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

Acute Lymphoblastic Leukemia Clinical Trial

— HITA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01873807
• Other study ID #: HIE-ALL-2013
• Status: Recruiting
• Phase: Phase 4
• First received: June 6, 2013
• Last updated: October 7, 2015
• Start date: May 2013
• Est. completion date: December 2015

Study information

• Verified date: October 2015
• Source: Nanfang Hospital of Southern Medical University
• Contact: Hongsheng Zhou, PhD MD
• Phone: 86-20-62787883
• Email: hanson2008[@]gmail.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• IDA
Idarubicin: 15mg/m2/d: -8->-6d

Radiation:
• TBI
TBI: 4.5 Gy/d, -5d, -4d

Drug:
• CTX
CY:60mg/kg/d, -3d, -2d
• VP-16
VP-16: 15mg/kg, -2d, -1d

Locations

Country	Name	City	State
China	Department of Hematology, Union Hospital of Fujian Medical University	Fuzhou	Fujian
China	Department of Hematology, 1st Guangzhou People Hospital	Guangzhou	Guangdong
China	Department of Hematology, Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Guangdong No.2 Provincial People's Hospital	Guangzhou	Guangdong
China	Guangzhou General Hospital of Guangzhou Military Command	Guangzhou	Guangdong
China	Oncology-Hematology Center, 1st Affiliated Hospital, Guangzhou Medical Collgege	Guangzhou	Guangdong
China	Third Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong
China	Zhujiang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Department of Hematology, 1st Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Department of Hematology, Tongji Hospital, Huazhong Science and Technology	Wuhan	Hubei
China	Department of Hematology, Union Hospital, Huazhong Science and Technology	Wuhan	Hubei
China	Zhongshan People Hospital,Guangdong	Zhongshan	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-Free Survival		3 year	No
Secondary	Transplantation-Related Mortality		3 year	No

External Links

•   Website of Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.