Modified TBF Regimen as Conditioning Regimen Prior to Allo-HSCT for T-ALL/LBL
Study Details
Study Description
Brief Summary
T cell acute lymphoblastic leukemia (T-ALL)/Lymphoblastic lymphoma (LBL) is a hematological malignancy caused by malignant transformation and clonal expansion of T-lineage precursor cells. The long-term cure rate of pediatric patients with T-ALL/LBL reaches 90%, but long-term survival of adult patients is less than 60%. Moreover, patients with high-risk factors such as PTEN/NRAS gene mutation, early T cell precursor (ETP) phenotype or positive minimal residual disease (MRD) have high rates of chemoresistance and dismal outcome. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can significantly improve the prognosis of high-risk T-ALL/LBL. Total body irradiation (TBI)-based conditioning chemotherapy regimen is the preferred regimen for allo-HSCT in children and young adults with ALL because of lower relapse rates and satisfactory survival. Different from children, the non-relapse-related mortality (NRM) after TBI-based preconditioning in adults (especially those >35 years old) was reported as high as 38%. In addition, serious sequelae after TBI seriously affect the quality of life and non-radiation conditioning chemotherapy regimens are urgently needed for T-ALL/LBL. The reported recurrence rates after BUCY (busulfan + cyclophosphamide) conditioning regimen for T-ALL as 41.2%. -56.7% and long-term survival was only 30-50%. Thiotepa is an ethyleneimine alkylating agent with anti-tumor effects and immunosuppressive effects, thus is widely used in conditioning regimen before HSCT. Retrospective paired analysis from EBMT indicated conditioning regimen thiotepa achieved similar relapse rates, long-term survival and faster granulocyte and platelet engraftment than TBI regimen. A recent retrospective study of childhood ALL from Turkey also reported that the TBF(thiotepa + fludarabine + busulfan) regimen had a recurrence rate of only 11.9% , a non-relapse mortality rate of 14.0% and a long-term survival of 79.1%. Data from a large retrospective paired study suggested TBF regimen can significantly reduce the relapse rate of acute myeloid leukemia after the first remission (HR=0.4, CI 0.2-0.7, P = .02) without increasing treatment related deaths compared with the traditional BUCY regimen. Based on these data, we modified the TBF regimen with additional cytarabine for allo-HSCT in T-ALL/LBL with expection to reduced disease relapse and improved long-term survival.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Modified TBF Conditioning Regimen thiotepa 5mg/kg/d d-9 to d-8, cytarabine 0-4.0 g/m2/d d-7 to d-6(adjusted according to patients' age and HCT-CI index), fludarabine 30mg/m2/d d-7 to d-3, busulfan 3.2mg/m2/d d-5 to d-3 |
Drug: cytarabine+thiotepa+ fludarabine + busulfan
cytarabine+thiotepa+ fludarabine + busulfan intravenous injection
|
Outcome Measures
Primary Outcome Measures
- Disease free survival [2 year]
2-year DFS
Secondary Outcome Measures
- incidence of toxic reaction [2 year]
2-year incidence of toxic reaction
- overall survival [2 year]
2-year OS
- umulative incidence of relapse [2 year]
2-year incidence of relapse
- ncidence of acute and or chronic graft verus host disease [2 year]
2-year incidence of cGVHD
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age younger than 65 years
-
Patients diagnosed with T cell acute lymphoblastic leukemia/lymphoma , T-ALL/LBL according to WHO diagnostic criteria.
-
Patients who have donors and plane to accept allogeneic hematopoietic stem cell transplantation treatment.
-
ECOG body status score 0-2.
-
Good organ function level: ANC (neutrophil absolute value >=1.0x10^9/ L; PLT
=30x10^9/L; HB >=80g/L; Tibil <=1.5 ULN; ALT / AST <=2.5 ULN; bun / Cr <=1.5 ULN; LVEF >=50%).
- Patients who voluntarily participate in the clinical trial, understand the research procedure and can sign the informed consent in writing.
Exclusion Criteria:
-
Patients who with severe cardiac insufficiency, cardiac ejection fraction EF is less than 60%; or severe arrhythmia, the investigator can not tolerate conditioning chemotherapy;
-
In patients with severe pulmonary insufficiency (obstructive and / or restrictive ventilation disorders), the researchers evaluated the patients who could not tolerate conditioning chemotherapy;
-
Patients with severe liver function impairment and liver function indexes (alt, TBIL) more than 3 ULN were evaluated as intolerant of conditioning chemotherapy;
-
In patients with severe renal insufficiency, the renal function index (CR) is more than 2 times of the upper limit of the normal value (ULN), or the 24-hour creatinine clearance rate (CR) is less than 50ml / min, the researchers evaluated that they could not tolerate conditioning chemotherapy;
-
In patients with severe active infection, the researchers evaluated that they could not tolerate conditioning chemotherapy;
-
Patients who had allergic reactions or serious adverse reactions in the previous use of pretreatment related drugs could not be included in the study.
-
Other reasons why the researchers could not be selected.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated Hospital, College of Medicine, Zhejiang University | Hangzhou | China |
Sponsors and Collaborators
- First Affiliated Hospital of Zhejiang University
Investigators
- Principal Investigator: Yi Luo, M.D., First Affilaated Hospital of Medical School of Zhejiang University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ZJU-HSCT-MTBF