Sintilimab in Combination With Chidamide in Refractory and Relapsed AITL

April 2, 2021 updated by: Huiqiang Huang, Sun Yat-sen University

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)

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
83

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China
        • Sun Yat-Sen University Cancer Center
        • Principal Investigator:
          • Huiqiang Huang
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sintilimab+Chidamide
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.
Drug: Sintilimab
Sintilimab,200mg, ivd, d1
Other Names:
  • Tyvyt®
Drug: Chidamide
Chidamide,30mg,po,biw,d1-21
Other Names:
  • Epidaza

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR), complete response rate (CRR), partial response rate (PRR)
Time Frame: Up to 24 months
Assessed by the RECIL 2017 Response Criteria for Malignant Lymphoma
Up to 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Up to 24 months
PFS is defined as the time from the treatment date to the date of disease progression per the RECIL 2017 Response Criteria for Malignant Lymphoma or death regardless of cause.
Up to 24 months
Overall Survival (OS)
Time Frame: Up to 24 months
OS is defined as the time from treatment to the date of death.
Up to 24 months
Duration of Response (DOR)
Time Frame: Up to 24 months
Among participants who experience an objective response, DOR is defined as the date of their first objective response (which is subsequently confirmed) to disease progression per the RECIL 2017 Response Criteria for Malignant Lymphoma or death regardless of cause.
Up to 24 months
Time to disease response (TTR)
Time Frame: Up to 24 months
Among participants who experience an objective response, TTR is defined as the date of their first administration to the day of their first objective response (which is subsequently confirmed) per the RECIL 2017 Response Criteria for Malignant Lymphoma.
Up to 24 months
Time to progression (TTP)
Time Frame: Up to 24 months
Among all participants, TTP is defined as the date of their first administration to the day of disease progression per the RECIL 2017 Response Criteria for Malignant Lymphoma or death regardless of cause.
Up to 24 months
The frequency of adverse events (adverse events, AEs) and serious adverse events (SAEs)
Time Frame: Up to 24 months
An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAE were defined as AEs with onset during the treatment period or that are a consequence of a pre-existing condition that has worsened since baseline.
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 15, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 15, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 15, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 31, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 2, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 5, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 5, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 2, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SCRAT

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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