HD-Idarubicin/Etoposide Intensified Conditioning Regimen Allo-HSCT for Adult ALL

Study Overview
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Brief Summary
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Intensified conditioning regimen allo-HSCT is based on a hypothesis of that intensifying condition with less-used drugs could overcome resistance,reduce tumor burden, and most importantly, spare enough time for slow-growing GVL effect following immune reconstitution to finally get rid of MRD and control the disease. Our previous trial of HDE-ALL-2011 (NCT01457040) have confirmed the role of intensified conditioning allo-HSCT in adult ALL, resulting in significantly improved OS and EFS in comparison with previous standard TBI/CY2 conditioning regimen(data not yet published). But at the same time, FA-TBI/CY2-VP16 conditioning regimen was associated with high transplantation-related mortality (TRM), which might be attributed to excessive suppression on both bone marrow and immune. TT-ALL-HIE-2013, substituting FA with idarubicin, is aimed at maintaining anti-tumor effect with less cross-resistance and immune suppression and reducing TRM.

Detailed Description
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It's well-known that the long-term outcome of adult acute lymphoblastic leukemia (ALL) lags far behind that of pediatric ALL,associated with different molecular cytogenetics make-up and treatment strategies. In search of an optimal regimen for pediatric ALL, comprehensive series of clinical trials of intensive chemotherapies have been conducted and lead to 80%-90% long-term survival. At the same time, pediatric-inspired chemotherapy protocol aslo yielded a charming result of 50-60% 3-year EFS in adolescent and young adult. In comparison with the leading role of intensive chemotherapy in pediatric ALL, allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in treatment strategy of adult ALL. According to the state-of-art understanding of ALL, total therapy of ALL should consist of molecular-cytogenetics classification at diagnosis, minimal residual disease (MRD) monitoring and redefining risk classification during treatment, pediatric-inspired chemotherapy with high-dose Methotrexate/L-asparaginase during consolidation therapy,furthermore,risk/MRD-adapted allo-HSCT for high-risk and refractory/relapsed ALL.In pre-pediatric-inspired protocol era, allo-HSCT still represents the major role for improving the outcome of adult ALL, especially for high-risk and refractory/relapsed ALL. It's established that graft-versus-leukemia (GVL) effect was weak in ALL and patient shows poor response for donor-lymphocyte infusion (DLI). Intensified conditioning regimen allo-HSCT is based on a hypothesis of that intensifying condition with less-used drugs could overcome resistance,reduce tumor burden, and most importantly, spare enough time for slow-growing GVL effect following immune reconstitution to finally get rid of MRD and control the disease. Our previous trial of HDE-ALL-2011 (NCT01457040) have confirmed the role of intensified conditioning allo-HSCT in adult ALL, resulting in significantly improved OS and EFS in comparison with previous standard TBI/CY2 conditioning regimen(data not yet published). But at the same time, FA-TBI/CY2-VP16 conditioning regimen was associated with high transplantation-related mortality (TRM), which might be attributed to excessive suppression on both bone marrow and immune. TT-ALL-HIE-2013, substituting FA with idarubicin, is aimed at maintaining anti-tumor effect with less cross-resistance and immune suppression and reducing TRM.

Official Title
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An Open-label,Multi-center,Prospective Study of Idarubicin and Etoposide Intensified Conditioning Regimen Allogeneic Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: IDA
* Radiation: TBI
* Drug: CTX
* Drug: VP-16


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 16 years to 65 years; Diagnosis of acute lymphoblastic leukemia; Patient receives allo-HSCT; The informed consent form has been signed; Exclusion Criteria: Patient with severe cardiac dysfunction with less than 50% EF; Patient with severe lung dysfunction; Patient with more than 3 times ULN of serum ALT or AST levels, or with more than 2 times ULN of serum TBIL level, or less than 40% of normal prothrombin time activity (PTA); or with more than 2 times the ULN of serum Cr; Patient with severe active infection; Patient with allergy history about suspected drug in conditioning regimen; Patient with other conditions considered unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IDA-Etoposide Intensified Conditioning<br> | Drug: IDA<br>* Idarubicin: 15mg/m2/d: -8->-6d<br>* Other names: Idarubicin;Radiation: TBI<br>* TBI: 4.5 Gy/d, -5d, -4d<br>* Other names: Total Body Irradiation;Drug: CTX<br>* CY:60mg/kg/d, -3d, -2d<br>* Other names: Cyclophosphamide;Drug: VP-16<br>* VP-16: 15mg/kg, -2d, -1d<br>* Other names: Etoposide;|
| Active Comparator: Non-IDA Conditioning<br> | Radiation: TBI<br>* TBI: 4.5 Gy/d, -5d, -4d<br>* Other names: Total Body Irradiation;Drug: CTX<br>* CY:60mg/kg/d, -3d, -2d<br>* Other names: Cyclophosphamide;Drug: VP-16<br>* VP-16: 15mg/kg, -2d, -1d<br>* Other names: Etoposide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-Free Survival |  | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplantation-Related Mortality |  | 3 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idarubicin, Etoposide, HSCT, Acute Lymphoblastic Leukemia