Clinical Trials /

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

NCT04668885

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CPX-351 as a Novel Approach for the Treatment of Older Patients With AML and MDS
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: CASE1920
  • NCT ID: NCT04668885

Conditions

  • Refractory Acute Myeloid Leukemia
  • Relapsed Acute Myelomonocytic Leukemia
  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
CPX-351MDS after HMA failure

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Primary refractory/relapsed AMLExperimentalLower dose CPX-351 in participants with primary refractory/relapsed AML. Participants will receive an induction and maintenance phase of CPX-351
  • CPX-351
MDS after HMA failureExperimentalLower dose CPX-351 in participants with MDS after HMA failure. Participants will receive an induction and maintenance phase of CPX-351
  • CPX-351

Eligibility Criteria

        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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR) per 2003 International Working Group (IWG) criteria
Time Frame:At 6 months
Safety Issue:
Description: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 Outcome Measures

Measure:Time to response (TTR)
Time Frame:At 6 months
Safety Issue:
Description: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.
Measure:Time to response (TTR)
Time Frame:At 1 year
Safety Issue:
Description: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.
Measure:Time to response (TTR)
Time Frame:At 1.5 years
Safety Issue:
Description: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.
Measure:Time to response (TTR)
Time Frame:At 2 years
Safety Issue:
Description: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.
Measure:Time to response (TTR)
Time Frame:At 2.5 years
Safety Issue:
Description: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.
Measure:Time to response (TTR)
Time Frame:At 3 years
Safety Issue:
Description: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.
Measure:Time to response (TTR)
Time Frame:At 3.5 years
Safety Issue:
Description: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.
Measure:Time to response (TTR)
Time Frame:At 4 years
Safety Issue:
Description: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.
Measure:Time to response (TTR)
Time Frame:At 4.5 years
Safety Issue:
Description: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.
Measure:Time to response (TTR)
Time Frame:At 5 years
Safety Issue:
Description: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.
Measure:Duration of response (DOR)
Time Frame:At 6 months
Safety Issue:
Description: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.
Measure:Duration of response (DOR)
Time Frame:At 1 year
Safety Issue:
Description: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.
Measure:Duration of response (DOR)
Time Frame:At 1.5 years
Safety Issue:
Description: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.
Measure:Duration of response (DOR)
Time Frame:At 2 years
Safety Issue:
Description: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.
Measure:Duration of response (DOR)
Time Frame:At 2.5 years
Safety Issue:
Description: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.
Measure:Duration of response (DOR)
Time Frame:At 3 years
Safety Issue:
Description: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.
Measure:Duration of response (DOR)
Time Frame:At 3.5 years
Safety Issue:
Description: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.
Measure:Duration of response (DOR)
Time Frame:At 4 years
Safety Issue:
Description: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.
Measure:Duration of response (DOR)
Time Frame:At 4.5 years
Safety Issue:
Description: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.
Measure:Duration of response (DOR)
Time Frame:At 5 years
Safety Issue:
Description: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.
Measure:Event-free survival (EFS)
Time Frame:At 6 months
Safety Issue:
Description: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
Measure:Event-free survival (EFS)
Time Frame:At 1 year
Safety Issue:
Description: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
Measure:Event-free survival (EFS)
Time Frame:At 1.5 years
Safety Issue:
Description: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
Measure:Event-free survival (EFS)
Time Frame:At 2 years
Safety Issue:
Description: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
Measure:Event-free survival (EFS)
Time Frame:At 2.5 years
Safety Issue:
Description: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
Measure:Event-free survival (EFS)
Time Frame:At 3 years
Safety Issue:
Description: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
Measure:Event-free survival (EFS)
Time Frame:At 3.5 years
Safety Issue:
Description: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
Measure:Event-free survival (EFS)
Time Frame:At 4 years
Safety Issue:
Description: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
Measure:Event-free survival (EFS)
Time Frame:At 4.5 years
Safety Issue:
Description: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
Measure:Event-free survival (EFS)
Time Frame:At 5 years
Safety Issue:
Description: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
Measure:Overall Survival (OS)
Time Frame:At 6 months
Safety Issue:
Description:OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method
Measure:Overall Survival (OS)
Time Frame:At 1 year
Safety Issue:
Description:OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method
Measure:Overall Survival (OS)
Time Frame:At 1.5 years
Safety Issue:
Description:OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method
Measure:Overall Survival (OS)
Time Frame:At 2 years
Safety Issue:
Description:OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method
Measure:Overall Survival (OS)
Time Frame:At 2.5 years
Safety Issue:
Description:OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method
Measure:Overall Survival (OS)
Time Frame:At 3 years
Safety Issue:
Description:OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method
Measure:Overall Survival (OS)
Time Frame:At 3.5 years
Safety Issue:
Description:OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method
Measure:Overall Survival (OS)
Time Frame:At 4 years
Safety Issue:
Description:OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method
Measure:Overall Survival (OS)
Time Frame:At 4.5 years
Safety Issue:
Description:OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method
Measure:Overall Survival (OS)
Time Frame:At 5 years
Safety Issue:
Description:OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Last Updated

December 16, 2020