Clinical Trials /

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

NCT03896269

Description:

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.

Related Conditions:
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CPX-351 in Treating Patients With Relapsed or Refractory High Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
  • Official Title: Phase 1 Dose Escalation Study of CPX-351 for Patients With Int-2 or High Risk IPSS Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia After Failure to Hypomethylating Agents

Clinical Trial IDs

  • ORG STUDY ID: 2018-0911
  • SECONDARY ID: NCI-2019-01558
  • SECONDARY ID: 2018-0911
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03896269

Conditions

  • Blasts 10-19 Percent of Bone Marrow Nucleated Cells
  • 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

Interventions

DrugSynonymsArms
Liposome-encapsulated Daunorubicin-CytarabineCPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, VyxeosTreatment (liposome-encapsulated daunorubicin-cytarabine)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To characterize the safety and tolerability of CPX-351 in patients with intermediate-2 or
      high-risk myelodysplastic syndrome (MDS). (Dose Escalation Stage) II. To determine the
      maximum tolerated dose (MTD) of intravenous CPX-351 in patients with intermediate-2 or
      high-risk MDS. (Dose Escalation Stage) III. To further characterize the safety and
      tolerability of CPX-351 in patients with intermediate-2 and high-risk MDS. (Dose-Expansion
      Stage) IV. To evaluate preliminary efficacy of CPX-351 in patients with intermediate-2 or
      high-risk MDS. (Dose-Expansion Stage)

      SECONDARY OBJECTIVES:

      I. To assess overall response (OR) rate. II. To assess overall survival. III. To assess
      duration of response. IV. To assess relapse-free survival. V. To assess safety profile.

      OUTLINE: This is a dose-escalation study.

      INDUCTION THERAPY: Patients receive liposome-encapsulated daunorubicin-cytarabine
      intravenously (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 complete response
      (CR)/CR with incomplete bone marrow recovery (CRi)/CR with incomplete platelet recovery
      (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 hematological improvement (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.

      After completion of study treatment, patients are followed up at 30 days and then every 6
      months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (liposome-encapsulated daunorubicin-cytarabine)ExperimentalINDUCTION 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.
  • Liposome-encapsulated Daunorubicin-Cytarabine

Eligibility Criteria

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (dose-escalation stage)
Time Frame:Up to 30 days
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 1.5 years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Up to 1.5 years
Safety Issue:
Description:The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Measure:Duration of response
Time Frame:Up to 1.5 years
Safety Issue:
Description:Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
Measure:Relapse-free survival
Time Frame:Up to 1.5 years
Safety Issue:
Description:The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Measure:Incidence of adverse events
Time Frame:Up to 1.5 years
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

October 3, 2019