Efficacy and Pharmacogenomics of Cladribine Based Salvage Chemotherapy in Patients With Relapse/Refractory and Secondary Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)

March 10, 2026 updated by: Ehab L Atallah, Medical College of Wisconsin

A Phase II Study of the Efficacy and Pharmacogenomics of Cladribine-based Salvage Chemotherapy in Patients With Relapse/Refractory and Secondary Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)

This is a prospective phase II clinical study planned to be conducted at the Medical College of Wisconsin (MCW). After meeting the study criteria and enrollment, patients will be treated with a cladribine based salvage regimen and followed at periodic intervals to determine the primary and secondary objectives.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

STUDY RATIONALE:

The optimal treatment regimen for relapsed/refractory AML and high risk MDS progressing after hypomethylating agents is unknown. Although several chemotherapy options are available, there is no universally accepted regimen to date. Cladribine based salvage regimens have been frequently used at the investigators' center. However, it is uncertain to predict which patients are likely to respond to cladribine-based salvage or experience treatment-related toxicities. While studies have demonstrated that achievement of MRD negative complete remission (CR) is likely to be associated with a better overall survival (OS), there is limited prospective data evaluating the role of minimal residual disease (MRD) in the setting of relapsed/refractory disease. Through this study, the investigators aim to demonstrate the influence of achieving MRD negative CR on survival of patients with relapsed/refractory AML/high risk MDS treated with cladribine-based salvage therapy. 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 CR rate and achievement of MRD negativity after treatment with Cladribine based salvage chemotherapy regimen in patients with relapse/refractory AML/high risk MDS.

SECONDARY OBJECTIVES:

  1. To determine the progression free survival (PFS) and overall survival (OS) of patients treated with a cladribine based salvage chemotherapy regimen.
  2. To study the pharmacogenomics of patients receiving a cladribine based salvage 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 a cladribine based salvage regimen.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
53

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Medical College of Wisconsin Clinical Cancer Center
  • Phone Number: 8900 866-680-0505
  • Email: cccto@mcw.edu

Study Locations

  • United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert & the Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 myeloproliferative neoplasm (MPN), or
    • Therapy related AML (t-AML), as defined by World Health Organization (WHO) criteria.
    • Subjects with high risk MDS after failure of hypomethylating agents are also eligible.

  3. Subjects 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
    • Subjects with MDS or MPN transformed to AML will be eligible even if they had not received prior therapy for AML.
    • Subjects with high risk MDS after failure of hypomethylating agents.
  4. Eastern Cooperative Oncology Group (ECOG) performance score 0-3.

  5. It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female subjects participating in this study should avoid becoming pregnant, and male subjects should avoid impregnating a female partner. Non- sterilized female subjects of reproductive age and male subjects should use effective methods of contraception through defined periods during and after study treatment as specified below.

    Female subjects must meet one of the following:

    • Postmenopausal for at least one year before the screening visit, or
    • Surgically sterile, or if they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through 90 days after the last dose of study drug, AND
    • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, or
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable contraception methods.)

    Male subjects, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:

    • Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, OR
    • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
  6. Ability to understand a written informed consent document and the willingness to sign it.
  7. Subjects must meet the following clinical laboratory criteria:

CLAG-M Arm Only:

For abnormalities in liver function tests, elevation thought to be due to hepatic infiltration by AML, Gilbert's syndrome or hemolysis would not be treated as exclusion criteria.

  • Absolute neutrophil count ≥1,000/mm^3 Unless related to AML
  • Platelets ≥75,000/mm^3 Unless related to AML
  • Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN) (if elevated, then complete direct bilirubin).
  • AST(SGOT)/ALT Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN
  • Creatinine clearance ≥ 30 mL/min
  • Resting left ventricular ejection fraction ≥ 45%

CLLDAC ARM ONLY:

  • Absolute neutrophil count ≥ 1,000/mm^3 unless related to AML
  • Platelets ≥ 75,000/mm^3 unless related to AML

Exclusion Criteria:

  1. Acute Promyelocytic Leukemia.
  2. Active infection not well controlled by antibacterial or antiviral therapy.
  3. Pregnant or breast feeding women.
  4. Participation in clinical trials with other investigational agents not included in this trial, throughout the duration of this trial. Participation of follow-up portion of another clinical trial will not exclude patient from participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: CLAG-M regimen
Subject's treatment cycle is 30 days.
Drug: Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen

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

  • Cladribine 5 mg/m^2 IV over two hours on days 1-5;
  • Cytarabine 2 gm/m^2 IV over four hours on days 1-5
  • Mitoxantrone 10 mg/m^2 IV on days 1-3;
  • G-CSF at a dose of 300 μg on days 0-5.
Other Names:
  • Cytosar
  • Neupogen
  • Novantrone
  • Zarxio
  • Leustatin
  • AraC
  • filgastim
  • Granix
Experimental: CLLDAC regimen
Subject's treatment cycle is 30 days. Subject may be treated on an outpatient basis (CLLDAC arm only). In addition, subjects who fail to achieve a CR/CRi after the first 30-day cycle may receive a second cycle of CLLDAC, per the discretion of the treating physician. Subjects who receive this second cycle should begin cycle 2 no later than 49 days after cycle 1.
Drug: Cladribine and Cytarabine (CLLDAC) Regimen
  • Cladribine 5 mg/m^2 IV over two hours on days 1-5;
  • Cytarabine 20 mg/m^2 subcutaneous injection on days 1-10;
Other Names:
  • Cytosar
  • Leustatin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
CLAG-M Arm: Minimal Residual Disease (MRD) Complete Remission (CR)
Time Frame: Day 35
The number of participants who achieve MRD CR (see Cheson 2003, Cheson 2006 in the references below).
Day 35
CLLDAC Arm: Minimal Residual Disease (MRD) Complete Remission (CR)
Time Frame: Day 35
The number of participants who achieve MRD CR following one cycle of therapy (see Cheson 2003, Cheson 2006 in the references below).
Day 35
CLLDAC Arm: Subjects Receiving a Second Cycle.
Time Frame: Day 70
The number of subjects who require a second cycle of CLLDAC.
Day 70
Overall Survival (OS)
Time Frame: Up to 4 Years
Duration of OS: Time from treatment initiation through death from any cause, up to 4 years
Up to 4 Years
Progression-free Survival
Time Frame: Year 4
Duration of PFS: Time from remission (date of bone marrow biopsy confirming CR/CRi) to relapse or death from any cause, whichever occurs first, up to 4 years
Year 4

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Year 4
The number of participants still alive following CLAG-M chemotherapy.
Year 4
Prediction of minimal residual disease (MRD) negativity
Time Frame: Day 5
The number of participants predicted to have no minimal residual disease, using pharmacogenomics.
Day 5
Prediction of the development of treatment-related toxicities
Time Frame: Day 5
The number of participants predicted to have treatment-related toxicities, using pharmacogenomics.
Day 5
Progression-free survival
Time Frame: Year 4
The number of participants who don't experience progressive disease.
Year 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical College of Wisconsin

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ehab Atallah, MD, Medical College of Wisconsin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 14, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 14, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 14, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 2, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 10, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 11, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 30, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRO29327

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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