Combined Inhibition of PD-1 and DNA Hypomethylating Agent +/- Chemotherapy in High-risk AML or Elderly Patients With AML Who Are Unfit for Intensive Chemotherapy

NCT04541277 | Unknown Phase 2

• 1 other identifier: PDCXG-RR&ELDER
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well tislelizumab combined with DNA hypomethylation agent +/- CAG regimen (cytarabine, idarubicin / Aclarithromycin, rhG-CSF/ PEG-rhG-CSF) work in treating patients with high-risk acute myeloid leukemia (AML) or AML patients older than 60 years of age who are unfit for standard-dose chemotherapy. The expressions of PD-1 and PD-L1 are increased in AML cells. However, blocking the immune checkpoint alone has limited efficacy as a single agent in highly proliferative leukemia cells. During the recovery period after cytotoxic chemotherapy, the activation of PD-1/PD-L1 pathway may be increased and DNA hypomethylation agents can also up-regulate PD-1, PD-L1 and PD-L2 in AML patients. The up-regulation and activation of above immune checkpoint molecules are related to chemotherapy resistance. Therefore, adding chemotherapy and epigenetic regulation agents to Immune checkpoint blockade therapy may work better through overcoming drug resistance in AML treatment.

Conditions

Acute Myeloid Leukemia, in Relapsed or Refractory; Acute Myeloid Leukemia, Elderly, Unfit; Acute Myeloid Leukemia With Positive Minimal Residual Disease

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  The percentage of subjects with complete remission (CR) and incomplete hematological recovery (CRi) within 2 medication cycles.

  Up to 3 months post-treatment

Secondary Outcomes (7)

• The percentage of subjects with CR and CRi with negative minimal residual disease (MRD) within 2 cycles.

  Up to 3 months post-treatment

• Duration of Remission (DOR)

  Up to 1 year post-treatment

• Progression-free survival time (PFS)

  Up to 1 year post-treatment

• Overall survival (OS)

  Up to 1 year post-treatment

• 28-day response rate

  Up to 35 days post-treatment

Study Arms (1)

Tislelizumab with DAN hypmethylation agent +/- chemotherapy

EXPERIMENTAL

Decitabine, 20 mg/m2/d, IV, on days 1-5; or Azacitidine, 75 mg/m2/d,SC, on days 1-7. Aclamycin hydrochloride, 20 mg/d, IV, on day 1, 3, and 5 (For relapse/resistance AML, on days 1-5.); or idarubicin hydrochloride,10 mg/d, IV, on day 1, 3, and 5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cytarabine,100 mg, IV, q12h/d. For patients with one of the following conditions, cytarabine,10 mg, SC, q12h/d: (1) There are obvious heart, lung, and kidney complications; (2) Bone marrow is hypoproliferative; (3) Age\> 75 years old; (4) Age\> 60 years old who are unfit for standard-dose chemotherapy. Recombinant human granulocyte colony stimulating factor injection, 5 μg/kg, SC, from day 0 to stop of chemotherapy after the WBC count exceeds 10.0×10\^9/L; or Pegylated recombinant human granulocyte stimulating factor injection Liquid, 100 μg/kg, SC, on day 0. Tislelizumab,200 mg, IV, on the next day after chemotherapy was stopped.

Drug: Tislelizumab

Interventions

Tislelizumab DRUG

Tislelizumab combined with DNA demethylation agent +/- CAG regimen

Also known as: Decitabine, Azacitidine, Cytarabine, Idarubicin, Aclarithromycin, Recombinant Human Granulocyte Colony Stimulating Factor, Pegylated Recombinant Human Granulocyte Colony Stimulating Factor

Tislelizumab with DAN hypmethylation agent +/- chemotherapy

Eligibility Criteria

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

You may qualify if:

• Patients or their legally authorized representative must provide written informed consent.
• Meet the diagnostic criteria for acute myeloid leukemia (AML) with positive minimal residual disease (MRD), excluding those patients who are MRD-positive or MRD recurrence after allogeneic hematopoietic stem cell transplantation (HSCT); or meet the diagnostic criteria for relapsed AML, excluding those experience relapsed within 2 months after HSCT from matched sibling donor or within 3 months after HSCT from alternative donor; or meet the diagnostic criteria for refractory AML, excluding those patients within 2 months after HSCT from matched sibling donor or those patients within 3 months after HSCT from alternative donor.
• Bone marrow (BM) or peripheral blood (PB) leukemia cells were measured to express PD-L1 within 3 months of entering the study.
• The toxic side effects of the last treatment should be restored.
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2.
• Creatinine =\< 1.5 x upper limit of normal (ULN). Serum bilirubin =\< 1.5 x ULN. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN.
• Karnofsky Performance Scale Index =\> 70.
• The expected survival period is at least 12 weeks.
• Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (b-hCG) pregnancy test result within 24 hours prior to the first dose of treatment and must agree to use an effective contraception method during the study and for 23 weeks after the last dose of the study drug; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 31 weeks following the last dose of study drug.

You may not qualify if:

• Patients with positive minimal residual disease (MRD) or MRD recurrence after HSCT; or patients who relapse or refractory within 2 months after HSCT from matched sibling donor or within 3 months after HSCT from alternative donor.
• History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years.
• Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 2 weeks prior to the first dose of the study drugs.
• Patients with any other known concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure New York Heart Association \[NYHA\] class III or IV, myocardial infarction within 6 months, and poorly controlled hypertension; chronic renal failure; or active uncontrolled infection) which, in the opinion of the investigator could compromise participation in the study.
• Patients unwilling or unable to comply with the protocol.
• Patients who are on steroids (\> 10 mg/day or equivalent) or immune suppression medications.
• Patients with autoimmune diseases (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's granulomatosis\]).
• Patients with a history of inflammatory bowel disease such as Crohn's disease and ulcerative colitis.
• Patients known to be positive for hepatitis B surface antigen expression or with active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months), or with known human immunodeficiency virus (HIV) infection.
• Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents.
• Females who are pregnant or lactating.
• Any grade of not controlled graft versus host disease.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

Related Publications (2)

• Zhou HS, Su YF, Wang J, Hu YL, Wang A, Xu L, Wang YZ, Zheng X, Li YQ, Min KL, Gao CJ, Liu DH, Gao XN. Updates from a single-center phase 2 study of PD-1 inhibitor combined with hypomethylating agent plus CAG regimen in patients with relapsed/refractory acute myeloid leukemia. Front Immunol. 2025 Apr 17;16:1533467. doi: 10.3389/fimmu.2025.1533467. eCollection 2025.

  PMID: 40313949 DERIVED

• Gao XN, Su YF, Li MY, Jing Y, Wang J, Xu L, Zhang LL, Wang A, Wang YZ, Zheng X, Li YF, Liu DH. Single-center phase 2 study of PD-1 inhibitor combined with DNA hypomethylation agent + CAG regimen in patients with relapsed/refractory acute myeloid leukemia. Cancer Immunol Immunother. 2023 Aug;72(8):2769-2782. doi: 10.1007/s00262-023-03454-y. Epub 2023 May 11.

  PMID: 37166484 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

tislelizumab; Decitabine; Azacitidine; Cytarabine; Idarubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic 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; Arabinonucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Dai-hong Liu, MD

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dai-hong Liu, MD

CONTACT

86-10-55499036; daihongrm@163.com

Xiao-ning Gao, MD

CONTACT

86-10-55499336; gaoxn@263.net

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: Director

Study Record Dates

• First Submitted: August 27, 2020
• First Posted: September 9, 2020
• Study Start: September 1, 2020
• Primary Completion: August 30, 2021
• Study Completion: August 30, 2022
• Last Updated: September 9, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)