Acute Myeloid Leukemia, in Relapsed or RefractoryPhase 2NCT04541277
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
A Phase 2 study testing Tislelizumab in people with Acute Myeloid Leukemia, in Relapsed or Refractory and Acute Myeloid Leukemia, Elderly, Unfit, run by Chinese PLA General Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, in Relapsed or Refractory, Acute Myeloid Leukemia, Elderly, Unfit, Acute Myeloid Leukemia With Positive Minimal Residual Disease
- What is being tested?
- Tislelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2020to 30 Aug 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
Dai-hong Liu, MD, 86-10-55499036 ext. 86-10-55499036, daihongrm@163.com
About this study
Official title: A Phase II, Single Arm Study of Tislelizumab Combined With DNA Demethylation Agent +/- CAG Regimen in the Treatment of Patients With High-risk AML or AML Patients Older Than 60 Years of Age Who Are Unfit for Intensive Chemotherapy
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
- Being tested
- Tislelizumab
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TislelizumabDrug
Also called Decitabine, Azacitidine, Cytarabine, Idarubicin
Tislelizumab combined with DNA demethylation agent +/- CAG regimen
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tislelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
The percentage of subjects with complete remission (CR) and incomplete hematological recovery (CRi) within 2 medication cycles.
Measured: 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.
Measured: Up to 3 months post-treatment
Duration of Remission (DOR)
The time from first obtaining CR or CRi to relapse or death from AML.
Measured: Up to 1 year post-treatment
Progression-free survival time (PFS)
the time from the day of treatment to relapse, progression or death (whichever occurs first is preferred).
Measured: Up to 1 year post-treatment
Overall survival (OS)
The time from the day of treatment to death.
Measured: Up to 1 year post-treatment
28-day response rate
The percentage of subjects with CR and CRi (calculated based on the best response) at the 28th day after treatment.
Measured: Up to 35 days post-treatment
Incidence of adverse events
The incidence of adverse events will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: Up to 35 days post-treatment
PD-L1 expression in acute myeloid leukemia bone marrow cells
The expression levels of PD-L1 in acute myeloid leukemia bone marrow cells will be assessed at the 28th day after each medication cycle.
Measured: Up to 1 year post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2020
- Study start1 Sep 2020 (estimated)
- Primary completion30 Aug 2021 (estimated)
- Study completion30 Aug 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia, in Relapsed or RefractoryStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daihong Liu, Chinese PLA General Hospital
- Investigators
- Dai-hong Liu, MD, Principal investigator, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04541277
- Sponsor's protocol ID
- PDCXG-RR&ELDER
- Status last verified
- Sep 2020
- First submitted
- 27 Aug 2020
- Last updated
- 9 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40313949Gao 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.
PubMed 37166484
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single Arm Study of Tislelizumab Combined With DNA Demethylation Agent +/- CAG Regimen in the Treatment of Patients With High-risk AML or AML Patients Older Than 60 Years of Age Who Are Unfit for Intensive Chemotherapy
- ClinicalTrials.gov ID
- NCT04541277
- Acronym / sponsor ID
- PDCXG-RR&ELDER
- Conditions
- Acute Myeloid Leukemia, in Relapsed or Refractory, Acute Myeloid Leukemia, Elderly, Unfit, Acute Myeloid Leukemia With Positive Minimal Residual Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- 1 Sep 2020 (estimated)
- Primary completion
- 30 Aug 2021 (estimated)
- Study completion
- 30 Aug 2022 (estimated)
- First posted
- 9 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tislelizumab with DAN hypmethylation agent +/- chemotherapy | Experimental | Drug: TislelizumabDecitabine, 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TislelizumabAlso: Decitabine, Azacitidine, Cytarabine, IdarubicinTislelizumab combined with DNA demethylation agent +/- CAG regimen | Drug | Tislelizumab with DAN hypmethylation agent +/- chemotherapy |
Primary outcome
Objective response rate (ORR)
Time frame: Up to 3 months post-treatment
The percentage of subjects with complete remission (CR) and incomplete hematological recovery (CRi) within 2 medication cycles.
7 secondary outcomes
The percentage of subjects with CR and CRi with negative minimal residual disease (MRD) within 2 cycles.
Time frame: Up to 3 months post-treatment
Duration of Remission (DOR)
Time frame: Up to 1 year post-treatment
Progression-free survival time (PFS)
Time frame: Up to 1 year post-treatment
Overall survival (OS)
Time frame: Up to 1 year post-treatment
28-day response rate
Time frame: Up to 35 days post-treatment
Incidence of adverse events
Time frame: Up to 35 days post-treatment
PD-L1 expression in acute myeloid leukemia bone marrow cells
Time frame: Up to 1 year post-treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
- Derived from this study: PubMed 40313949Zhou 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.
- Derived from this study: PubMed 37166484Gao 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dai-hong Liu, MD principal investigator
Chinese PLA General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tislelizumab in people with Acute Myeloid Leukemia, in Relapsed or Refractory and Acute Myeloid Leukemia, Elderly, Unfit, run by Chinese PLA General Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dai-hong Liu, MD (86-10-55499036 ext. 86-10-55499036, daihongrm@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: Up to 3 months post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04541277, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2020.