HD-Idarubicin/Etoposide Intensified Conditioning Regimen Allo-HSCT for Adult ALL
- Conditions
- Acute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT01873807
- Lead Sponsor
- Nanfang Hospital, Southern Medical University
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 100
- Age: 16 years to 65 years;
- Diagnosis of acute lymphoblastic leukemia;
- Patient receives allo-HSCT;
- The informed consent form has been signed;
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description IDA-Etoposide Intensified Conditioning CTX - IDA-Etoposide Intensified Conditioning VP-16 - Non-IDA Conditioning TBI - Non-IDA Conditioning CTX - Non-IDA Conditioning VP-16 - IDA-Etoposide Intensified Conditioning IDA - IDA-Etoposide Intensified Conditioning TBI -
- Primary Outcome Measures
Name Time Method Event-Free Survival 3 year
- Secondary Outcome Measures
Name Time Method Transplantation-Related Mortality 3 year
Trial Locations
- Locations (13)
Department of Hematology, Union Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
Guangzhou General Hospital of Guangzhou Military Command
🇨🇳Guangzhou, Guangdong, China
Guangdong General Hospital
🇨🇳Guangzhou, Guangdong, China
Department of Hematology, Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Guangdong No.2 Provincial People's Hospital
🇨🇳Guangzhou, Guangdong, China
Third Affiliated Hospital, Sun Yat-Sen University
🇨🇳Guangzhou, Guangdong, China
Department of Hematology, 1st Guangzhou People Hospital
🇨🇳Guangzhou, Guangdong, China
Oncology-Hematology Center, 1st Affiliated Hospital, Guangzhou Medical Collgege
🇨🇳Guangzhou, Guangdong, China
Zhujiang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Zhongshan People Hospital,Guangdong
🇨🇳Zhongshan, Guangdong, China
Department of Hematology, 1st Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Department of Hematology, Union Hospital, Huazhong Science and Technology
🇨🇳Wuhan, Hubei, China
Department of Hematology, Tongji Hospital, Huazhong Science and Technology
🇨🇳Wuhan, Hubei, China