DLAAG in the Treatment of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome With Blast Excess

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate of the clinical efficacy and safety of DLAAG protocol in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome with blast excess

Official Title
-----------------
Clinical Efficacy and Safety of DLAAG Protocol in the Treatment of Refractory/Relapse of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome With Blast Excess: a Multicenter, Single-arm, Prospective Clinical Study

Conditions
-----------------
Acute Myeloid Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
-----------------
* Drug: Decitabine
* Drug: Cytarabine
* Drug: All-transretinoic acid
* Drug: G-CSF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: corresponding to the AML (except M3) or high-risk MDS diagnostic criteria, with any of the following circumstances: ①secondary AML patients (including AML secondary to MDS) ②corresponding to refractory AML diagnostic standard ( relapsed refractory acute myeloid leukemia Chinese guidelines(2017 Edition): Refractory AML diagnostic criteria: invalid after standard treatment 2 cycles of untreated cases; consolidation therapy after CR and then recurrence within 12 months; recurrence after 12 months and then invalid after conventional chemotherapy ; relapse of ≥ 2 times ; extramedullary leukemia continued existence. ③corresponding to recurrent AML diagnostic criteria (relapsed refractory acute myeloid leukemia China guidelines (2017 Edition): peripheral blood leukemia cells or bone marrow progenitor cells appear again > 0.050 after CR (with the exception of bone marrow regeneration after consolidation chemotherapy and other reasons) or leukemia cells infiltration appear in extramedullary ④corresponding to MDS refractory anemia with blasts excess (RAEB) diagnosis standards Age ≥18 years old Eastern Cooperative Oncology Group(ECOG) score 0-3 Expected survival ≥8 weeks Patients must be able to understand and be willing to participate in this study, and signed informed consent Exclusion Criteria: acute promyelocytic leukemia (M3 type) Other types of MDS patients except RAEB with other advanced malignant tumors patients with uncontrolled severe infection, and can not tolerate chemotherapy with other serious underlying diseases patients with heart failure: ejection fraction (EF) < 30%, New York Heart Association(NYHA) standard, cardiac insufficiency in class II or above

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DLAAG<br>All patients receive 1-2 cycles of induction chemotherapy,that is DLAAG,which is expected to be 6 weeks/cycle,including decitabine,cytarabine, all-transretinoic acid,and Granulocyte Colony-Stimulating Factor(G-CSF). patients with CR after the first course of induction therapy (DLAAG) will continue to receive 1 cycle of consolidation therapy, while those with therapy failure will continue the second course of induction therapy. If CR is not achieved, quit the study. Patients who achieve CR after induction therapy will be in accordance with the guidelines, such as the proposed active treatment of allogeneic hematopoietic stem cell transplantation | Drug: Decitabine<br>* Decitabine,iv,0.1-0.2mg/kg, Day1-Day3 per week,up to 3 weeks<br>* Other names: Qingweike;Drug: Cytarabine<br>* cytarabine, iv,15mg/m2 q12h, Day1-Day10<br>* Other names: Cytosar;Drug: All-transretinoic acid<br>* All-transretinoic acid, 45mg/d Day4-Day6;15mg/d Day7-Day20<br>* Other names: Ailike;Drug: G-CSF<br>* G-CSF 300ug,sc,Day 0 until CR is achieved<br>* Other names: Filgrastim;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate (CR) | Morphologic CR - patient independent of transfusions Absolute neutrophil count(ANC) >1000/ Microliter(mcL) Platelets ≥100,000/mcL No residual evidence of extramedullary disease Cytogenetic CR - cytogenetics normal (in those with previously abnormal cytogenetics) Molecular CR - molecular studies negative CR with incomplete blood cells count recovery(CRi) - There are some clinical trials, particularly those that focus on the elderly or those with antecedent myelodysplasia, that include a variant of complete response referred to as CRi. This has been defined as <5% marrow blasts, either ANC <1000/mcL or platelets <100,000/mcL, and transfusion independence but with persistence of cytopenia (usually thrombocytopenia). | at the end of every course(about 4 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early death rate | The rate of early death within 30 days | the death rate after treating Day1 to Day30 | 
| Leukemia free survival (LFS) | Morphologic leukemia-free state Bone marrow <5% blasts in an aspirate with spicules No blasts with Auer rods or persistence of extramedullary disease | from enrolling to the end of 2-year following up | 
| Overall survival(OS) | The time from the date of enrolling to the date of death due to any reasons or the last following date | from enrolling to the end of 2-year following up | 
| The rate of adverse reaction the rate of adverse reaction | the rate of adverse reaction, according to Standard for World Health Organization(WHO) acute and subacute toxicity | from enrolling to the end of 2-year following up | 
| Duration of hospitalization | The time from the date of be hospitalized to the date of be discharged | from enrolling to the end of 2-year following up | 
| The rate of relapse | Relapse following complete response is defined as reappearance of leukemic blasts in the peripheral blood or the finding of more than 5% blasts in the bone marrow, not attributable to another cause (eg, bone marrow regeneration after consolidation therapy) or extramedullary relapse | from enrolling to the end of 2-year following up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
decitabine, retinoid acid, cytarabine C, Granulocyte Colony Stimulating Factor, acute myeloid leukemia, Myelodysplastic Syndrome