CPX-351 or CLAG-M Regimen for the Treatment of Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms in Medically Less-Fit Patients

NCT04195945 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1005577NCI-2019-0764010330
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well CPX-351 or the CLAG-M regimen (consisting of the drugs cladribine, cytarabine, G-CSF, and mitoxantrone) works in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms. Drugs used in chemotherapy, such as CPX-351, cladribine, cytarabine, G-CSF, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CPX-351 or the CLAG-M regimen at doses typically used for medically-fit patients with acute myeloid leukemia may work better than reduced doses of CPX-351 in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms.

Conditions

Acute Myeloid Leukemia; Myeloid Neoplasm

Keywords

Myeloid and Monocytic Leukemia; Other Hematopoietic

Outcome Measures

Primary Outcomes (1)

• 3-month overall survival (OS)

  Will evaluate whether CPX-351 or cladribine, cytarabine, granulocyte colony-stimulating factor (G-CSF), and mitoxantrone (CLAG-M), at doses typically used for medically-fit adults with AML, improve 3-month overall survival in medically-unfit adults with AML compared to attenuated dose CPX-351 as used in our previous institutional trial (32 units/m2 per dose).

  Up to 3 months from date of start of protocol therapy

Secondary Outcomes (9)

• Complete remission (CR) rates

  Up to 5 years post treatment

• MRDneg CR rates

  Up to 5 years post treatment

• Response duration

  Up to 5 years post treatment

• Relapse-free survival

  Up to 5 years post treatment

• Incidence of adverse events

  Up to 5 years post treatment

Study Arms (2)

Arm I (CPX-351)

EXPERIMENTAL

INDUCTION: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients who achieve a response other than an MRDneg CR receive a second course of CPX-351 intravenously IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. POST-REMISSION: Patients who achieve a CR/CRi receive a reduced dose of CPX-351 IV over 90 minutes on days 1, 3, and 5 for up to 4 additional courses in the absence of disease progression or unacceptable toxicity.

Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Other: Questionnaire Administration; Other: Quality-of-Life Assessment

Arm II (CLAG-M)

EXPERIMENTAL

INDUCTION: Patients receive cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, G-CSF SC on days 0-5, and mitoxantrone IV over 60 minutes on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients who achieve a response other than an MRDneg CR receive a second course of cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, G-CSF SC on days 0-5, and mitoxantrone IV over 60 minutes on days 1-3 in the absence of disease progression or unacceptable toxicity. POST-REMISSION: Patients who achieve a CR/CRi receive an intermediate dose of cytarabine IV over 2 hours on days 1-6 for up to 4 additional courses in the absence of disease progression or unacceptable toxicity.

Drug: Cladribine; Drug: Cytarabine; Biological: Recombinant Granulocyte Colony-Stimulating Factor; Drug: Mitoxantrone; Other: Questionnaire Administration; Other: Quality-of-Life Assessment

Interventions

Liposome-encapsulated Daunorubicin-Cytarabine DRUG

Given IV

Also known as: CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos, Daunorubicin and Cytarabine (Liposomal)

Arm I (CPX-351)

Cladribine DRUG

Given IV

Also known as: 105014, 105014-F, 2-Chloro-2-Deoxyadenosine, 2-Chlorodeoxyadenosine, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251

Arm II (CLAG-M)

Cytarabine DRUG

Given IV

Also known as: ARA-cell, Arabine, Arabinofuranosylcytosine, Aracytidine, Beta-Cytosine Arabinoside, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920

Arm II (CLAG-M)

Recombinant Granulocyte Colony-Stimulating Factor BIOLOGICAL

Given SC

Also known as: 143011-72-7, Recombinant Colony-Stimulating Factor 3, rhG-CSF

Arm II (CLAG-M)

Mitoxantrone DRUG

Given IV

Also known as: Dihydroxyanthracenedione, Mitozantrone

Arm II (CLAG-M)

Questionnaire Administration OTHER

Ancillary studies

Arm I (CPX-351); Arm II (CLAG-M)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (CPX-351); Arm II (CLAG-M)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of untreated "high-grade" myeloid neoplasm (\>=10% blasts in blood or bone marrow) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification. Outside diagnostic material is acceptable to establish diagnosis; submission of peripheral blood specimen for flow cytometry performed at the study institution should be considered. Diagnostic material must have been submitted for cytogenetic and/or molecular testing as clinically appropriate
• Treatment-related mortality (TRM) score \>= 13.1 as calculated with simplified model
• The use of hydroxyurea before enrollment is permitted; hydroxyurea should be discontinued prior to start of study treatment. Patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) \> 100,000/uL or with concern for other complications of high tumor burden or leukostasis (e.g. hypoxia, disseminated intravascular coagulation) can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m\^2) any time prior to enrollment
• Patients may have received low-intensity treatment (e.g. azacitidine/decitabine, lenalidomide, growth factors) for antecedent low-grade myeloid neoplasm (i.e. \< 10% blasts in blood and bone marrow)
• Bilirubin \< 2.0 mg/mL unless elevation is thought to be due to hepatic infiltration by neoplastic cells, Gilbert's syndrome, or hemolysis (assessed within 14 days prior to study day 0)
• Left ventricular ejection fraction (LVEF) \>= 45%, assessed within 12 months prior to registration, e.g. by multigated acquisition scan (MUGA) scan or echocardiography or another appropriate diagnostic modality
• Women of childbearing potential and men must agree to use adequate contraception beginning at the signing of the consent until at least 4 weeks after the last dose of study drug
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment
• Concomitant illness associated with a likely survival of \< 1 year
• Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable. Patients with fever thought to be likely secondary to leukemia are eligible
• Known hypersensitivity to any study drug used in this trial
• Pregnancy or active breast feeding
• Concurrent treatment with any other approved or investigational anti-leukemia agent. Treatment with a FLT3-inhibitor for FLT3-mutated AML is permissible

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute

Interventions

CPX-351; Injections; Cytarabine; Daunorubicin; Liposomes; Cladribine; 2'-chloro-2'-deoxyadenosine; pegylated granulocyte colony-stimulating factor; Mitoxantrone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Membranes, Artificial; Biomedical and Dental Materials; Drug Carriers; Dosage Forms; Pharmaceutical Preparations; Manufactured Materials; Technology, Industry, and Agriculture; Biomimetic Materials; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyadenosines; Deoxyribonucleosides; Ribonucleosides; Anthraquinones; Anthrones; Anthracenes; Quinones

Study Officials

• Roland Walter

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2019
• First Posted: December 12, 2019
• Study Start: March 11, 2020
• Primary Completion: June 6, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)