PD-1 Inhibitor Combined With Azacytidine and Homoharringtonine，Cytarabine, G-CSF for Refractory or Relapsed AML

NCT04722952 | Unknown Phase 3

• 1 other identifier: SOOCHOW-HY-2020
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Immunotherapy; Refractory Leukemia; Relapsed Adult AML; Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; Refractory or Relapsed; Azacytidine; HAG regimen; PD-1 inhibitor

Outcome Measures

Primary Outcomes (1)

• Complete remission， Incomplete blood count recovery，Partial remission（CR+CRi+PR）

  Number of Participants (Responders) Achieving CR+CRi+PR After the Eighth Cycle Treatments

  8 months

Secondary Outcomes (4)

• Overall Response Rate （ORR）

  8 months

• Overall survival (OS)

  3 years

• Event free survival（EFS）

  3 years

• Progression free survival（PFS）

  3 years

Study Arms (1)

Anti-PD-1 mAb Combined With Azacytidine and HAG regimen

EXPERIMENTAL

Anti-PD-1 mAb combined with DNA methyltransferase inhibitor Azacytidine and HAG regimen

Drug: Visilizumab

Interventions

Visilizumab DRUG

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.

Also known as: Azacytidine, Homoharringtonine, Cytarabine

Anti-PD-1 mAb Combined With Azacytidine and HAG regimen

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Treatment without anthracycline or demethylation. Ability to comprehend the investigational nature of the study and provide informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

Related Publications (11)

• 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.

  PMID: 25852056 BACKGROUND

• 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.

  PMID: 21109304 BACKGROUND

• 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.

  PMID: 31200351 BACKGROUND

• 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.

  PMID: 12154409 BACKGROUND

• 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.

  PMID: 19911860 BACKGROUND

• 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.

  PMID: 26434886 BACKGROUND

• 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.

  PMID: 25823822 BACKGROUND

• 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.

  PMID: 30409776 BACKGROUND

• 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.

  PMID: 23619977 BACKGROUND

• 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.

  PMID: 25524177 BACKGROUND

• 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.

  PMID: 31153036 BACKGROUND

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Recurrence

Interventions

visilizumab; Azacitidine; Homoharringtonine; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Harringtonines; Alkaloids; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings; Arabinonucleosides

Study Officials

• Han Yue, Ph.D

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Han Yue, Ph.D

CONTACT

(0086)51267781856; hanyue@suda.edu.cn

Wu Depei, Ph.D

CONTACT

(0086)51267781856; drwudepei@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2020
• First Posted: January 25, 2021
• Study Start: May 1, 2021
• Primary Completion: January 1, 2023
• Study Completion: January 1, 2024
• Last Updated: December 3, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)