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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03150004
Recruitment Status : Recruiting
First Posted : May 11, 2017
Last Update Posted : April 1, 2021
Information provided by (Responsible Party):
Ehab L Atallah, Medical College of Wisconsin

Brief Summary:
This is a prospective phase II clinical study to be conducted at the Medical College of Wisconsin. After meeting the study criteria and enrollment, patients will be treated with Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) chemotherapy and followed at periodic intervals to determine the primary and secondary objectives.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen Phase 2

Detailed Description:


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.


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.


  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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Pharmacogenomics of Salvage CLAG-M Chemotherapy in Patients With Relapse/Refractory and Secondary Acute Myeloid Leukemia
Actual Study Start Date : June 14, 2017
Estimated Primary Completion Date : October 1, 2027
Estimated Study Completion Date : October 1, 2029

Arm Intervention/treatment
Experimental: CLAG-M regimen
Patients' treatment cycle is 30 days.
Drug: Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen

Patients will be started on CLAG-M regimen, which consists of the following:

  • Cladribine 5mg/m2 IV over two hours on days 1-5;
  • Cytarabine 2 gm/m2 IV over four hours on days 1-5, starting two hours after the Cladribine infusion is complete;
  • Mitoxantrone 10mg/m2 IV on days 1-3;
  • G-CSF at a dose of 300 μg on days 0-5.
Other Names:
  • Mavenclad
  • Leustatin
  • AraC
  • Cytosar
  • Novantrone
  • filgastim
  • Neupogen
  • Granix
  • Zarxio

Primary Outcome Measures :
  1. Minimal residual disease (MRD) complete remission (CR) rate [ Time Frame: Day 35 ]
    The number of participants who achieve MRD CR. Repeat bone marrow study will be obtained after the completion of CLAG-M therapy at day 30 or when absolute neutrophil count (ANC) recovers to >1000 cells/^3.

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Year 4 ]
    The number of participants still alive following CLAG-M chemotherapy.

  2. Prediction of minimal residual disease (MRD) negativity [ Time Frame: Day 5 ]
    The number of participants predicted to have no minimal residual disease, using pharmacogenomics.

  3. Prediction of the development of treatment-related toxicities [ Time Frame: Day 5 ]
    The number of participants predicted to have treatment-related toxicities, using pharmacogenomics.

  4. Progression-free survival [ Time Frame: Year 4 ]
    The number of participants who don't experience progressive disease.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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. Left ventricular ejection fraction (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03150004

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Contact: Medical College of Wisconsin Clinical Cancer Center 414-805-8900

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United States, Wisconsin
Froedtert & the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Ehab Atallah, MD    414-805-4600   
Sponsors and Collaborators
Medical College of Wisconsin
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Principal Investigator: Ehab Atallah, MD Medical College of Wisconsin
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Responsible Party: Ehab L Atallah, Professor, Department of Medicine, Division of Hematology/Oncology, Medical College of Wisconsin Identifier: NCT03150004    
Other Study ID Numbers: PRO29327
First Posted: May 11, 2017    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Ehab L Atallah, Medical College of Wisconsin:
Acute myeloid leukemia
salvage chemotherapy
relapse acute myeloid leukemia
secondary acute myeloid leukemia
phase II
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Pathologic Processes
Disease Attributes
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors