AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 2NCT03150004

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)

A Phase 2 study testing Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen and Cladribine and Cytarabine (CLLDAC) Regimen in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Medical College of Wisconsin at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen and Cladribine and Cytarabine (CLLDAC) Regimen
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
1 siteUnited States
Study dates
14 Jun 2017to 14 Mar 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years at the time of informed consent.
  • 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.
Show all 34Show fewer
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance score 0-3.
  • 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.)
  • Ability to understand a written informed consent document and the willingness to sign it.
  • 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

Who cannot join

  • Acute Promyelocytic Leukemia.
  • Active infection not well controlled by antibacterial or antiviral therapy.
  • Pregnant or breast feeding women.
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Froedtert & the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

Official title: 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.

Read the 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.
Being tested
Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen, Cladribine and Cytarabine (CLLDAC) Regimen
Keywords
Acute myeloid leukemia, AML, salvage chemotherapy, CLAG-M, relapse acute myeloid leukemia, secondary acute myeloid leukemia, phase II, pharmacogenomics, myelodysplastic syndrome
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimenDrug

    Also called Leustatin, AraC, Cytosar, Novantrone

    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.
  • Cladribine and Cytarabine (CLLDAC) RegimenDrug

    Also called Leustatin, Cytosar

    • Cladribine 5 mg/m^2 IV over two hours on days 1-5;
    • Cytarabine 20 mg/m^2 subcutaneous injection on days 1-10;
Study groups in NCT03150004
Study groupRoleWhat they receive
CLAG-M regimenExperimentalSubject's treatment cycle is 30 days.
Receives: Drug: Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen
CLLDAC regimenExperimentalSubject'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.
Receives: Drug: Cladribine and Cytarabine (CLLDAC) Regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CLAG-M Arm: Minimal Residual Disease (MRD) Complete Remission (CR)

    The number of participants who achieve MRD CR. CR (Complete Remission): The patient meets standard criteria for complete remission, including:

    • Bone marrow blasts <5%
    • No evidence of leukemia outside the marrow
    • Recovery of blood counts (typically ANC >1,000/μL and platelets >100,000/μL)

    MRD-negative (Measurable Residual Disease negative): multiparameter flow cytometry cannot detect residual leukemia cells.

    Measured: Day 35

  2. CLLDAC Arm: Minimal Residual Disease (MRD) Complete Remission (CR)

    The number of participants who achieve MRD CR following one cycle of therapy. CR (Complete Remission): The patient meets standard criteria for complete remission, including:

    • Bone marrow blasts <5%
    • No evidence of leukemia outside the marrow
    • Recovery of blood counts (typically ANC >1,000/μL and platelets >100,000/μL)

    MRD-negative (Measurable Residual Disease negative): multiparameter flow cytometry cannot detect residual leukemia cells.

    Measured: Day 35

  3. CLLDAC Arm: Subjects Receiving a Second Cycle.

    The number of subjects who require a second cycle of CLLDAC.

    Measured: Day 70

  4. Overall Survival (OS)

    Duration of OS: Time from treatment initiation through death from any cause, up to 4 years

    Measured: Up to 4 Years

  5. Progression-free Survival

    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. Relapsed: Bone marrow blasts ≥ 5%; or reappearance of blasts in the blood in at least 2 peripheral blood samples at least one week apart; or development of extramedullary disease. Refractory: No CR, CRh or CRi at the response landmark, ie, after 2 courses of intensive induction treatment or a defined landmark, eg, 180 d after commencing less-intensive therapy.

    Measured: Year 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2017
  2. Study start14 Jun 2017
  3. Primary completion14 Mar 2025
  4. Study completion14 Mar 2025

Why it stopped: No longer have funding support to complete the pharmacogenetics component.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03150004
Sponsor's protocol ID
PRO29327
Status last verified
Sep 2026
First submitted
2 May 2017
Last updated
21 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006 Jul 15;108(2):419-25. doi: 10.1182/blood-2005-10-4149. Epub 2006 Apr 11.

    PubMed 16609072
  • Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Lowenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9. doi: 10.1200/JCO.2003.04.036.

    PubMed 14673054

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen and Cladribine and Cytarabine (CLLDAC) Regimen in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Medical College of Wisconsin at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CLAG-M Arm: Minimal Residual Disease (MRD) Complete Remission (CR) (time frame: Day 35). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03150004, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in