HLA-mismatched MST vs HLA-matched NST for AML in Intermediate-risk

NCT ID: NCT02461121

Last Updated: 2015-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2013-05-31

Brief Summary

Patients with de novo AML enrolled in the study. Patient who has a HLA-identical donor is assigned to receive NST therapy with GVHD prophylaxis and who has no HLA-identical donor is assigned to receive MST therapy without GVHD prophylaxis.

Detailed Description

The optimal therapy for intermediate-risk patients with acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. Recent studies shown that microtransplantation (MST) can improve survival in AML-CR1 patients. However, a comparison study between the MST and nonmyeloablative stem cell transplantation (NST) is lacking. 156 intermediate-risk AML-CR1 patients aged 9 to 59 years were enrolled in this study. Patients with de novo AML enrolled in the study. Patient who has a HLA-identical donor is assigned to receive NST therapy with GVHD prophylaxis and who has no HLA-identical donor is assigned to receive MST therapy without GVHD prophylaxis.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MST（microtransplantation）

The microtransplantation conditioning regimen included high-dose Ara-C chemotherapy (2.0 to 2.5 g/m2 per 12 hours intravenously on days -4 to -2) followed by an infusion of HLA mismatched stem cell 24 hours (day 0) after the completion of cytarabine.

Group Type: EXPERIMENTAL

HLA mismatched stem cell

Intervention Type: GENETIC

HLA mismatched donor G-CSF mobilized peripheral stem cell infused 24 hours (day 0) after the completion of chemotherapy

Ara-C

Intervention Type: DRUG

2.0 to 3.0g/m2 per 12 hours intravenously for 6 dose

NST（nonmyeloablative transplantation）

The NST（nonmyeloablative transplantation）conditioning regimen consisted of 30 mg/m2/d fludarabine for days -6 to -2, 1.5-2 mg/kg/d anti-lymphocyte globulin for days -5 to -2, 40 mg/kg/d cyclophosphamide for days -4 and -2 and 2.0-3.0 g/m2/d cytarabine for days -6 to -4，followed by an infusion of HLA matched stem cell after the completion of regimen. The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil

Group Type: ACTIVE_COMPARATOR

HLA matched stem cell

Intervention Type: GENETIC

HLA matched donor G-CSF mobilized peripheral stem cell infused after the conditioning reginmen

cyclosporine A

Intervention Type: DRUG

The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil

Mycophenolate mofetil

Intervention Type: DRUG

The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil

Ara-C

Intervention Type: DRUG

2.0 to 3.0g/m2 per 12 hours intravenously for 6 dose

fludarabine

Intervention Type: DRUG

30 mg/m2/d for 5days

anti-lymphocyte globulin

Intervention Type: DRUG

1.5-2 mg/kg/d for 4 days

cyclophosphamide

Intervention Type: DRUG

40 mg/kg/d for 2 days

Interventions

HLA mismatched stem cell

HLA mismatched donor G-CSF mobilized peripheral stem cell infused 24 hours (day 0) after the completion of chemotherapy

Intervention Type: GENETIC

HLA matched stem cell

HLA matched donor G-CSF mobilized peripheral stem cell infused after the conditioning reginmen

Intervention Type: GENETIC

cyclosporine A

The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil

Intervention Type: DRUG

Mycophenolate mofetil

The GVHD prophylaxis included cyclosporine A and mycophenolate mofetil

Intervention Type: DRUG

Ara-C

2.0 to 3.0g/m2 per 12 hours intravenously for 6 dose

Intervention Type: DRUG

fludarabine

30 mg/m2/d for 5days

Intervention Type: DRUG

anti-lymphocyte globulin

1.5-2 mg/kg/d for 4 days

Intervention Type: DRUG

cyclophosphamide

40 mg/kg/d for 2 days

Intervention Type: DRUG

Other Intervention Names

microtransplantation; nonmyeloablative transplantation; GVHD prophylaxis; GVHD prophylaxis; conditioning reginmen; NST conditioning reginmen; NST conditioning reginmen; NST conditioning reginmen

Eligibility Criteria

Inclusion Criteria

• Patients must have elderly (9-59 ages) AML pathologically confirmed per WHO guidelines.
• Patients WITH intermediate-risk AML-CR1
• Patients must have ECOG Performance status of 0,1,or 2. If ECOG 2.
• Patients must have a HLA mismatched donor who should be able to provide informed consent.
• All genders and races are eligible.
• ALT and AST≤3 ×ULN, TBIL≤1.5 × ULN, Cr≤2 ×ULN or CrCl≥40 mL/min
• By means of ultrasonic Heartbeat map or multiple gated acquisition (MUGA) scanning determination of LVEF in the normal range.
• Donors must be able to safely undergo leukapheresis.

Exclusion Criteria

• received operation 4 weeks before randomization
• acute promyelocytic leukemia,Myeloid sarcoma, chronic myeloid leukemia in accelerated phase and blastic phase;
• active CNS disease, pregnancy, or other major medical or psychiatric illnesses that could compromise tolerance to this protocol
• Require the use of warfarin or equivalent of vitamin K antagonists (such as phenprocoumon) anticoagulant.
• There is clinical significance of cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months before randomization, or any heart function grade 3 (moderate) or 4 (severe ) heart disease in accordance with the functional classification method of New York Heart Association (NYHA).
• Known to have the following history: human immunodeficiency virus (HIV) or active hepatitis C virus or hepatitis B virus infection
• Any situation processed by the PI that will be damaged to the patients safety.
• Patients and / or authorized family member refuse to sign the consent. attend other clinical researchers in 3 months.

• Minimum Eligible Age: 9 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Affiliated Hospital of the Chinese Academy of Military Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ai huisheng

Role: PRINCIPAL_INVESTIGATOR

Affiliated Hospital of Academy of Military Medical Sciences

Locations

Affiliated Hospital of Academy of Military Medical Sciences ,

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

MST vs NST

Identifier Type: -

Identifier Source: org_study_id