Efficacy and Pharmacogenomics of Salvage CLAG-M Chemotherapy in Patients With Relapse/Refractory and Secondary Acute Myeloid Leukemia

STUDY RATIONALE:

The optimal treatment regimen for relapsed/refractory acute myeloid leukemia (AML) is
unknown. Although several chemotherapy options are available, there is no universally
accepted regimen to date. One such regimen is CLAG-M (Cladribine, Cytarabine, Mitoxantrone,
G-CSF) that has been frequently used at our center. However, it is difficult to predict which
patients are likely to respond to CLAG-M or experience treatment-related toxicities. In
patients with newly diagnosed AML, studies have demonstrated that achievement of minimal
residual disease negative CR is associated with a better overall survival. However, this has
not been clearly studied in patients with relapsed-refractory AML. Through this study, we aim
to demonstrate the influence of achieving MRD negative CR on survival of patients with
relapsed/refractory AML treated with CLAG-M. In addition to the conventionally used
predictive factors, we aim to incorporate pharmacogenomics to assess the efficacy and
toxicity of therapy.

PRIMARY OBJECTIVE:

To determine the complete remission (CR) rate and achievement of minimal residual disease
(MRD) negativity after treatment with salvage CLAG-M chemotherapy regimen in patients with
relapse/refractory and secondary AML.

SECONDARY OBJECTIVES:

1. To determine the progression free survival (PFS) and overall survival (OS) of patients
treated with CLAG-M chemotherapy regimen.

2. To study the pharmacogenomics of patients receiving CLAG-M chemotherapy and determine
its influence on survival, CR rate and MRD negativity.

3. Determination of disease- or patient-related factors that predict MRD negativity and
survival with CLAG-M.

Inclusion Criteria:

1. Age ≥18 years at the time of informed consent.

2. Morphologically documented primary Acute Myeloid Leukemia (AML) or AML secondary to
Myelodysplastic Syndrome (MDS) or therapy related AML (t-AML), as defined by World
Health Organization (WHO) criteria.

3. Patients must meet one of the following criteria:

- In first or subsequent relapse or refractory status, with or without prior
hematopoietic stem cell transplant (HSCT) OR

- Patients with MDS transformed to AML will be eligible even if they had not
received prior therapy for AML.

4. Eastern Cooperative Oncology Group (ECOG) performance score 0-2.

5. Patients must meet the following clinical laboratory criteria: Direct bilirubin ≤ 1.5
X the upper limit of the normal range (ULN), alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) ≤ 3 X ULN unless related to AML or Gilbert syndrome
or hemolysis. Calculated creatinine clearance ≥30 mL/min

6. LVEF ≥ 45%

Exclusion Criteria:

1. Acute Promyelocytic Leukemia.

2. Pregnant or breast feeding women.

3. Participation in clinical trials with other investigational agents not included in
this trial, within 14 days of the start of this trial and throughout the duration of
this trial.