CPX-351 in Treating Patients With Relapsed or Refractory High Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

NCT03896269 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2018-0911NCI-2019-01558
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies best dose and side effects of liposome-encapsulated daunorubicin-cytarabine (CPX-351) and how well it works in treating patients with high risk myelodysplastic syndrome or chronic myelomonocytic leukemia that has come back or has not responded to treatment. Drugs used in chemotherapy, such as liposome-encapsulated daunorubicin-cytarabine, 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.

Conditions

Blasts More Than 5 Percent of Bone Marrow Nucleated Cells; High Risk Chronic Myelomonocytic Leukemia; Recurrent Chronic Myelomonocytic Leukemia; Recurrent High Risk Myelodysplastic Syndrome; Refractory Chronic Myelomonocytic Leukemia; Refractory High Risk Myelodysplastic Syndrome; Blasts 10-19 Percent of Bone Marrow Nucleated Cells

Outcome Measures

Primary Outcomes (4)

• Incidence of adverse events (dose-escalation stage)

  Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median, and range. Toxicity type, severity, and attribution will be summarized for each patient using frequency tables.

  Up to 30 days

• Maximum-tolerated dose (MTD) of liposome-encapsulated daunorubicin-cytarabine (dose-escalation stage)

  Defined as the highest dose level in which a dose-limiting toxicity (DLT) occurs within at most 1 out of 6 patients treated. DLTs are defined as any related non-hematological Common Terminology Criteria for Adverse Events grade \>= 3 adverse events that prevent further administration of the agent at that same dose level.

  Up to 28 days

• Incidence of adverse events (dose-expansion stage)

  Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median, and range. Toxicity type, severity, and attribution will be summarized for each patient using frequency tables.

  Up to 30 days

• Objective response rate (ORR) (dose-expansion stage)

  Defined as complete response (CR), partial response, CR with incomplete bone marrow recovery, marrow CR or hematological improvement. Will be estimated along with 95% confidence intervals treated at the MTD (i.e., including those treated at the MTD during dose escalation and dose expansion phases). The association between ORR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.

  Up to 1.5 years

Secondary Outcomes (5)

• Overall response rate

  Up to 1.5 years

• Overall survival

  Up to 1.5 years

• Duration of response

  Up to 1.5 years

• Relapse-free survival

  Up to 1.5 years

• Incidence of adverse events

  Up to 1.5 years

Study Arms (1)

Treatment (liposome-encapsulated daunorubicin-cytarabine)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. After 2-5 weeks, patients who do not achieve a CR/CRi/CRp, have acceptable or no toxicity, and have stable disease and no disease progression may receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients who achieve at least a HI response, receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After 5-8 weeks, patients who do not show clinically significant disease progression or unacceptable toxicity may receive liposome-encapsulated daunorubicin-cytarabine for up to 12 additional cycles.

Drug: Liposome-encapsulated Daunorubicin-Cytarabine

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

Treatment (liposome-encapsulated daunorubicin-cytarabine)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of MDS or chronic myelomonocytic leukemia (CMML) according to World Health Organization (WHO)
• Patients are either not eligible for or choose not to proceed with a stem cell transplant at the time of enrollment
• MDS and CMML classified by International Prognostic Scoring System (IPSS) as intermediate-2/high risk with excess blasts \> 5%, or with 10-19% bone marrow blasts
• No response following at least 4 cycles of therapy or relapse after initial CR, partial response (PR), or HI or progression after any number of cycles of either azacitidine, decitabine, guadecitabine or ASTX727 (oral decitabine) as single agents or in combination with other investigational agents
• Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study
• Total bilirubin \< 3 mg/dL (will allow less than 5 x upper limit of normal \[ULN\] if Gilbert's at investigator's discretion)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x ULN
• Serum creatinine clearance \> 30 mL/min and no end/stage renal disease
• Hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, granulocyte-colony stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor \[GM-CSF\], procrit, aranesp, thrombopoietins) is allowed at any time prior to or during study if considered to be in the best interest of the patient

You may not qualify if:

• New York Heart Association (NYHA) class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) \< 50 by echocardiogram or multigated acquisition (MUGA) scan
• History of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias
• Uncontrolled infection not adequately responding to appropriate antibiotics
• Female patients who are pregnant or lactating
• Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives \[birth control pills\], contraceptive injections, intrauterine devices \[IUD\], double-barrier method \[spermicidal jelly or foam with condoms or diaphragm\], contraceptive patch, or surgical sterilization) throughout the study
• Female patients with reproductive potential who have a positive urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening
• Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy (within 14 days of initiating study treatment)
• Prior cumulative anthracycline exposure of \> 550 mg/m\^2 daunorubicin or equivalent, or \> 400 mg/m\^2 in patients who received radiation therapy to the mediastinum

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• Montalban-Bravo G, Jabbour E, Borthakur G, Kadia T, Ravandi F, Chien K, Pemmaraju N, Hammond D, Dong XQ, Huang X, Schneider H, John R, Kanagal-Shamana R, Loghavi S, Kantarjian H, Garcia-Manero G. Phase 1/2 study of CPX-351 for patients with Int-2 or high risk International Prognostic Scoring System myelodysplastic syndromes and chronic myelomonocytic leukaemia after failure to hypomethylating agents. Br J Haematol. 2024 Mar;204(3):898-909. doi: 10.1111/bjh.19193. Epub 2023 Nov 10.

  PMID: 37946611 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic

Interventions

CPX-351; Injections; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

Study Officials

• Guillermo M Bravo

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guillermo M Bravo

CONTACT

713-794-3604; gmontalban1@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: March 29, 2019
• Study Start: May 14, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

US (1)