Study of Decitabine Combined With HAAG Regimen in Newly Diagnosed ETP-ALL/LBL, T/M-MPAL and ALL/LBL With Myeloid or Stem Cell Markers Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of decitabine combined with HAAG regimen in the treatment of newly diagnosed patients with ETP-ALL/LBL, T/M-MPAL and ALL/LBL with myeloid or stem cell markers.

Detailed Description
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This is a phase 3, open label, single arm, multi-center study in newly diagnosed ETP-ALL/LBL, T/M-MPAL and ALL/LBL patients who have myeloid or stem cell markers. The patients will receive decitabine combined with HAAG regimen in the induction treatment. The patients who respond to induction chemotherapy will undergo consolidation chemotherapy, and an optional allogeneic hematopoietic stem cell transplantation and post-transplantation maintenance treatment with decitabine according to patient's wishes.

Official Title
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A Phase 3, Open Label, Single Arm, Multi-Center Study to Evaluate the Efficacy and Safety of Decitabine Combined With HAAG Regimen in Newly Diagnosed ETP-ALL/LBL, T/M-MPAL and ALL/LBL With Myeloid or Stem Cell Markers Patients

Conditions
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Induction Chemotherapy, Acute T-Lymphocytic Leukemia, T-cell Lymphoblastic Lymphoma Leukemia, T-cell/Myeloid Mixed Phenotype Acute Leukemia

Intervention / Treatment
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* Drug: Decitabine combined with HAAG Regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed ETP-ALL/LBL, T/M-MPAL according to the 2016 revision to the WHO classification of myeloid neoplasms and acute leukemia, and T-ALL/LBL with one or more of the myeloid or stem cell markers (CD34, CD117, HLADR, CD13, CD33, CD11b or CD65) on at least 25% of lymphoblasts. Age 15-60. Eastern Cooperative Oncology Group (ECOG) score: 0-2. No history of previous chemotherapy or target therapy. Provide informed consent. Exclusion Criteria: Patients with another malignant disease. Patients has participated in or participating in other clinical trials. Patients with uncontrolled active infection. Patients with left ventricular ejection fraction < 0.5 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification. Patients with aspartate aminotransferase or glutamic-pyruvic transaminase > 3x upper limit of normal or bilirubin > 2.0 mg/dL. Patients with creatinine clearance rate < 50ml/min. Patients with active hepatitis B or hepatitis C infection. Patients with HIV infection. Patients with active tuberculosis infection. Patients with uncontrolled active bleeding. Patients with a history of allergy to experimental drugs. Patients with other commodities that the investigators considered not suitable for the enrollment.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Decitabine combined with HAAG Regimen<br>This cohort will determine the safety and efficacy of decitabine combined with HAAG regimen in the newly diagnosed T-ALL/LBL and T/M-MPAL patients. | Drug: Decitabine combined with HAAG Regimen<br>* Decitabine :20mg/m2/d,d1 5, intravenous infusion; Homoharringtonine :1mg/d,d3 16,intravenous infusion; Aclarubicin :10mg/d, d3 d10, intravenous infusion; Cytarabine :10mg/m2,q12h,d3-16, subcutaneous injection; Granulocyte colony-stimulating factor (G-CSF): 50-300μg/d (when WBC counts are less than 20×10^9/L ),subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR includes complete remission (CR), CR with incomplete hematologic recovery (CRi) and partial remission (PR). CR was defined as < 5% bone marrow blasts in an aspirate with spicules and independent of transfusions; CRi: was defined as<5% bone marrow blasts, either ANC<1×10^9/L or platelets<100×10^9/L, transfusion independence but with persistence of cytopenia; PR was defined as decrease of at least 50% in the percentage of blasts to 5-25% in the bone marrow aspirate and the normalization of blood counts. | Day 28-35 of induction course | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | time from randomization to death from any cause | 4 years | 
| Leukemia-free survival (LFS) | time from randomization to the first relapse or death | 4 years | 
| Cumulative incidence of relapse(CIR) | time from achievement of a remmission to the first relapse | 4 years | 
| Number of adverse events | adverse events are evaluated with CTCAE V5.0. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T-ALL/LBL, T/M-MPAL, Decitabine combined with HAAG