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NCT Number: NCT04668885

CPX-351 as a Novel Approach for the Treatment of Older Patients With AML and MDS

The purpose of this study is to evaluate how effective lower doses of CPX-351 are in older participants with relapsed/refractory acute myeloid leukemia (AML) who are not eligible to receive intensive chemotherapy and in participants with myelodysplastic syndromes (MDS) after Hypomethylating Agents (HMA) failure.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Refractory Acute Myeloid Leukemia Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Myelomonocytic, Acute Myelodysplastic Syndromes Neoplasms Neoplasms by Histologic Type Relapsed Acute Myelomonocytic Leukemia

Age range

60 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

About this study

Currently, elderly patients with AML and high risk MDS, who are ineligible to receive induction chemotherapy and fail HMA +/- combination, have very poor outcomes and there is no FDA-approved therapy outside of some targeted therapies which can only be applied to a small patient population. CPX-351 is an investigational (experimental) drug that works by combining two anti-cancer drugs cytarabine and daunorubicin. CPX-351 is experimental because it is only FDA approved for the treatment of adults with two types of AML: newly diagnosed therapy-related AML or AML with myelodysplasia-related changes.

This is an open label clinical trial of lower doses of CPX-351 in relapsed/primary refractory older AML and MDS patients ineligible to receive intensive chemotherapy. The first arm is for particpants with primary refractory/relapsed AML and the second arm is for higher risk MDS participants after HMA failure.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Primary refractory or relapsed AML (defined by 2016 World Health Organization [WHO] criteria) patients who are not suitable for or not willing to receive intensive chemotherapy as evaluated by the treating physician. Primary refractory disease is defined as:
  • Failure to achieve a CR, CRi, or mLFS (defined as <5% Bone Marrow (BM) blasts) after receiving 1 or 2 cycles of remission induction chemotherapy.
  • Failure to achieve a CR, CRi, or MLFS (defined as <5% BM blasts) after receiving 4 cycles of non-intensive chemotherapy or whose disease progressed at any time point during the treatment.
  • Participants with MDS (according to 2016 WHO criteria) who did not respond to treatment with azacitidine, decitabine, or combination of HMA with another drug or lost their response to initial therapy with HMA.
  • Eastern Cooperative Oncology Group (ECOG) performance status <=2
  • Adequate hepatic (serum total bilirubin < 1.5 x ULN, Serum glutamic pyruvic transaminase (SGPT) and/or serum glutamate oxaloacetate transaminase (SGOT) <2.5 x ULN) and renal function (creatinine < 1.5mg/dL).
  • Participants must be willing and able to review, understand, and provide written consent before starting therapy.

Exclusion criteria

  • Active signs or symptoms of central nervous system (CNS) involvement by malignancy (lumbar puncture [LP] not required).
  • Prior 7+3 remission induction chemotherapy for MDS or AML
  • More than 2 lines of prior non-intensive therapy.
  • New York Heart Association (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia on rhythm control strategy or on pacemaker, uncontrolled hypertension (blood pressure > 160 systolic and > 110 diastolic not responsive to antihypertensive medication)
  • Acute myocardial infarction in the previous 12 weeks (from the start of treatment).
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent.
  • Any active malignancy (unrelated, non-hematological malignancy) diagnosed within the past 6 months of starting the study drug (other than curatively treated carcinoma-in-situ of the cervix or non-melanoma skin cancer).
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to CPX-351.
  • Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Known history of HIV or active hepatitis B or C.
  • No major surgery within 2 weeks prior to study enrollment.
  • Pregnant or breast feeding
  • Male and female participants who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence) to avoid pregnancy while receiving study treatment and for 30 days after last dose of study treatment. Non-childbearing is defined as > 1 year postmenopausal or surgically sterilized.
  • Acute promyelocytic leukemia (APL)

Treatment and study plan

CPX-351

Drug

Induction phase: CPX-351 15 mg/m^2 on days 1 and 3 of each 28-day cycle for up to a total of 6 cycles in the absence of unacceptable toxicity

Maintenance phase: CPX-351 7.5 mg/m^2 on days 1 and 3 for two cycles alternating with 15 mg/m^2 for one cycle. Participants may receive up to 12 cycles of maintenance phase in the absence of unacceptable toxicity.

Primary outcomes

  1. Overall response rate (ORR) per 2003 International Working Group (IWG) criteria

    Time frame: At 6 months

    ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  2. Overall response rate (ORR) per 2003 IWG criteria

    Time frame: At 1 year

    ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  3. Overall response rate (ORR) per 2003 IWG criteria

    Time frame: At 1.5 years

    ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  4. Overall response rate (ORR) per 2003 IWG criteria

    Time frame: At 2 years

    ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  5. Overall response rate (ORR) per 2003 IWG criteria

    Time frame: At 2.5 years

    ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  6. Overall response rate (ORR) per 2003 IWG criteria

    Time frame: At 3 years

    ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  7. Overall response rate (ORR) per 2003 IWG criteria

    Time frame: At 3.5 years

    ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  8. Overall response rate (ORR) per 2003 IWG criteria

    Time frame: At 4 years

    ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  9. Overall response rate (ORR) per 2003 IWG criteria

    Time frame: At 4.5 years

    ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  10. Overall response rate (ORR) per 2003 IWG criteria

    Time frame: At 5 years

    ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

Secondary outcomes

  1. Time to response (TTR)

    Time frame: At 6 months

    TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables.

  2. Time to response (TTR)

    Time frame: At 1 year

    TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables.

  3. Time to response (TTR)

    Time frame: At 1.5 years

    TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables.

  4. Time to response (TTR)

    Time frame: At 2 years

    TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables.

  5. Time to response (TTR)

    Time frame: At 2.5 years

    TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables.

  6. Time to response (TTR)

    Time frame: At 3 years

    TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables.

  7. Time to response (TTR)

    Time frame: At 3.5 years

    TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables.

  8. Time to response (TTR)

    Time frame: At 4 years

    TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables.

  9. Time to response (TTR)

    Time frame: At 4.5 years

    TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables.

  10. Time to response (TTR)

    Time frame: At 5 years

    TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables.

  11. Duration of response (DOR)

    Time frame: At 6 months

    DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables.

  12. Duration of response (DOR)

    Time frame: At 1 year

    DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables.

  13. Duration of response (DOR)

    Time frame: At 1.5 years

    DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables.

  14. Duration of response (DOR)

    Time frame: At 2 years

    DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables.

  15. Duration of response (DOR)

    Time frame: At 2.5 years

    DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables.

  16. Duration of response (DOR)

    Time frame: At 3 years

    DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables.

  17. Duration of response (DOR)

    Time frame: At 3.5 years

    DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables.

  18. Duration of response (DOR)

    Time frame: At 4 years

    DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables.

  19. Duration of response (DOR)

    Time frame: At 4.5 years

    DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables.

  20. Duration of response (DOR)

    Time frame: At 5 years

    DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables.

  21. Event-free survival (EFS)

    Time frame: At 6 months

    EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables

  22. Event-free survival (EFS)

    Time frame: At 1 year

    EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables

  23. Event-free survival (EFS)

    Time frame: At 1.5 years

    EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables

  24. Event-free survival (EFS)

    Time frame: At 2 years

    EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables

  25. Event-free survival (EFS)

    Time frame: At 2.5 years

    EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables

  26. Event-free survival (EFS)

    Time frame: At 3 years

    EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables

  27. Event-free survival (EFS)

    Time frame: At 3.5 years

    EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables

  28. Event-free survival (EFS)

    Time frame: At 4 years

    EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables

  29. Event-free survival (EFS)

    Time frame: At 4.5 years

    EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables

  30. Event-free survival (EFS)

    Time frame: At 5 years

    EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables

  31. Overall Survival (OS)

    Time frame: At 6 months

    OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method

  32. Overall Survival (OS)

    Time frame: At 1 year

    OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method

  33. Overall Survival (OS)

    Time frame: At 1.5 years

    OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method

  34. Overall Survival (OS)

    Time frame: At 2 years

    OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method

  35. Overall Survival (OS)

    Time frame: At 2.5 years

    OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method

  36. Overall Survival (OS)

    Time frame: At 3 years

    OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method

  37. Overall Survival (OS)

    Time frame: At 3.5 years

    OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method

  38. Overall Survival (OS)

    Time frame: At 4 years

    OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method

  39. Overall Survival (OS)

    Time frame: At 4.5 years

    OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method

  40. Overall Survival (OS)

    Time frame: At 5 years

    OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method

Sponsors and collaborators

Lead sponsor

Case Comprehensive Cancer Center

Other

Registry information

Official study title

Lower Doses of CPX-351 as a Novel Approach for the Treatment of Older Patients With Relapsed or Refractory Acute Myeloid Leukemia and Myelodysplastic Syndromes

Important dates

Study start
2021
Primary completion
2026
Study completion
2027
First posted
Dec 16, 2020
Registry last updated
Jun 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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