Sintilimab in Combination With Chidamide in Refractory and Relapsed AITL

Brief Title

Sintilimab in Combination With Chidamide in Refractory and Relapsed AITL

Official Title

Safety and Efficacy of Sintilimab(S) in Combination With Histone Deacetylase Inhibitor (Chidamide, C) in Refractory and Relapsed (R) Angioimmunoblastic T-cell Lymphoma (AT): A Single-arm, Multicenter Phase II Study(SCRAT)

Brief Summary

      Angioimmunoblastic T-cell lymphoma (AITL) belongs to a subtype of peripheral T-cell lymphoma
      (PTCL) and is also a distinct type of non-Hodgkin lymphoma (NHL). The clinical outcomes of
      AITL is poor and optimal treatment strategies for AITL have not been fully defined. Patients
      with disseminated or relapsed disease have a very poor outcome, and there is no standard
      management for relapsed or refractory disease. Epigenetic drugs have been widely used to
      treat patients with refractory/relapse AITL. Several phase II clinical trails demonstrated
      the ORR of 33-50% in patients with r/r AITL treated with HDAC inhibitors (including
      Belimastat, Romidepsin, Chidamide). HDAC inhibitors are important drugs for the current
      treatment of AITL, but still more than half of the patients can not benefit from it.
      PD1/PD-L1 blockade was a potent strategy for r/r PTCL in two small sample studies. Current
      studies have found that HDACi can upregulate the expression of PDL1, In vivo testing of
      C57BL/6 mice revealed a synergistic tumor suppression after combining HDACi and PD-1
      blockade. We carried out a single, open-label, multicenter clinical trial enrolled patients
      with relapsed/refractory AITL to investigate the safety and efficacy of sintilimab in
      combination with chidamide.
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Objective response rate (ORR), complete response rate (CRR), partial response rate (PRR)

Secondary Outcome

 Progression-Free Survival (PFS)

Condition

Angioimmunoblastic T-cell Lymphoma

Intervention

Sintilimab

Study Arms / Comparison Groups

 Sintilimab+Chidamide
Description:  Participants will receive Sintilimab,200mg, ivd, d1; Chidamide,30mg,po,biw,d1-21; repeated every 3 weeks(up to 1 year) until disease progression, intolerable toxicity, death, or termination of the study for any reason.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

83

Start Date

April 15, 2021

Completion Date

April 15, 2023

Primary Completion Date

April 15, 2022

Eligibility Criteria

        Inclusion Criteria:

          1. Volunteer to participate in clinical research; fully understand and know the research
             and sign the Informed Consent Form (ICF); willing to follow and have the ability to
             complete all trial procedures;

          2. Aged 18-75 years old male or female;

          3. Angioimmunoblastic T-cell lymphoma confirmed by histopathology examination;

          4. Paraffin tissue specimens or fresh puncture tissue specimens are available;

          5. Patients with refractory or relapsed angioimmunoblastic T-cell lymphoma after
             anthracycline-contained regimen treatment. Refractory is defined as: patients did not
             get partial remission (PR) or better responses after first line treatment or disease
             progression within 6 months of the last protocol;

          6. Eastern cooperative oncology group score: 0-1;

          7. Estimated survival ≥ 3 months;

          8. There must be at least one evaluate able or measurable lesion that meets the RECIL
             2017 Lymphoma criteria [evaluable lesion: 18Ffluorodeoxyglucose/ Positron Emission
             Tomography (18FDG/PET) examination showing increased lymph node or extranodal uptake
             (higher than liver) and PET and/or computed tomography (Computed Tomography) CT)
             features are consistent with lymphoma findings; lesions can be measured: nodular
             lesions > 15mm or extranodal lesions > 10mm (if the only measurable lesion has
             received radiotherapy in the past, there must be evidence of radiological progress
             after radiotherapy), and accompanied by increased 18FDG uptake). Except for this,
             there is no measurable increase in diffuse 18FDG uptake in the liver;

          9. Adequate organ and bone marrow function, no severe hematopoietic dysfunction, cardiac,
             pulmonary, liver, kidney, thyroid dysfunction and immune deficiency (no blood
             transfusion, granulocyte colony stimulating factor or other medical support was
             received within 14 days prior to the use of the research drug): 1) The absolute value
             of neutrophils (>1.0×10^9/L); 2) platelet count (> 75×10^9/L); 3) Hemoglobin (> 9 g/
             dL); 4) Upper Limit Normal (ULN) or creatinine clearance rate (>40 mL/ min) of serum
             creatinine (<1.5 times normal value upper limit) (estimated by Cockcroft-Gault
             formula); 5) Serum total bilirubin < 1.5 times ULN; 6) Aspartate Aminotransferase
             (AST), Alanine Aminotransferase (ALT) = 2.5 times ULN; 7) Coagulation function:
             International Normalized Ratio (INR) = 1.5 times ULN; Prothrombin Time (PT), Activated
             Partial Thromboplastin Time (APTT) = 1.5 times ULN (unless the subject is receiving
             anticoagulant therapy and PT and APTT are using anticoagulant therapy at screening
             time). Within the expected range; 8) Thyrotropin (TSH) or free thyroxine (FT4) or free
             triiodothyronine (FT3) were all within the normal range (+10%);

         10. There was no evidence that subjects had difficulty breathing at rest, and the measured
             value of pulse oximetry at rest was more than 92%;

         11. Participants must pass a pulmonary function test (PFT) to confirm that forced
             expiratory volume (FEV1)/forced vital capacity (FVC) in the first second is more than
             60%, unless it is a large mediastinal mass caused by lymphoma that cannot meet this
             standard; carbon monoxide diffusion (DLCO), FEV1 and FVC are all above 50% of the
             predicted value; all PFT results must be obtained within four weeks before the first
             administration;

         12. Subjects who have received antineoplastic therapy should be admitted to the group only
             after the toxicity of the previous treatment has returned to the level of Common
             Terminology Criteria for Adverse Events (CTCAE) V5.0 grade score < 1 or baseline
             level; the level 2 toxicity caused by previous antineoplastic treatment is
             irreversible and is not expected to deteriorate during the study period. (e.g.
             thrombocytopenia, anemia, neurotoxicity, alopecia and hearing loss) can be enrolled
             with the consent of the researchers;

         13. Women of Childbearing Potential (WOBCP) must undergo a serum pregnancy test within
             seven days before the first medication and the results are negative. WOBCP or men and
             their WOBCP partners should agree to take effective contraceptive measures from the
             signing of ICF until six months after the last dose of the research drug is used.

        Exclusion Criteria:

          1. Hemophagocytic syndrome;

          2. Primary central nervous system lymphoma or secondary central nervous system
             involvement;

          3. Received organ transplantation in the past;

          4. Patients who received allogeneic hematopoietic stem cell transplantation within three
             years before the drug was given (patients who received allogeneic hematopoietic stem
             cell transplantation more than three years before the drug was given and who currently
             have no graft-versus-host response can be enrolled);

          5. Participating in other clinical studies or planning to start this study is less than 4
             weeks from the end of the previous clinical study;

          6. Autologous hematopoietic stem cell transplantation was performed within 90 days before
             the start of the study;

          7. Treated with immune checkpoint inhibitors or histone deacetylase inhibitors within one
             year before administration;

          8. Patients with active autoimmune diseases requiring systematic treatment in the past
             two years (hormone replacement therapy is not considered systematic treatment, such as
             type I diabetes mellitus, hypothyroidism requiring only thyroxine replacement therapy,
             adrenocortical dysfunction or pituitary dysfunction requiring only physiological doses
             of glucocorticoid replacement therapy); Patients with autoimmune diseases who do not
             require systematic treatment within two years can be enrolled;

          9. Begin the study on subjects requiring systemic glucocorticoid therapy or other
             immunosuppressive therapy for a given condition within 14 days before treatment
             [allowing subjects to use local, ocular, intra-articular, intranasal and inhaled
             glucocorticoid therapy (with very low systemic absorption); and allowing short-term (<
             7 days) glucocorticoid prophylaxis (e.g., contrast agent overdose) Sensitivity) or for
             the treatment of non-autoimmune diseases (e.g. delayed hypersensitivity caused by
             contact allergens);

         10. In the past five years, patients with other malignant tumors have undergone radical
             treatment, except for basal cell carcinoma of skin, squamous cell carcinoma of skin,
             carcinoma in situ of breast and carcinoma in situ of cervix.

         11. Begin the study and receive systemic antineoplastic therapy within 28 days before
             treatment, including chemotherapy, immunotherapy, biotherapy (cancer vaccine,
             cytokines, or growth factors that control cancer), etc.;

         12. The study began with major surgery within 28 days before treatment or radiotherapy
             within 90 days before treatment;

         13. Start the study and receive Chinese herbal medicine or Chinese patent medicine
             treatment within 7 days before treatment;

         14. Begin research on live vaccination (except influenza attenuated vaccine) within 28
             days before treatment;

         15. History of human immunodeficiency virus (HIV) infection and/or patients with acquired
             immunodeficiency syndrome are known;

         16. Patients with active hepatitis B or active hepatitis C. Patients who are positive for
             hepatitis B Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening
             stage must pass further detection of hepatitis B Virus (HBV) DNA titer (no more than
             2500 copies/mL or 500 IU/mL) and HCV RNA (no more than the lower limit of the
             detection method) in the row. In addition to active hepatitis B or hepatitis C
             infections requiring treatment, group trials can be conducted. Hepatitis B carriers,
             stable hepatitis B (DNA titer should not be higher than 2500 copies/mL or 500 IU/mL)
             after drug treatment, and cured hepatitis C patients can be enrolled in the group;

         17. Patients with active pulmonary tuberculosis;

         18. Start studying any active infections requiring systemic anti-infective treatment
             within 14 days of treatment.

         19. Pregnant or lactating women;

         20. People with known history of alcoholism or drug abuse;

         21. Have uncontrollable complications, including but not limited to symptomatic congestive
             heart failure, uncontrollable hypertension, unstable angina, active peptic ulcer or
             hemorrhagic diseases;

         22. History of interstitial lung disease or non-infectious pneumonia. Subjects who had
             previously had non-infectious pneumonia caused by drugs or radiation but had no
             symptoms were allowed to enter the group;

         23. The QTcF interval is more than 450 msec, unless it is secondary to bundle branch
             block;

         24. Past psychiatric history; incapacitated or restricted;

         25. According to the researchers' judgment, patients' underlying condition may increase
             their risk of receiving research drug treatment, or confuse their judgment on toxic
             reactions;

         26. Other researchers consider it unsuitable for patients to participate in this study
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT04831710

Organization ID

SCRAT


Responsible Party

Principal Investigator

Study Sponsor

Sun Yat-sen University


Study Sponsor

, , 


Verification Date

April 2021