Acute Lymphoblastic Leukemia
Conditions
Keywords
Acute Lymphoblastic Leukemia, hematopoietic stem cell transplantation, chemotherapy
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.
Interventions
PROCEDUREHaplo-identical HSCT
Haplo-identical Protocol: myeloablative human leukocyte antigen (HLA) haploidentical stem cell transplantation (haplo-SCT) using pretransplant ATG and granulocyte colony-stimulating factor (G-CSF)-stimulated grafts (ATG+G-CSF) GVHD prevention regimen: CSA/MMF/MTX, 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 HRD-HSC and then gradually tapered. Every 12h, 0.5g MMF(0.25g for children) was administrated orally from day -10 to +30 and subsequently 0.25g from days +30 to +60. MTX was administrated at a dose of 15mg/m2 on day +1 and 10mg/m2 on days +3,+6, and +11.
DRUGChemotherapy
Patients receive 6 cycles of consolidation chemotherapy after randomization, including Hyper-CVAD-B regimen-Hyper-CVAD-A regimen/Hyper-CVAD-B regimen/Hyper-CVAD-A regimen/Hyper-CVAD-B regimen/Hyper-CVAD-A regimen.Maintenance treatment includes MTX 20mg/m2/w，po，6-mercaptopurine 60 mg/m2/d，po，d1-d28，VP（VDS 4mg,d1, Prednisone 1mg/kg d1-7) every one month for 2 years.
Sponsors
Peking Union Medical College Hospital
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Chinese PLA General Hospital
The First Affiliated Hospital of Soochow University
Peking University Aerospace Center Hospital
Peking University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
After 1 year of enrollment, randomization was terminated because of the patients's intention to crossover between the two intervention groups (total enrolled n=16). The sample size was recalculated in July 2015, and the ethics committee agreed to modify the randomization scheme to intention-to-therapy (ITT). Patients who met the recruitment criteria after the second consolidation participated fully in discussions with their doctors and then made decisions on their own regarding their intention to receive haplo-SCT. For each patient, informed consent was obtained from that patient or his/her guardian in accordance with the Declaration of Helsinki.
Eligibility
Sex/Gender
ALL
Age
18 Years to 39 Years
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease-free survival | At 2 years from study entry |
Secondary
| Measure | Time frame |
|---|---|
| Rate of cumulative incidence of relapse | At 2 years from study entry |
| Overall survival (OS) rate | At 2 years from study entry |
| nonrelapse mortality | At 2 years from study entry |
Countries
China
Outcome results
None listed