Haplo-identical HSCT Versus Chemotherapy for Adult Acute Lymphoblastic Leukemia Patients

Sponsor

Peking University (Other)

Overall Status

Completed

CT.gov ID

NCT02042690

Collaborator

Peking Union Medical College Hospital (Other), Wuhan Union Hospital, China (Other), Chinese PLA General Hospital (Other), The First Affiliated Hospital of Soochow University (Other), Peking University Aerospace Centre Hospital (Other)

131

Enrollment

Locations

Arms

Actual Duration (Months)

26.2

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia	Procedure: Haplo-identical HSCT Drug: Chemotherapy	Phase 3

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

Actual Enrollment :

131 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase III Study to Compare Haplo-identical HSCT Versus Chemotherapy in First Remission for Standard-risk Adult Acute Lymphoblastic Leukemia

Actual Study Start Date :

Jul 1, 2014

Actual Primary Completion Date :

Feb 1, 2018

Actual Study Completion Date :

Apr 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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	Drug: Chemotherapy 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. Other Names: Methotrexate arabinoside cyclophosphamide Epirubicin dexamethasone 6-mercaptopurine Vindesin Predisone
Experimental: 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.	Procedure: Haplo-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.

Arm

Intervention/Treatment

Active Comparator: 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

Drug: Chemotherapy

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.

Other Names:

Methotrexate

arabinoside

cyclophosphamide

Epirubicin

dexamethasone

6-mercaptopurine

Vindesin

Predisone

Experimental: 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.

Procedure: Haplo-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.

Outcome Measures

Primary Outcome Measures

Disease-free survival [At 2 years from study entry]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 39 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aerospace Center Hospital	Beijing	Beijing	China	100044
2	Wuhan Union Hospital	Wuhan	Hubei	China
3	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China
4	General Hospital of PLA	Beijing		China
5	Peking Union Hospital	Beijing		China