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)

NCT03150004 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO29327
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Keywords

Acute myeloid leukemia; AML; salvage chemotherapy; CLAG-M; relapse acute myeloid leukemia; secondary acute myeloid leukemia; phase II; pharmacogenomics; myelodysplastic syndrome

Outcome Measures

Primary Outcomes (5)

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

  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)

  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.

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

  Day 70

• Overall Survival (OS)

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

  Up to 4 Years

• 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

  Year 4

Study Arms (2)

CLAG-M regimen

EXPERIMENTAL

Subject's treatment cycle is 30 days.

Drug: Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen

CLLDAC regimen

EXPERIMENTAL

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

Interventions

Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen DRUG

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.

Also known as: Leustatin, AraC, Cytosar, Novantrone, filgastim, Neupogen, Granix, Zarxio

CLAG-M regimen

Cladribine and Cytarabine (CLLDAC) Regimen DRUG

* Cladribine 5 mg/m\^2 IV over two hours on days 1-5; * Cytarabine 20 mg/m\^2 subcutaneous injection on days 1-10;

Also known as: Leustatin, Cytosar

CLLDAC regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• 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.

  PMID: 16609072 BACKGROUND

• 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.

  PMID: 14673054 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Cladribine; Cytarabine; Mitoxantrone; Granulocyte Colony-Stimulating Factor; Clinical Protocols; Filgrastim

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Therapeutics; Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Ehab Atallah, MD
• Organization: Medical College of Wisconsin

eatallah@mcw.edu

414-805-4600

Study Officials

• Ehab Atallah, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Medicine, Division of Hematology/Oncology

Study Record Dates

• First Submitted: May 2, 2017
• First Posted: May 11, 2017
• Study Start: June 14, 2017
• Primary Completion: March 14, 2025
• Study Completion: March 14, 2025
• Last Updated: March 30, 2026
• Results First Posted: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)