HITA: HD-Idarubicin/Etoposide Intensified Conditioning Regimen Allo-HSCT for Adult ALL
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IDA-Etoposide Intensified Conditioning
|
Drug: IDA
Idarubicin: 15mg/m2/d: -8->-6d
Other Names:
Radiation: TBI
TBI: 4.5 Gy/d, -5d, -4d
Other Names:
Drug: CTX
CY:60mg/kg/d, -3d, -2d
Other Names:
Drug: VP-16
VP-16: 15mg/kg, -2d, -1d
Other Names:
|
| Active Comparator: Non-IDA Conditioning
|
Radiation: TBI
TBI: 4.5 Gy/d, -5d, -4d
Other Names:
Drug: CTX
CY:60mg/kg/d, -3d, -2d
Other Names:
Drug: VP-16
VP-16: 15mg/kg, -2d, -1d
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Event-Free Survival [3 year]
Secondary Outcome Measures
- Transplantation-Related Mortality [3 year]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Hematology, Union Hospital of Fujian Medical University | Fuzhou | Fujian | China | |
| 2 | Guangzhou General Hospital of Guangzhou Military Command | Guangzhou | Guangdong | China | 510010 |
| 3 | Guangdong General Hospital | Guangzhou | Guangdong | China | 510030 |
| 4 | Guangdong No.2 Provincial People's Hospital | Guangzhou | Guangdong | China | 510317 |
| 5 | Department of Hematology, Nanfang Hospital, Southern Medical University | Guangzhou | Guangdong | China | 510515 |
| 6 | Third Affiliated Hospital, Sun Yat-Sen University | Guangzhou | Guangdong | China | 510630 |
| 7 | Department of Hematology, 1st Guangzhou People Hospital | Guangzhou | Guangdong | China | |
| 8 | Oncology-Hematology Center, 1st Affiliated Hospital, Guangzhou Medical Collgege | Guangzhou | Guangdong | China | |
| 9 | Zhujiang Hospital of Southern Medical University | Guangzhou | Guangdong | China | |
| 10 | Zhongshan People Hospital,Guangdong | Zhongshan | Guangdong | China | 528403 |
| 11 | Department of Hematology, 1st Affiliated Hospital of Guangxi Medical University | Nanning | Guangxi | China | 530021 |
| 12 | Department of Hematology, Union Hospital, Huazhong Science and Technology | Wuhan | Hubei | China | 430022 |
| 13 | Department of Hematology, Tongji Hospital, Huazhong Science and Technology | Wuhan | Hubei | China | 430030 |
Sponsors and Collaborators
- Nanfang Hospital of Southern Medical University
Investigators
- Principal Investigator: Qifa Liu, MD, Department of Hematologym, Nanfang Hospital, Southern Medical University, China
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- HIE-ALL-2013