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

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

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

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Decitabine; Drug: Cytarabine; Drug: All-transretinoic acid; Drug: G-CSF

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ligen Liu; Phone Number: 18017337037; Email: llg3532@shtrhospital.com

Study Locations

• China
  • Beijing, China
    • Not yet recruiting
    • Beijing Friendship Hospital
  • Fuzhou, China
    • Not yet recruiting
    • Fujian Medical University Union Hospital
  • Nanning, China
    • Not yet recruiting
    • The People's Hospital of Guangxi Zhuang Autonomous Region
  • Shanghai, China
    • Recruiting
    • Shanghai Tong Ren Hospital
    • Contact: Ligen Liu; Phone Number: 18017337037; Email: llg3532@shtrhospital.com
  • Shanghai, China
    • Not yet recruiting
    • The center hospital of Shanghai Fengxian District
  • Zhengzhou, China
    • Not yet recruiting
    • First Affiliated Hospital of Zhengzhou University.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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

2. Age ≥18 years old
3. Eastern Cooperative Oncology Group(ECOG) score 0-3
4. Expected survival ≥8 weeks
5. Patients must be able to understand and be willing to participate in this study, and signed informed consent

Exclusion Criteria:

1. acute promyelocytic leukemia (M3 type)
2. Other types of MDS patients except RAEB
3. with other advanced malignant tumors
4. patients with uncontrolled severe infection, and can not tolerate chemotherapy with other serious underlying diseases
5. patients with heart failure: ejection fraction (EF) < 30%, New York Heart Association(NYHA) standard, cardiac insufficiency in class II or above

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: DLAAG; 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; Decitabine,iv,0.1-0.2mg/kg, Day1-Day3 per week,up to 3 weeks; Other Names: Qingweike; Drug: Cytarabine; cytarabine, iv,15mg/m2 q12h, Day1-Day10; Other Names: Cytosar; Drug: All-transretinoic acid; All-transretinoic acid, 45mg/d Day4-Day6;15mg/d Day7-Day20; Other Names: Ailike; Drug: G-CSF; G-CSF 300ug,sc,Day 0 until CR is achieved; 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

Collaborators and Investigators

• Sponsor: Shanghai Tong Ren Hospital
• Investigators: Principal Investigator: Ligen Liu, Shanghai Tong Ren Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2017
• Primary Completion (Anticipated): July 7, 2019
• Study Completion (Anticipated): July 7, 2020

Study Registration Dates

• First Submitted: November 9, 2017
• First Submitted That Met QC Criteria: November 22, 2017
• First Posted (Actual): November 29, 2017

Study Record Updates

• Last Update Posted (Actual): November 29, 2017
• Last Update Submitted That Met QC Criteria: November 22, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Myelodysplastic Syndrome; acute myeloid leukemia; decitabine; Granulocyte Colony Stimulating Factor; retinoid acid; cytarabine C
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Keratolytic Agents; Decitabine; Cytarabine; Tretinoin
• Other Study ID Numbers: DLAAG

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No