Back to resultsPD-1 Inhibitor Combined With Azacytidine and Homoharringtonine，Cytarabine, G-CSF for Refractory or Relapsed AML
Primary Purpose
Immunotherapy, Refractory Leukemia, Relapsed Adult AML
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Visilizumab
Sponsored by
About this trial
This is an interventional treatment trial for Immunotherapy focused on measuring Acute Myeloid Leukemia, Refractory or Relapsed, Azacytidine, HAG regimen, PD-1 inhibitor
Eligibility Criteria
Inclusion Criteria:
Chinese guidelines for the diagnosis and treatment of relapsed and refractory acute myeloid leukemia (2017 edition)，excludes acute promyelocytic leukemia (M3、APL)
- Hematopoietic stem cell transplantation ≥3 months, Discontinue immunosuppressant ≥3 weeks, Patients without graft-versus-host disease；
- Be at least 18 years of age on day of signing informed consent.
- Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group（ECOG） Performance Scale
Demonstrate adequate organ function as defined below, all screening labs should be performed before treatment initiation：
- ALT(SGPT) less than or equal to 2.5 × Upper Limit of Norma（ULN）；
- AST (SGOT) less than or equal to 2.5 × ULN；
- Serum total bilirubin Less than or equal to 2.0 × ULN Note: If total bilirubin >2.0×ULN, subjects with Gilbert syndrome records are allowed to join the group
- Serum Creatinine ≥ 30 mL/min
- Total white blood cell (WBC) count ≤10,000/µL； Note: hydroxyurea therapy is allowed to reduce white blood cells to meet this inclusion criteria.white blood cells should be determined ≥24 hours after the last hydroxyurea administration. Final hydroxyurea administration should not ≤3 days prior to the first azacytidine administration.
- Treatment without anthracycline or demethylation. Ability to comprehend the investigational nature of the study and provide informed consent
Exclusion Criteria:
- Patients with chronic myeloid leukemia，AML of other myeloproliferative disorders Malignant neoplasms with other progression Those who can not control severe infections and other underlying diseases can not tolerate chemotherapy Patients with cardiac insufficiency： ejection fraction (EF)<30%，New York Heart Association（NYHA） standards，Cardiac insufficiency II or above Patients with liver and kidney dysfunction：Serum bilirubin (SB)≥2mg/dl，AST is 2.5 times higher than normal upper limit, serum creatinine (SCr) is more than 2.5 mg/dl Serious mental illness uncooperative Refusal to join the study
Sites / Locations
- The First Affiliated Hospital of Soochow UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Anti-PD-1 mAb Combined With Azacytidine and HAG regimen
Arm Description
Anti-PD-1 mAb combined with DNA methyltransferase inhibitor Azacytidine and HAG regimen
Outcomes
Primary Outcome Measures
Complete remission， Incomplete blood count recovery，Partial remission（CR+CRi+PR）
Number of Participants (Responders) Achieving CR+CRi+PR After the Eighth Cycle Treatments
Secondary Outcome Measures
Overall Response Rate （ORR）
Number of Participants (Responders) Achieving Overall Response Rate(ORR) After the Eighth Cycle Treatments
Overall survival (OS)
time from randomization to death from any cause
Event free survival（EFS）
The time between the beginning of the group and the occurrence of any event, including death, progression of the disease, chemotherapy regimen, conversion to chemotherapy, addition of other treatment, occurrence of fatal or intolerable side effects, etc
Progression free survival（PFS）
Time between the beginning of randomization and the progression (in any way) of tumorigenesis or (for any reason) death
Full Information
NCT ID
NCT04722952
First Posted
December 21, 2020
Last Updated
December 2, 2021
Sponsor
The First Affiliated Hospital of Soochow University
1. Study Identification
Unique Protocol Identification Number
NCT04722952
Brief Title
PD-1 Inhibitor Combined With Azacytidine and Homoharringtonine，Cytarabine, G-CSF for Refractory or Relapsed AML
Official Title
an Single Center，Single Arm, Phase 3 Study to Evaluate Efficacy and Safety of PD-1 Inhibitor Combined With Azacytidine and HAG Regimen for Patients With Relapsed or Refractory Acute Myeloid Leukemia.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2021 (Actual)
Primary Completion Date
January 1, 2023 (Anticipated)
Study Completion Date
January 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Soochow University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
This is an single center, single arm, phase 3 study to evaluate efficacy and safety of PD-1 Inhibitor combined with DNA methyltransferase inhibitor Azacytidine and HAG regimen for patients with relapsed and refractory acute myeloid leukemia.
Detailed Description
Treatment for Acute Myeloid Leukemia（AML） that has not responded to treatment (refractory) or has returned after treatment (relapsed) often do not work. Researchers want to see if an immunotherapy drug, combined with a less intense chemotherapy, may be able to help.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immunotherapy, Refractory Leukemia, Relapsed Adult AML, Acute Myeloid Leukemia
Keywords
Acute Myeloid Leukemia, Refractory or Relapsed, Azacytidine, HAG regimen, PD-1 inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Anti-PD-1 mAb Combined With Azacytidine and HAG regimen
Arm Type
Experimental
Arm Description
Anti-PD-1 mAb combined with DNA methyltransferase inhibitor Azacytidine and HAG regimen
Intervention Type
Drug
Intervention Name(s)
Visilizumab
Other Intervention Name(s)
Azacytidine, Homoharringtonine, Cytarabine
Intervention Description
Azacytidine 75mg/(m2.d) by IV on days 1-7 of every cycle. Anti-PD-1 mAb 200mg by IV on day 8 of every cycle. Homoharringtonine(HHT) 2mg/(m2.d) by IV on days 1-6 of every cycle Cytarabine 10mg/(m2.d) by SC on days 1-7 of every cycle Granulocyte colony-stimulating factor(G-CSF) 300ug/d by SC on days 1-7 of every cycle，until absolute neutrophil count(ANC) > 5X109／L or white blood cell（WBC）> 20X109／L.
Primary Outcome Measure Information:
Title
Complete remission， Incomplete blood count recovery，Partial remission（CR+CRi+PR）
Description
Number of Participants (Responders) Achieving CR+CRi+PR After the Eighth Cycle Treatments
Time Frame
8 months
Secondary Outcome Measure Information:
Title
Overall Response Rate （ORR）
Description
Number of Participants (Responders) Achieving Overall Response Rate(ORR) After the Eighth Cycle Treatments
Time Frame
8 months
Title
Overall survival (OS)
Description
time from randomization to death from any cause
Time Frame
3 years
Title
Event free survival（EFS）
Description
The time between the beginning of the group and the occurrence of any event, including death, progression of the disease, chemotherapy regimen, conversion to chemotherapy, addition of other treatment, occurrence of fatal or intolerable side effects, etc
Time Frame
3 years
Title
Progression free survival（PFS）
Description
Time between the beginning of randomization and the progression (in any way) of tumorigenesis or (for any reason) death
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Chinese guidelines for the diagnosis and treatment of relapsed and refractory acute myeloid leukemia (2017 edition)，excludes acute promyelocytic leukemia (M3、APL)
Hematopoietic stem cell transplantation ≥3 months, Discontinue immunosuppressant ≥3 weeks, Patients without graft-versus-host disease；
Be at least 18 years of age on day of signing informed consent.
Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group（ECOG） Performance Scale
Demonstrate adequate organ function as defined below, all screening labs should be performed before treatment initiation：
ALT(SGPT) less than or equal to 2.5 × Upper Limit of Norma（ULN）；
AST (SGOT) less than or equal to 2.5 × ULN；
Serum total bilirubin Less than or equal to 2.0 × ULN Note: If total bilirubin >2.0×ULN, subjects with Gilbert syndrome records are allowed to join the group
Serum Creatinine ≥ 30 mL/min
Total white blood cell (WBC) count ≤10,000/µL； Note: hydroxyurea therapy is allowed to reduce white blood cells to meet this inclusion criteria.white blood cells should be determined ≥24 hours after the last hydroxyurea administration. Final hydroxyurea administration should not ≤3 days prior to the first azacytidine administration.
Treatment without anthracycline or demethylation. Ability to comprehend the investigational nature of the study and provide informed consent
Exclusion Criteria:
Patients with chronic myeloid leukemia，AML of other myeloproliferative disorders Malignant neoplasms with other progression Those who can not control severe infections and other underlying diseases can not tolerate chemotherapy Patients with cardiac insufficiency： ejection fraction (EF)<30%，New York Heart Association（NYHA） standards，Cardiac insufficiency II or above Patients with liver and kidney dysfunction：Serum bilirubin (SB)≥2mg/dl，AST is 2.5 times higher than normal upper limit, serum creatinine (SCr) is more than 2.5 mg/dl Serious mental illness uncooperative Refusal to join the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Han Yue, Ph.D
Phone
(0086)51267781856
Email
hanyue@suda.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Wu Depei, Ph.D
Phone
(0086)51267781856
Email
drwudepei@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Han Yue, Ph.D
Organizational Affiliation
The First Affiliated Hospital of Soochow University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yue Han, professor
Phone
+86 13901551669
Email
hanyuesz@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
25852056
Citation
Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood. 2015 Jul 16;126(3):319-27. doi: 10.1182/blood-2014-10-551911. Epub 2015 Apr 7.
Results Reference
background
PubMed Identifier
21109304
Citation
Price SL, Lancet JE, George TJ, Wetzstein GA, List AF, Ho VQ, Fernandez HF, Pinilla-Ibarz J, Kharfan-Dabaja MA, Komrokji RS. Salvage chemotherapy regimens for acute myeloid leukemia: Is one better? Efficacy comparison between CLAG and MEC regimens. Leuk Res. 2011 Mar;35(3):301-4. doi: 10.1016/j.leukres.2010.09.002. Epub 2010 Nov 24.
Results Reference
background
PubMed Identifier
31200351
Citation
Tallman MS, Wang ES, Altman JK, Appelbaum FR, Bhatt VR, Bixby D, Coutre SE, De Lima M, Fathi AT, Fiorella M, Foran JM, Hall AC, Jacoby M, Lancet J, LeBlanc TW, Mannis G, Marcucci G, Martin MG, Mims A, O'Donnell MR, Olin R, Peker D, Perl A, Pollyea DA, Pratz K, Prebet T, Ravandi F, Shami PJ, Stone RM, Strickland SA, Wieduwilt M, Gregory KM; OCN; Hammond L, Ogba N. Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019 Jun 1;17(6):721-749. doi: 10.6004/jnccn.2019.0028.
Results Reference
background
PubMed Identifier
12154409
Citation
Christman JK. 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene. 2002 Aug 12;21(35):5483-95. doi: 10.1038/sj.onc.1205699.
Results Reference
background
PubMed Identifier
19911860
Citation
Keating GM. Azacitidine: a review of its use in higher-risk myelodysplastic syndromes/acute myeloid leukaemia. Drugs. 2009;69(17):2501-18. doi: 10.2165/11202840-000000000-00000.
Results Reference
background
PubMed Identifier
26434886
Citation
Gao S, Li Z, Fu JH, Hu XH, Xu Y, Jin ZM, Tang XW, Han Y, Chen SN, Sun AN, Wu DP, Qiu HY. Decitabine in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes, Which Combined with Complex Karyotype Respectively. Asian Pac J Cancer Prev. 2015;16(15):6627-32. doi: 10.7314/apjcp.2015.16.15.6627.
Results Reference
background
PubMed Identifier
25823822
Citation
Orskov AD, Treppendahl MB, Skovbo A, Holm MS, Friis LS, Hokland M, Gronbaek K. Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients: A rationale for combined targeting of PD-1 and DNA methylation. Oncotarget. 2015 Apr 20;6(11):9612-26. doi: 10.18632/oncotarget.3324.
Results Reference
background
PubMed Identifier
30409776
Citation
Daver N, Garcia-Manero G, Basu S, Boddu PC, Alfayez M, Cortes JE, Konopleva M, Ravandi-Kashani F, Jabbour E, Kadia T, Nogueras-Gonzalez GM, Ning J, Pemmaraju N, DiNardo CD, Andreeff M, Pierce SA, Gordon T, Kornblau SM, Flores W, Alhamal Z, Bueso-Ramos C, Jorgensen JL, Patel KP, Blando J, Allison JP, Sharma P, Kantarjian H. Efficacy, Safety, and Biomarkers of Response to Azacitidine and Nivolumab in Relapsed/Refractory Acute Myeloid Leukemia: A Nonrandomized, Open-Label, Phase II Study. Cancer Discov. 2019 Mar;9(3):370-383. doi: 10.1158/2159-8290.CD-18-0774. Epub 2018 Nov 8.
Results Reference
background
PubMed Identifier
23619977
Citation
Ivanoff S, Gruson B, Chantepie SP, Lemasle E, Merlusca L, Harrivel V, Charbonnier A, Votte P, Royer B, Marolleau JP. 5-Azacytidine treatment for relapsed or refractory acute myeloid leukemia after intensive chemotherapy. Am J Hematol. 2013 Jul;88(7):601-5. doi: 10.1002/ajh.23464. Epub 2013 May 30.
Results Reference
background
PubMed Identifier
25524177
Citation
Itzykson R, Thepot S, Berthon C, Delaunay J, Bouscary D, Cluzeau T, Turlure P, Prebet T, Dartigeas C, Marolleau JP, Recher C, Plantier I, Stamatoullas A, Devidas A, Taksin AL, Guieze R, Caillot D, Vey N, Ades L, Ifrah N, Dombret H, Fenaux P, Gardin C. Azacitidine for the treatment of relapsed and refractory AML in older patients. Leuk Res. 2015 Feb;39(2):124-30. doi: 10.1016/j.leukres.2014.11.009. Epub 2014 Nov 24.
Results Reference
background
PubMed Identifier
31153036
Citation
Santini V, Ossenkoppele GJ. Hypomethylating agents in the treatment of acute myeloid leukemia: A guide to optimal use. Crit Rev Oncol Hematol. 2019 Aug;140:1-7. doi: 10.1016/j.critrevonc.2019.05.013. Epub 2019 May 25.
Results Reference
background
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PD-1 Inhibitor Combined With Azacytidine and Homoharringtonine，Cytarabine, G-CSF for Refractory or Relapsed AML
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