Efficacy of Idarubicin, Cytarabine and Cyclophosphamide (IAC) Regimen in Relapsed/Refractory AML

Study Overview
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Brief Summary
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In this multi-center, randomized, open-label, prospective clinical trial, a total of 60 relapsed/refractory AML patients will be randomized into 2 groups. In the experimental arm, patients receive IAC regimen. In the control arm, patients receive other physician-directed regimen. The primary end point is complete remission rate.

Detailed Description
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In this multi-center, randomized, open-label, prospective clinical trial, a total of 60 relapsed/refractory AML patients will be randomized into 2 groups. Patients in the IAC arm receive the therapy consisting of idarubicin 10 mg/㎡/d on days 1-3, cytarabine 100mg/㎡/d on days 1-7 and cyclophosphamide at a dose of 350mg/㎡/d on the second day and the fifth day. In the control arm, patients received other physician-directed regimen including fludarabine, cytarabine with/without granulocyte stimulating factor(FLA±G) regimen,cytarabine plus daunorubicin(DA）regimen , decitabine,aclacinomycin and cytarabine(decitabine plus AA) regimen or AA regimen plus granulocyte stimulating factor. All the regimen in the control arm can not contain cyclophosphamide. The primary end point is complete remission. The second end points include overall survival, relapse-free survival and time to treatment failure.

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Idarubicin
* Drug: Cytarabine
* Drug: Cyclophosphamide
* Drug: Physician-Directed Regimens without Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of less than 60 years old; Patients that meet the diagnostic criteria(WHO 2008 criteria) of AML (except APL subtypes). Patients with a confirmed pathologic diagnosis of AML which had relapsed or refractory. Patients with ECOG score of ≤ 2; Adult patients are willing to participate in the study and sign the informed consent by themselves or by their immediate family. Patients under 18 years old willing to participate should have their legal guardians sign the informed consent. Exclusion Criteria: Patients who had received reinduction therapy including cyclophosphamide are excluded. However, patients who had received regimens including cyclophosphamide before relapse are eligible. Patients with other blood diseases(for example, haemophiliacs) are excluded. Relapsed patients with only extramedullary leukemia; After allogeneic hematopoietic stem cell transplantation; With mutation of breakpoint cluster region-Abelson(BCR-ABL) fusion gene and in need of tyrosine kinase inhibitors therapy; Acute panmyelosis with myelofibrosis and myeloid sarcoma patients; Had other malignant tumor in need of treatment; Had active cardiovascular disease; Patients with other factors which were considered unsuitable to participate in the study by the investigators.

Ages Eligible for Study
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Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IAC regimen<br>Patients receive IAC regimen including idarubicin, cytarabine and cyclophosphamide. | Drug: Idarubicin<br>* Idarubicin at a dose of 10 mg/㎡/d on days 1-3.<br>Drug: Cytarabine<br>* Cytarabine at a dose of 100mg/㎡/d on days 1-7.<br>* Other names: Ara-c;Drug: Cyclophosphamide<br>* Cyclophosphamide at a dose of 350mg/㎡/d on the second day and the fifth day.<br>* Other names: CTX;|
| Active Comparator: Control Group<br>Patients receive physician-directed regimens without cyclophosphamide including FLA±G regimen, AAG regimen, decitabine with AA regimen. Physicians can choose one of these regimens based on their experience and patients' condition. | Drug: Physician-Directed Regimens without Cyclophosphamide<br>* Regimen without cyclophosphamide including FLA±G regimen, DA regimen, AAG regimen, decitabine with AA regimen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate |  | Within 6 weeks after induction therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival(OS) | OS is defined as the time from the date of randomization until the date of death from any cause. | Up to 3 years | 
| Relapse-Free Survival(RFS) | RFS is defined as the time from the date of complete remission (CR) after entry in this trial until the date of documented relapse or death for subjects who achieve CR. | Up to 3 years | 
| Time to Treatment Failure(TTF) | TTF is defined as the time from the date of randomization until the date of death before response evaluation, not achieving CR or incomplete remission(CRi), or relapse/death after CR/CRi. | Up to 3 years |