Sequential Intensive Chemotherapy Followed by RIC for Refractory and Relapse AML

Study Overview
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Brief Summary
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Patients with refractory and relapse leukemia had poor outcome even with allogeneic stem cell transplantation. In our previous retrospective study, the overall survival is 14.6+/-8.8% while 90% patients eventually relapsed with marrow ablative conditioning mostly standard iv-Bu-Cy or Cy-TBI. The accumulated TRM is 29.5+/-11.5%. Thus our data suggested that the conventional transplantation approach may not be able to overcome the refractory disease. A new strategy to combined a low dose regimen following intensive chemotherapy for tumor reduction seems to be effect in both relapsed. high-risk and refractory AML or ALL. In this study, we focus on a new treatment strategy for particular refractory AML patients.

Detailed Description
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This is a single arm phase II trial to test the efficacy and feasibility of new sequential intensive chemo and transplantation approach for refractory leukemia. Patients with refractory acute myeloid or lymphoblastic leukemia are enrolled in this trial. Patients will received intensive chemotherapy including Fludarabine, cytarabine and idarubicin as (FLAG-IDA). Seven days after the chemotherapy, sequential transplantation conditioning regimen as fludarabine and busulfan will be given.

Official Title
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Sequential Intensive Chemotherapy Followed by Allogeneic Stem Cell Transplantation With Reduce-intensity Conditioning for Refractory and Relapse Acute Myeloid Leukemia in Adult Patients

Conditions
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Acute Leukemia

Intervention / Treatment
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* Drug: intensive chemo - RIC preparation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients with refractory or relapse acute myeloid leukemia not in remission after 2 cycles of induction chemotherapy early relapse (1st remission less than 6 months) not in remission after 1 cycle of re-induction chemotherapy multiple relapse age 16-60 years with inform consent no contraindication for allogeneic transplantation: active infection, allergy to FLu/Bu/CTX, liver and renal function damage HLA matched related (6/6) or unrelated donors (at least 8/10) Exclusion Criteria: age less than 18 years or over 61 years liver function/renal function damage (over 2 X upper normal range) with mental disease

Ages Eligible for Study
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Minimum Age: 16 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: intensive chemo - RIC preparation<br>The intensive chemotherapy is composed of Fludarabine 35mg/m2 D1-5, high-dose cytarabine 2g/m2 D1-5 + idarubicin (12mg/m2) D5-7. The reduced intensity preparation regimen will start 7 days after the chemotherapy with fludarabine 35mg/m2 for 5 days + iv busulfan 3.2mg/kg/day for 3 days followed by stem cell infusion 2 days later. | Drug: intensive chemo - RIC preparation<br>* The intensive chemotherapy is composed of fludarabine 35mg/m2 + high-dose cytarabine 2g/m2 D1-5 + idarubicin (12mg/m2) D5-7. The reduced intensity preparation regimen will start 7 days after the chemotherapy with fludarabine 35mg/m2 for 5 days + iv busulfan 3.2mg/kg/day for 3 days followed by stem cell infusion 2 days later.<br>* Other names: FLAG-IDA-RIC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival |  | 2-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| non-relapse mortality |  | 2-year | 
| relapse rate |  | 2-year | 
| overall survival |  | 2-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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feasibility, effective and safety, intensive chemotherapy, RIC regimen, refractory or relapse leukemia, allogeneic stem cell transplantation