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

NCT02042690 | Completed Phase 3 DMC

• 1 other identifier: ALL-13
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 5

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)

Conditions

Acute Lymphoblastic Leukemia

Keywords

Acute Lymphoblastic Leukemia; hematopoietic stem cell transplantation; chemotherapy

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

  At 2 years from study entry

Secondary Outcomes (3)

• 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

Study Arms (2)

chemotherapy

ACTIVE COMPARATOR

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

Haplo-identical HSCT

EXPERIMENTAL

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

Interventions

Haplo-identical HSCT PROCEDURE

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.

Haplo-identical HSCT

Chemotherapy DRUG

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.

Also known as: Methotrexate, arabinoside, cyclophosphamide, Epirubicin, dexamethasone, 6-mercaptopurine, Vindesin, Predisone

chemotherapy

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• acute lymphoblastic leukemia
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking University: lead
• Peking Union Medical College Hospital: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• Chinese PLA General Hospital: collaborator
• The First Affiliated Hospital of Soochow University: collaborator
• Peking University Aerospace Center Hospital: collaborator

Study Sites (5)

Aerospace Center Hospital

Beijing, Beijing Municipality, 100044, China

Location

Wuhan Union Hospital

Wuhan, Hubei, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Location

General Hospital of PLA

Beijing, China

Location

Peking Union Hospital

Beijing, China

Location

Related Publications (1)

• 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.

  PMID: 32414392 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Drug Therapy; Methotrexate; Cyclophosphamide; Epirubicin; Dexamethasone; Mercaptopurine; Vindesine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Sulfhydryl Compounds; Sulfur Compounds; Purines; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Xiao-Jun Huang, MD

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Peking University People's Hospital

Model Details: 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.

Study Record Dates

• First Submitted: November 29, 2013
• First Posted: January 23, 2014
• Study Start: July 1, 2014
• Primary Completion: February 1, 2018
• Study Completion: April 1, 2019
• Last Updated: May 29, 2019

Record last verified: 2019-05

Locations

CN (5)