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

Primary Purpose

AML, MDS, Old Age; Debility

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Azacitidine

all trans retinoic acid

About this trial

This is an interventional treatment trial for AML focused on measuring acute myeloid leukemia, myelodysplastic syndromes, all-trans retinoic acid, azacitidine

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

The First Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Azacytidine Combined With ARTA

Azacytidine

Arm Description

Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle with ATRA 20mg tid by po on days 1-21 of every cycle 28 days

Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle

Outcomes

Primary Outcome Measures

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).

Overall survival (OS)

time from randomization to death from any cause, or last known date to be alive.

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.

Secondary Outcome Measures

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.

Incidence of systemic infections

Full Information

NCT ID

NCT05175508

First Posted

November 1, 2021

Last Updated

December 27, 2021

Sponsor

The First Affiliated Hospital of Soochow University

1. Study Identification

Unique Protocol Identification Number

NCT05175508

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Unknown status

Study Start Date

May 1, 2021 (Actual)

Primary Completion Date

May 1, 2022 (Anticipated)

Study Completion Date

May 1, 2023 (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

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

Brief 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

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

AML, MDS, Old Age; Debility, Hematologic Cancer

Keywords

acute myeloid leukemia, myelodysplastic syndromes, all-trans retinoic acid, azacitidine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Azacytidine Combined With ARTA

Arm Type

Experimental

Arm Description

Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle with ATRA 20mg tid by po on days 1-21 of every cycle 28 days

Arm Title

Azacytidine

Arm Type

Experimental

Arm Description

Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle

Intervention Type

Drug

Intervention Name(s)

Azacitidine

Other Intervention Name(s)

AZA

Intervention Description

Azacytidine 75mg/m2/d by IV on days 1-7 of every cycle 28 days

Intervention Type

Drug

Intervention Name(s)

all trans retinoic acid

Other Intervention Name(s)

ATRA

Intervention Description

ATRA 20mg tid by po on days 1-21 of every cycle 28 days

Primary Outcome Measure Information:

Title

Overall Response Rate （ORR)

Description

Time Frame

6 months

Title

Overall survival (OS)

Description

time from randomization to death from any cause, or last known date to be alive.

Time Frame

24months

Title

Progression-free survival (PFS)

Description

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.

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Percentage of Participants Achieving Transfusion Independence (TI) Who are Transfusion Dependent at Baseline

Description

Time Frame

6 months

Title

Incidence of systemic infections

Description

Incidence of systemic infections

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Han Yue, Ph.D

Phone

(0086)51267781856

hanyue@suda.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Wu Depei, Ph.D

Phone

(0086)51267781856

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

hanyuesz@163.com

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

30831622

Citation

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. No abstract available. Chinese.

Results Reference

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PubMed Identifier

28395438

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. No abstract available. Chinese.

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

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