Phase III Study to Compare Haplo-identical HSCT Versus Chemotherapy in First Remission for Standard-risk Adult Acute Lymphoblastic Leukemia
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 131
- Locations
- 5
- Primary Endpoint
- Disease-free survival
Study Overview
Brief Summary
The survival of adult patients with standard-risk acute lymphoblastic leukemia(ALL) need to improve. We want to compare the efficacy of haplo-identical hematopoietic stem cell transplantation (HSCT) with chemotherapy for adult(age:18-39 years old) ALL patients in first phase of complete remission (CR1)
Detailed Description
Although the high complete remission rate (80%-90%) can be achieved, the long-term survival rate of standard-risk adult patients with acute lymphoblastic leukemia(ALL) is only 25%-55% when they receive chemotherapy alone. The survival rate can be further improved uo to 50%-75% when they receive HLA-matched HSCT However, the chance of finding a HLA-matched donor is low, especially in China. Alternative donor such as halpo-identical related donor might be an choice.
Our retrospective analysis showed about 59% overall survival could be achieved when standard-risk adult ALL patients received halpo-identical HSCT.Therefore, we start this randomization controlled trial to compare the efficacy of haplo-identical HSCT with chemotherapy for adult(age:18-39 years old) ALL patients in CR1.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 39 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •acute lymphoblastic leukemia
- •18-39 years old
- •in first complete remission -Adequate hepatic function defined as: total bilirubin ≤2.0 times the institutional upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase(AST) ≤2.5 times the institutional ULN -
- •Adequate renal function defined as creatinine ≤3 times the institutional ULN
- •No uncontrollable infection
- •Performance Status(PS)score 0-2(WHO)
- •Subjects able to provide written informed consent
Exclusion Criteria
- •having HLA-matched donor
- •high-risk ALL: (1)Ph+ALL (2)Hypodiploidy (3)t(v;11q23) (4) complex karyotype（≥5 chromosome abnormalities）（5）high white blood cell (WBC) count (B-ALL≥30×109/L;T-ALL ≥100×109/L).
- •pregnancy
- •Loss of ability to freely provide consent due to psychiatric or physical illness
Arms & Interventions
chemotherapy
Drugs:
Drug:Methotrexate 1g/m2 d1,IV (in the vein) , used in cycle 1,3,5 Drug:arabinoside 2-3g/m2,q12h, d2-3, IV, used in cycle 1,3,5 Drug:cyclophosphamide:300mg/m2 q12h, d1-3, IV,used in cycle 2,4,6 Drug:Epirubicin 60mg/m2.d，d4,used in cycle 2,4,6 Drug:Vindesin 4mg/d，d4，d11, IV,in cycle 2,4,6 Drug:dexamethasone 40mg/d，d1-4，d11-14, IV, in cycle 2,4,6 Drug:Methotrexate 20 mg/m2/w,po, during maintenance treatment for 2 years Drug:6-mercaptopurine 60 mg/m2/d，po，d1-d28,during maintenance treatment for 2 years Drug:Vindesin 4mg/d，Predisone:1mg/kg, d1-7, every month during maintenance treatment for 2 years
Intervention: Chemotherapy (Drug)
Haplo-identical HSCT
Haplo-identical HSCT Protocol:G, donor treatment with recombinant granulocyte colony-stimulating factor (rhG-CSF); I, intensified immunologic suppression; A, antihuman thymocyte immunoglobulin (ATG) for the prevention of GVHD; C, combination of peripheral blood stem cell transplantation (PBSCT), and bone marrow transplantation (BMT)，named GIAC regimen. Graft versus-host disease(GVHD) prevention regimen: CSA/MMF/MTX, cyclosporine A(CSA) 1.25mg/kg/d, i.v administrated in two doses from day -109 until bowel function returned to normal, at which time patients receive oral CSA until 12months after HSCt and then gradually tapered. Every 12h, 0.5g mycophenolate mofetil (MMF)(0.25g for children) was administrated orally from day -10 to +30 and subsequently 0.25g from days +30 to +60. Methotrexate (MTX) was administrated at a dose of 15mg/m2 on day +1 and 10mg/m2 on days +3,+6, and +11.
Intervention: Haplo-identical HSCT (Procedure)
Outcomes
Primary Outcomes
Disease-free survival
Time Frame: At 2 years from study entry
Secondary Outcomes
- Overall survival (OS) rate(At 2 years from study entry)
- nonrelapse mortality(At 2 years from study entry)
- Rate of cumulative incidence of relapse(At 2 years from study entry)
Investigators
Xiao-jun Huang,MD
Peking University People's Hospital
Peking University