Clinical trial NCT01873807: HD-Idarubicin/Etoposide Intensified Conditioning Regimen Allo-HSCT for Adult ALL
Official title: An Open-label,Multi-center,Prospective Study of Idarubicin and Etoposide Intensified Conditioning Regimen Allogeneic Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Lymphoblastic Leukemia
Keywords: Idarubicin
Etoposide
HSCT
Acute Lymphoblastic Leukemia
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2013-06-10
Enrollment: 100
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age: 16 years to 65 years;
2. Diagnosis of acute lymphoblastic leukemia;
3. Patient receives allo-HSCT;
4. The informed consent form has been signed;

Exclusion Criteria:

1. Patient with severe cardiac dysfunction with less than 50% EF;
2. Patient with severe lung dysfunction;
3. 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;
4. Patient with severe active infection;
5. Patient with allergy history about suspected drug in conditioning regimen;
6. Patient with other conditions considered unsuitable for the study.

Primary outcomes:
measure: Event-Free Survival
timeFrame: 3 year
Secondary outcomes:
measure: Transplantation-Related Mortality
timeFrame: 3 year
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Department of Hematology, Union Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: Guangzhou General Hospital of Guangzhou Military Command
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong No.2 Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Department of Hematology, Nanfang Hospital, Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Third Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Department of Hematology, 1st Guangzhou People Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Oncology-Hematology Center, 1st Affiliated Hospital, Guangzhou Medical Collgege
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan People Hospital,Guangdong
state: Guangdong
city: Nanning
country: China
facility: Department of Hematology, 1st Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Wuhan
country: China
facility: Department of Hematology, Union Hospital, Huazhong Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Department of Hematology, Tongji Hospital, Huazhong Science and Technology
state: Hubei
Study officials:
affiliation: Department of Hematologym, Nanfang Hospital, Southern Medical University, China
name: Qifa Liu, MD
role: PRINCIPAL_INVESTIGATOR
References: