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

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Haplo-identical HSCT

Chemotherapy

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring Acute Lymphoblastic Leukemia, hematopoietic stem cell transplantation, chemotherapy

Eligibility Criteria

18 Years - 39 Years (Adult)All SexesDoes not accept 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

Sites / Locations

Aerospace Center Hospital
Wuhan Union Hospital
The First Affiliated Hospital of Soochow University
General Hospital of PLA
Peking Union Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

chemotherapy

Haplo-identical HSCT

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Disease-free survival

Secondary Outcome Measures

Rate of cumulative incidence of relapse

Overall survival (OS) rate

nonrelapse mortality

Full Information

NCT ID

NCT02042690

First Posted

November 29, 2013

Last Updated

May 27, 2019

Sponsor

Peking University

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT02042690

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Completed

Study Start Date

July 2014 (Actual)

Primary Completion Date

February 2018 (Actual)

Study Completion Date

April 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking University

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

Yes

5. 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)

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lymphoblastic Leukemia

Keywords

Acute Lymphoblastic Leukemia, hematopoietic stem cell transplantation, chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

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.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

131 (Actual)

8. Arms, Groups, and Interventions

Arm Title

chemotherapy

Arm Type

Active Comparator

Arm Description

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

Arm Title

Haplo-identical HSCT

Arm Type

Experimental

Arm Description

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 Type

Procedure

Intervention Name(s)

Haplo-identical HSCT

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Chemotherapy

Other Intervention Name(s)

Methotrexate, arabinoside, cyclophosphamide, Epirubicin, dexamethasone, 6-mercaptopurine, Vindesin, Predisone

Intervention Description

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.

Primary Outcome Measure Information:

Title

Disease-free survival

Time Frame

At 2 years from study entry

Secondary Outcome Measure Information:

Title

Rate of cumulative incidence of relapse

Time Frame

At 2 years from study entry

Title

Overall survival (OS) rate

Time Frame

At 2 years from study entry

Title

nonrelapse mortality

Time Frame

At 2 years from study entry

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

39 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xiao-Jun Huang, MD

Organizational Affiliation

Peking University People's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Aerospace Center Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100044

Country

China

Facility Name

Wuhan Union Hospital

City

Wuhan

State/Province

Hubei

Country

China

Facility Name

The First Affiliated Hospital of Soochow University

City

Suzhou

State/Province

Jiangsu

Country

China

Facility Name

General Hospital of PLA

City

Beijing

Country

China

Facility Name

Peking Union Hospital

City

Beijing

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

32414392

Citation

Lv M, Jiang Q, Zhou DB, Hu Y, Liu DH, Wu DP, Wang JB, Jiang H, Wang J, Chang YJ, Wang Y, Zhang XH, Xu LP, Liu KY, Huang XJ. Comparison of haplo-SCT and chemotherapy for young adults with standard-risk Ph-negative acute lymphoblastic leukemia in CR1. J Hematol Oncol. 2020 May 15;13(1):52. doi: 10.1186/s13045-020-00879-1.

Results Reference

derived

Acute Lymphoblastic Leukemia

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial