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

The Affiliated Hospital of the Chinese Academy of Military Medical Sciences

Status and phase: Completed; Phase 3

Conditions: Acute Myeloid Leukemia

Treatments: Drug: cyclophosphamide; Drug: Mycophenolate mofetil; Drug: Ara-C; Drug: fludarabine; Genetic: HLA matched stem cell; Drug: cyclosporine A; Genetic: HLA mismatched stem cell; Drug: anti-lymphocyte globulin

Study type: Interventional

Funder types: Other

Identifiers

NCT02461121

MST vs NST

Details and patient eligibility

About

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.

Full 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.

Enrollment: 156 patients

Sex: All

Ages: 9 to 59 years old

Volunteers: No Healthy Volunteers

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.
• Donors exclusion criteria include:active infection or malignancy, cardiovascular instability, severe anemia, severe coagulation disorder, pregnancy, inadequate venous access, inability to provide consent, or any other condition deemed unsafe by the treatment staff.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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156 participants in 2 patient groups

MST（microtransplantation）

Experimental group

Description:

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.

Treatment:

Genetic: HLA mismatched stem cell

Drug: Ara-C

NST（nonmyeloablative transplantation）

Active Comparator group

Description:

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

Treatment:

Drug: anti-lymphocyte globulin

Drug: cyclosporine A

Genetic: HLA matched stem cell

Drug: fludarabine

Drug: Ara-C

Drug: Mycophenolate mofetil

Drug: cyclophosphamide