Induction Chemotherapy Sequential Sintilimab Combined With Dual Epigenetic Drugs for ENKTL-HLH

NCT05008666 | Unknown Phase 2

• 1 other identifier: SELEN
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

ENKTL is a highly aggressive non-Hodgkin lymphoma closely related to EBV infection，and advanced patients often suffer from hemophagocytic lymphohistiocytosis (HLH). ENKTL-HLH lacks standard treatment and experiences a extremely poor prognosis. Anti-PD-1 antibody has shown good anti-tumor activity in ENKTL and play a potential role in EBV-HLH. Epigenetic drugs have been confirmed to exert synergistic anti-tumor activity with anti-PD-1 antibody. We next further explore the efficacy and safety of Sintilimab sequential combination of epigenetic drugs in ENKTL-HLH.

Conditions

Safety and Efficacy

Keywords

sintilimab; chidamide; azacitidine; Extranodal NK/T cell lymphoma; hemophagocytic lymphohistiocytosis

Outcome Measures

Primary Outcomes (3)

• Objective response rate (ORR) after end of treatment

  Assessed by the lymphoma response to immunomodulatory therapy criteria (LYRIC)

  [Time Frame: up to 24 months]

• Complete response rate (CRR) after end of treatment

  Assessed by the lymphoma response to immunomodulatory therapy criteria (LYRIC)

  [Time Frame: up to 24 months]

• Partial response rate (PRR) after end of treatment

  Assessed by the lymphoma response to immunomodulatory therapy criteria (LYRIC)

  [Time Frame: up to 24 months]

Secondary Outcomes (6)

• Progression-Free Survival (PFS)

  [Time Frame: Time Frame: up to 36 months]

• Overall Survival (OS)

  [Time Frame: up to 36 months]

• Duration of Response (DOR)

  [Time Frame: up to 36 months]

• Time to disease response (TTR)

  [Time Frame: up to 36 months]

• Time to progression (TTP)

  [Time Frame: Up to 36 months]

Study Arms (1)

L-DEP, Sintinimab+Chidamide, Sintinimab+Azacitidine

EXPERIMENTAL

【L-DEP】 L-asparaginase: 2000U/m2 d5, im Doxorubicin liposome: 25mg/m2 d1, ivd Etoposide: 100mg/m2 d1, d8, d15, ivd Methylprednisolone: 15mg/kg/day d1-3, 0.75mg/kg/day, d4-7, 0.25mg/kg/day, d8-14, ivd 【Sintinimab+Chidamide】 Sintinimab: 200mg，d1,ivd,q21d Chidamide：30mg biw, continued oral 【Sintinimab+Azacitidine】 Sintinimab:200mg，d1, ivd, q21d Azacitidine:75mg/m2, d1-d7, ih, q28d

Drug: Sintilimab; Drug: Chidamide; Drug: Azacitidine; Drug: L-DEP

Interventions

Sintilimab DRUG

1. To evaluate the short-term objective efficacy of sintilimab Sequential combined with chidamide and azacitidine in the treatment of ENKTL-HLH patients. 2. To evaluate the long-term efficacy and safety of sintilimab Sequential combined with chidamide and azacitidine in the treatment of ENKTL-HLH patients. 3. Exploring biomarkers that may have predictive effects.

L-DEP, Sintinimab+Chidamide, Sintinimab+Azacitidine

Chidamide DRUG

1. To evaluate the short-term objective efficacy of sintilimab Sequential combined with chidamide and azacitidine in the treatment of ENKTL-HLH patients. 2. To evaluate the long-term efficacy and safety of sintilimab Sequential combined with chidamide and azacitidine in the treatment of ENKTL-HLH patients. 3. Exploring biomarkers that may have predictive effects.

L-DEP, Sintinimab+Chidamide, Sintinimab+Azacitidine

Azacitidine DRUG

1. To evaluate the short-term objective efficacy of sintilimab Sequential combined with chidamide and azacitidine in the treatment of ENKTL-HLH patients. 2. To evaluate the long-term efficacy and safety of sintilimab Sequential combined with chidamide and azacitidine in the treatment of ENKTL-HLH patients. 3. Exploring biomarkers that may have predictive effects.

L-DEP, Sintinimab+Chidamide, Sintinimab+Azacitidine

L-DEP DRUG

L-DEP

L-DEP, Sintinimab+Chidamide, Sintinimab+Azacitidine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• The age at the time of signing the ICF is ≥18 years old and ≤75 years old.
• ENKTL confirmed by the research center histopathology and HLH conformed by the HLH-2004 diagnostic criteria.
• Available tumor tissue samples (10-15 unstained, fresh-frozen, paraffin-embedded \[FFPE\] glass slides) obtained from past or fresh coarse needle puncture or excision.
• Newly treated or refractory or relapsed ENKTL that has failed treatment with asparaginase-based chemotherapy or radiochemotherapy.
• HLH occurred for the first time.
• Eastern cooperative oncology group score:0-2.
• Estimated survival≥3 months.
• There must be at least 1 evaluable or measurable lesion that meets the RECIL 2017 lymphoma standard \[evaluable lesion: 18FDG/PET examination Shows increased local uptake in lymph nodes or extranodal areas (higher than liver) and PET and/or Computed Tomography (CT) features are consistent with lymphoma manifestations; measurable lesions: nodular lesions longer than 15mm or extranodal lesions longer diameter \>10mm (if the only measurable lesion has received radiotherapy in the past, there must be evidence of imaging progression after radiotherapy) and accompanied by increased 18FDG uptake\]. No measurable lesion and the diffuse increased 18FDG uptake in the liver would be excluded.
• Sufficient organ function, no serious heart, lung, kidney, thyroid dysfunction and immune deficiency:
• Hemoglobin ≥6 g/dL (no growth factor support or blood transfusion was used within 7 days before platelet measurement);
• Platelets ≥60×109/L (no growth factor support or blood transfusion was used within 7 days before platelet measurement);
• Serum creatinine ≤1.5 times the upper limit of normal (Upper Limit Normal, ULN), or creatinine clearance ≥40mL/min (estimated according to the Cockcroft-Gault formula);
• Serum total bilirubin ≤ 5 times ULN (unless it is confirmed to have Gilbert syndrome);
• Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) ≤10 times ULN;

You may not qualify if:

• Invasive natural killer cell leukemia.
• Primary central nervous system lymphoma or secondary central nervous system involvement.
• Have received other anti-tumor therapy (including chemotherapy, immunotherapy, targeted therapy, and allowed to receive L-DEP or HLH-94/04 regimen for HLH).
• Have received allogeneic organ transplantation.
• Received allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 3 years before study drug administration (Patients who have received allo-HSCT more than 3 years before study drug administration and currently have no graft-versus-host reaction can be included in the group).
• Participating in other clinical studies, or planning to start the treatment of this study is less than 4 weeks from the end of the previous clinical study.
• An autologous hematopoietic stem cell transplantation(ASCT) was performed within 90 days.
• Received immune checkpoint inhibitors (anti-PD-1/PD-L1/CTLA-4 antibodies and other drugs) within half a year.
• Have received histone deacetylase inhibitor or DNA methyltransferase inhibitor treatment within 1 year before the study drug administration.
• Suffer from active autoimmune diseases that require systemic treatment in the past two years (glucocorticoid replacement therapy is not considered systemic treatment, such as type I diabetes, hypothyroidism that requires only thyroxine replacement therapy, only Patients with low adrenal function or hypopituitarism who need to receive physiological doses of glucocorticoid replacement therapy); patients with autoimmune diseases who do not require systemic treatment in the past two years can be included in the group.
• Subjects who need to receive systemic glucocorticoid therapy or other immunosuppressive therapy due to certain conditions within 14 days before starting the research treatment \[Subjects are allowed to use topical, ocular, intra-articular, intranasal and inhaled types glucocorticoid therapy (very low systemic absorption); high-dose intravenous or oral glucocorticoid therapy for HLH is allowed; short-term (≤ 7 days) use of glucocorticoid for preventive treatment (such as contrast agent allergy) or for the treatment of non-autoimmune diseases (for example, delayed-type hypersensitivity reactions caused by contact allergens)\].
• Suffered from other malignant tumors in the past 5 years, except for skin basal cell carcinoma, skin squamous cell carcinoma, breast carcinoma in situ and cervical carcinoma in situ that have undergone radical treatment.
• Received systemic anti-tumor therapy within 28 days before starting the study drug treatment, including chemotherapy, immunotherapy, biological therapy (tumor vaccine, cytokines, or growth factors), etc. \[L-DEP or HLH-94/04 based regimens are allowed for HLH; G-CSF,IL-11, TPO, EPO therapy are allowed.
• Received major surgery within 28 days or radiation therapy within 90 days.
• Received traditional Chinese medicine or Chinese patent medicine treatment within 7 days.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Department of Medical Oncology,Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell; Lymphohistiocytosis, Hemophagocytic

Interventions

sintilimab; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; Azacitidine

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Huiqiang Huang, Professor

CONTACT

+86 020 87343350; huanghq@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 14, 2021
• First Posted: August 17, 2021
• Study Start: December 1, 2021
• Primary Completion: November 30, 2022
• Study Completion: April 30, 2023
• Last Updated: August 17, 2021

Record last verified: 2021-08

Locations

CN (1)