-4)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03228836
Recruitment Status : Active, not recruiting
First Posted : July 25, 2017
Last Update Posted : September 4, 2019
Information provided by (Responsible Party):
Innovent Biologics (Suzhou) Co. Ltd.

Brief 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.

Condition or disease Intervention/treatment Phase
Effect of Drugs Drug: PD-1 Antibody Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : August 31, 2017
Actual Primary Completion Date : February 7, 2018
Estimated Study Completion Date : February 2, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: IBI308 Drug: PD-1 Antibody
IBI308 200mg/3 weeks

Primary Outcome Measures :
  1. ORR [ Time Frame: up to 24 months after randomization] ]

    ORR(objective response rate):[time frame: up to 24 months after randomization] 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).

    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)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histopathologically confirmed extranodal NK/T cell lymphoma, nasal type (ENKTL).
  2. Relapsed refractory ENKTL Relapsed disease is defined as occurrence of new lesions after CR; Refractory disease should meet any of below criteria: PD after 2 cycles, have not met PR after 4 cycles etc, have not met CR after 6 cycles.
  3. After failure of L-Asparaginase/Pegaspargase based regimen (stage I/II diseases should have received local radiotherapy)
  4. Subjects didn't response to or progressed after ASCT are eligible.
  5. At least one lesion with long axis>15 mm or uptake on 18FDG-PET/CT
  6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2.
  7. Signed written informed consent form and willing and able to comply with scheduled visits and other requirements of the study.
  8. 18≤ Age ≤70 years.
  9. Life expectancy of at least 12 weeks.
  10. Subjects of reproductive potential must be willing to use adequate contraception during the course of the study and through 90 days after the last dose of study treatment.
  11. Adequate organ and bone marrow function:

    1. Count of Blood Cells: absolute neutrophil count (ANC) ≥ 1 × 109 / L; platelet count (PLT) ≥ 50 × 109 / L; hemoglobin content (HGB) ≥ 8.0 g / Dl; no granulocyte colony-stimulating factor, platelet or red blood cells infusion in the last 14 days.
    2. Liver function: serum total bilirubin (TBIL) ≤ 1.5 × normal upper limit (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.
    3. Renal function: serum creatinine (Cr) ≤ 1.5 × ULN
    4. Thyroid function: Subjects with asymptomatic thyroid stimulating hormone (TSH) increase can be eligible.

Exclusion Criteria:

  1. Aggressive NK-cell leukemia.
  2. Known central nervous system lymphoma.
  3. Initial diagnosis with serious hemophagocytic syndrome.
  4. Infiltration to major pulmonary vessels.
  5. Prior therapy with anti-PD-1,anti-PD-L1,anti-CTLA4 antibody.
  6. Currently participating in an interventional clinical study, unless participating in observational study or during follow-up period of an interventional study.
  7. Received any investigational agent within 4 weeks of the first dose of study treatment.
  8. Received radiotherapy or anti-tumor therapy (chemotherapy, targeted therapy, tumor immunotherapy or arterial embolization) within 3 weeks of the first dose of study treatment; received nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment.
  9. Received systemic treatment with corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive treatments within 4 weeks of first dose. Inhaled or topical steroids and adrenal replacement steroid are permitted.
  10. Received attenuated live vaccine within 4 weeks of the first dose of study treatment or plan to receive attenuated live vaccine during study period.
  11. Underwent major surgery (craniotomy, thoracotomy or laparotomy) within 4 weeks of the first dose of study treatment or open wound, ulcer or fracture.
  12. Unrecovered toxicity (grade >1, according to NCI CTCAE 4.03) due to prior anti-tumor therapy before the first dose of study treatment.
  13. Active, known or suspected autoimmune disease history within 2 years (subjects with vitiligo, psoriasis, alopecia or Grave's disease without systemic treatment, or autoimmune thyroiditis and type I diabetes mellitus only requiring hormone replacement in recent 2 years are permitted to enroll).
  14. Known primary immunodeficiency history.
  15. Active tuberculosis.
  16. Known history of allogeneic organ or allogeneic hemopoietic stem cell transplantation.
  17. Known allergy or hypersensitivity to any monoclonal antibodies or any components used in preparation.
  18. Uncontrolled concomitant disease, including but not limited to :

    1. Human Immunodeficiency Virus (HIV) infection (HIV antibody positive)
    2. Active or uncontrolled severe infection
    3. Symptomatic congestive heart failure (New York Heart Association grade II-IV) or symptomatic, uncontrolled arrhythmia
    4. Uncontrolled hypertension (SBP ≥ 160mmHg or DBP ≥ 100mmHg)
    5. Prior arterial thromboembolism event, including myocardial infarction, unstable angina, stroke and transient ischemic attack within 6 months of enrollment
    6. Prior life-threatening blood loss or grade 3/4 gastrointestinal/varicosity bleeding requiring blood infusion, endoscopic or surgical intervention within 3 months of enrollment
    7. Prior deep vein thrombosis, pulmonary embolism or any other severe thromboembolism events (implanted port or catheter caused thrombosis, or superficial vein thrombosis are not considered as severe thromboembolism) within 3 months before enrollment
    8. History of uncontrolled metabolic disorder, non-malignant organ or systemic disease or secondary carcinomatous reaction, with high medical risk and/or uncertainty of life expectancy evaluation
    9. With hepatic encephalopathy, hepatorenal syndrome or hepatic cirrhosis of Child-Pugh grade B or higher.
    10. History of intestinal obstruction or the following diseases: inflammatory bowel disease or extensive bowel resection (partial colonic resection or extensive small bowel resection, concomitant with chronic diarrhea), Crohn's disease, ulcerative colitis or chronic diarrhea
    11. Other acute or chronic diseases, mental illness, or abnormal laboratory test results that may lead to the following outcomes: increase the risk of participating in study or study drug administration, or interfere with the interpretation of the study results and considered by investigator as "NOT" eligible to participate in this study
  19. Known acute or chronic active hepatitis B infection (chronic HBV carrier or non-active HBsAg positive subject is eligible) or acute or chronic active hepatitis C (HCV antibody negative subjects are eligible; HCV antibody positive subjects need further HCV RNA examination and can be enrolled if the results are negative)
  20. History of gastrointestinal perforation and /or fistula within 6 months of enrollment
  21. Subjects with a history of interstitial lung disease
  22. Uncontrolled third space effusion, eg. ascites or pleural effusion.
  23. Other primary malignancy, with the exception of:

    1. Curative malignancy, without active disease within 5 years and with very low recurrence risk
    2. Non-melanoma skin cancer or malignant freckle-like nevus with adequate treatment and no evidence of recurrence ;
    3. Adequately treated in-situ carcinoma
  24. Women who are pregnant or nursing.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03228836

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China, Jiangsu
Jiangsu Provincial Hospital
Nanjing, Jiangsu, China
Sponsors and Collaborators
Innovent Biologics (Suzhou) Co. Ltd.
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Principal Investigator: Yong Ji Li, Master The First Affiliated Hospital with Nanjing Medical University

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Responsible Party: Innovent Biologics (Suzhou) Co. Ltd. Identifier: NCT03228836     History of Changes
Other Study ID Numbers: CIBI308D201
First Posted: July 25, 2017    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma, T-Cell
Lymphoma, Extranodal NK-T-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Immunologic Factors
Physiological Effects of Drugs