Aza With or Without ATRA in Newly Diagnosed Unfit AML or Intermediate,High or Very High Risk MDS

AML Clinical Trial

Official title:

Azacitidine in Combination With or Without All-trans Retinoic Acid in Newly Diagnosed Unfit Acute Myeloid Leukemia or Intermediate,High or Very High Risk Myelodysplastic Syndromes (MDS) as Per IPSS-R Criteria

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05175508
• Other study ID #: SOOCHOW-HY-2021-03
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 1, 2021
• Est. completion date: May 1, 2023

Study information

• Verified date: April 2021
• Source: The First Affiliated Hospital of Soochow University
• Contact: Han Yue, Ph.D
• Phone: (0086)51267781856
• Email: hanyue[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, open-label, multicenter study to compare the efficacy and safety of AZA with or without ATRA in newly diagnosed unfit AML or Intermediate,High or Very High Risk MDS

Description:

Newly diagnosed unfit AML and Intermediate,High or Very High Risk Myelodysplastic Syndromes (MDS) as Per IPSS-R Criteria are unable to tolerate the intensive chemo-therapy regimens due to their old age and poor physical condition, resulting in limited overall survival. Nowadays, AZA are recommended for unfit acute myeloid leukemia or myelodysplastic syndromes patients with remission rate of 30%~34%. AZA with or without all-trans retinoic acid (ATRA) can cooperatively inhibit leukemia cell proliferation , induce apoptosis and differentiation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: May 1, 2023
• Est. primary completion date: May 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Chinese guidelines for the diagnosis and treatment of acute myeloid leukemia (2017 edition),excludes acute promyelocytic leukemia (M3?APL) and myelodysplastic syndromes(2017 edition)
• Be at least 18 years of age on day of signing informed consent
• Not suitable for newly diagnosed patients with intensive chemotherapy
• Not suitable for newly diagnosed patients with receiving hematopoietic stem cell transplantation
• The proportion of blast cells was below 50% in bone marrow
• Total white blood cell (WBC) count =10,000/µL;Must be able to swallow tablets

Exclusion Criteria:

• Malignant neoplasms with other progression
• Serious mental illness uncooperative
• Refusal to join the study

Related Conditions & MeSH terms

• AML
• Frailty
• Hematologic Cancer
• Hematologic Neoplasms
• MDS
• Old Age; Debility

Intervention

Drug:
• Azacitidine
Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle 28 days
• all trans retinoic acid
ATRA 20mg tid by po on days 1-21 of every cycle 28 days

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

References & Publications (11)

Chinese Society of Hematology, Chinese Medical Association. [Chinese guidelines for diagnosis and treatment of myelodysplastic syndromes (2019)]. Zhonghua Xue Ye Xue Za Zhi. 2019 Feb 14;40(2):89-97. doi: 10.3760/cma.j.issn.0253-2727.2019.02.001. Chinese. — View Citation

Delia M, Carluccio P, Buquicchio C, Vergine C, Greco G, Amurri B, Melpignano A, Melillo L, Cascavilla N, Guarini A, Capalbo S, Tarantini G, Mazza P, Pavone V, Di Renzo N, Specchia G. Azacitidine in the treatment of older patients affected by acute myeloid leukemia: A report by the Rete Ematologica Pugliese (REP). Leuk Res. 2015 Aug 20. pii: S0145-2126(15)30358-1. doi: 10.1016/j.leukres.2015.08.005. [Epub ahead of print] — View Citation

Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Récher C, Sandhu I, Bernal del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Döhner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. doi: 10.1182/blood-2015-01-621664. Epub 2015 May 18. — View Citation

Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. doi: 10.1016/S1470-2045(09)70003-8. Epub 2009 Feb 21. — View Citation

Leukemia & Lymphoma Group, Chinese Society of Hematology, Chinese Medical Association. [Chinese guidelines for diagnosis and treatment of adult acute myeloid leukemia (not APL) (2017)]. Zhonghua Xue Ye Xue Za Zhi. 2017 Mar 14;38(3):177-182. doi: 10.3760/cma.j.issn.0253-2727.2017.03.001. Chinese. — View Citation

Lübbert M, Grishina O, Schmoor C, Schlenk RF, Jost E, Crysandt M, Heuser M, Thol F, Salih HR, Schittenhelm MM, Germing U, Kuendgen A, Götze KS, Lindemann HW, Müller-Tidow C, Heil G, Scholl S, Bug G, Schwaenen C, Giagounidis A, Neubauer A, Krauter J, Brugger W, De Wit M, Wäsch R, Becker H, May AM, Duyster J, Döhner K, Ganser A, Hackanson B, Döhner H; DECIDER Study Team. Valproate and Retinoic Acid in Combination With Decitabine in Elderly Nonfit Patients With Acute Myeloid Leukemia: Results of a Multicenter, Randomized, 2 × 2, Phase II Trial. J Clin Oncol. 2020 Jan 20;38(3):257-270. doi: 10.1200/JCO.19.01053. Epub 2019 Dec 3. — View Citation

Pappa V, Anagnostopoulos A, Bouronikou E, Briasoulis E, Kotsianidis I, Pagoni M, Zikos P, Tsionos K, Viniou N, Meletis J, Papadaki H, Kioumi A, Galanopoulos A, Vervessou EC, Poulakidas E, Karmas P, Karvounis K, Symeonidis A. A retrospective study of azacitidine treatment in patients with intermediate-2 or high risk myelodysplastic syndromes in a real-world clinical setting in Greece. Int J Hematol. 2017 Feb;105(2):184-195. doi: 10.1007/s12185-016-2115-y. Epub 2016 Nov 4. — View Citation

Wu W, Lin Y, Xiang L, Dong W, Hua X, Ling Y, Li H, Yan F, Xie X, Gu W. Low-dose decitabine plus all-trans retinoic acid in patients with myeloid neoplasms ineligible for intensive chemotherapy. Ann Hematol. 2016 Jun;95(7):1051-7. doi: 10.1007/s00277-016-2681-3. Epub 2016 Apr 26. — View Citation

Xiang L, Dong W, Wang R, Wei J, Qiu G, Cen J, Chen Z, Zheng X, Hu S, Xie X, Cao X, Gu W. All-trans retinoic acid enhances the effect of 5-aza-2'-deoxycytidine on p16INK4a demethylation, and the two drugs synergistically activate retinoic acid receptor ß gene expression in the human erythroleukemia K562 cell line. Oncol Lett. 2014 Jul;8(1):117-122. Epub 2014 May 12. — View Citation

Xiang L, Wang R, Wei J, Qiu G, Cen J, Hu S, Xie X, Chen Z, Gu W. Retinoic acid receptor-ß gene reexpression and biological activity in SHI-1 cells after combined treatment with 5-aza-2'-deoxycytidine and all-trans retinoic acid. Acta Haematol. 2015;133(3):279-86. doi: 10.1159/000367586. Epub 2014 Nov 20. — View Citation

Xiang L, Zhou J, Gu W, Wang R, Wei J, Qiu G, Cen J, Xie X, Chen Z. Changes in expression of WT1 during induced differentiation of the acute myeloid leukemia cell lines by treatment with 5-aza-2'-deoxycytidine and all-trans retinoic acid. Oncol Lett. 2016 Feb;11(2):1521-1526. Epub 2015 Dec 23. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	Number of participants (responders) achieving ORR after the 6 cycle treatments,Overall response rate (ORR) based on the International Working Group (IWG)-2006 criteria, which include complete remission (CR), partial remission (PR), and major hematologic improvement (HI).	6 months
Primary	Overall survival (OS)	time from randomization to death from any cause, or last known date to be alive.	24months
Primary	Progression-free survival (PFS)	Progression-free survival (PFS) will be measured from time of enrolling in the clinical trial to the date on which disease progresses or the date on which the patient dies, whichever comes first.	24 months
Secondary	Percentage of Participants Achieving Transfusion Independence (TI) Who are Transfusion Dependent at Baseline	TI is when the participants who were transfusion dependent on RBC and/or Platelet at baseline achieve transfusion independence post baseline. TI is a period of at least 56 days with no transfusion after the date of the first dose of study drug to the last dose of study drug + 30 days, the initiation of post-treatment therapy, or death, whichever is earliest.	6 months
Secondary	Incidence of systemic infections	Incidence of systemic infections	6 months