Clinical Trials /

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

NCT03228836

Description:

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.

Related Conditions:
  • Nasal Type Extranodal NK/T-Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

    <li>Brief Title: Efficacy and Safety Evaluation of IBI308 in Patients With Extranodal NK/T Cell Lymphoma Patientsli><li>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)li>

Clinical Trial IDs

    <li>ORG STUDY ID: CIBI308D201li><li>NCT ID: NCT03228836li>

Conditions

    <li>Effect of Drugsli>

Interventions

<td>PD-1 Antibodytd><td/><td>IBI308td>
DrugSynonymsArms

Purpose

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.

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.
    

Trial Arms

<td>IBI308td><td>Experimentaltd><td/><td>
    <li>PD-1 Antibodyli>
td>
NameTypeDescriptionInterventions

Eligibility Criteria

        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.
      
<td>Maximum Eligible Age:td><td>70 Yearstd><td>Minimum Eligible Age:td><td>18 Yearstd><td>Eligible Gender:td><td>Alltd><td>Healthy Volunteers:td><td>Notd>

Primary Outcome Measures

<td>Measure:td><td>ORRtd><td>Time Frame:td><td>up to 24 months after randomization]td><td>Safety Issue:td><td/><td>Description:td><td>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)td>

Details

<td>Phase:td><td>Phase 2td><td>Primary Purpose:td><td>Interventionaltd><td>Overall Status:td><td>Not yet recruitingtd><td>Lead Sponsor:td><td>Innovent Biologics (Suzhou) Co. Ltd.td>

Last Updated

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