Clinical Trials /

CPX-351 (Vyxeos™) for Transplant Eligible, Higher Risk Patients With Myelodysplastic Syndrome

NCT03572764

Description:

This is a pilot and feasibility study of transplant eligible, higher risk myelodysplastic syndrome (MDS) patients to determine the safety and tolerability of a lower -dose and higher-dose CPX-351 regimen, with secondary objectives including complete remission (CR) rates and proportion of patients proceeding to transplant.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CPX-351 (Vyxeos™) for Transplant Eligible, Higher Risk Patients With Myelodysplastic Syndrome
  • Official Title: A Pilot Study of CPX-351 (Vyxeos™) for Transplant Eligible, Higher Risk Patients With Myelodysplastic Syndrome

Clinical Trial IDs

  • ORG STUDY ID: 201807148
  • NCT ID: NCT03572764

Conditions

  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
CPX-351Vyxeos™, Daunorubicin and cytarabineCPX-351

Purpose

This is a pilot and feasibility study of transplant eligible, higher risk myelodysplastic syndrome (MDS) patients to determine the safety and tolerability of a lower -dose and higher-dose CPX-351 regimen, with secondary objectives including complete remission (CR) rates and proportion of patients proceeding to transplant.

Trial Arms

NameTypeDescriptionInterventions
CPX-351ExperimentalCPX-351 will be given according to the assigned dose level over a minimum of a 90-minutes via IV infusion on Days 1, 3, and 5 of the first induction If the treating physician elects to perform a day 14 bone marrow biopsy then, a second induction may be considered for patients in the absence of a chemoablated, hypocellular marrow on the Day 14 bone marrow assessment, if the patient has failed to achieve a marrow CR, and it is deemed safe to administer by the treating physician. The second induction uses a modified schedule in which CPX-351 will be given according to the assigned dose level on Days 1 and 3 In the absence of disease progression or unacceptable toxicity, the patient may continue to consolidation at the discretion of the treating physician or the patient may proceed to alloHCT after induction at the discretion of the treating physician
  • CPX-351

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of myelodysplastic syndrome (MDS) with an IPSS-R score of Intermediate, High
             or Very High (see Appendix A) AND ≥ 5% myeloblasts in the bone marrow.

          -  Age 18-70 years.

          -  ECOG performance status ≤ 2 (see Appendix B)

        Adequate renal and hepatic function as defined below:

        *Total bilirubin ≤ 2.0 x IULN*

          -  AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

          -  Serum creatinine ≤ 2.0 mg/dL

          -  Note: If, in the opinition of the treatment physician, the bilirubin is elevated
             secondary to hemolysis or Gilbert's disease, the patient may be eligible after
             discussion with the Washington University PI.

               -  Left ventricular cardiac ejection fraction ≥ 50% by echocardiography or MUGA.

               -  Deemed by the treating physician to be a suitable candidate for cytotoxic
                  induction therapy and an alloHCT candidate at the time of enrollment.

               -  Women of childbearing potential and men must agree to use adequate contraception
                  (hormonal or barrier method of birth control, abstinence) prior to study entry
                  and continuing until 30 days after the last study treatment.

               -  Ability to understand and willingness to sign an IRB approved written informed
                  consent document (or that of legally authorized representative, if applicable).

        Exclusion Criteria:

          -  Prior treatment for MDS with disease-modifying therapy (conventional or
             investigational) (i.e. hypomethylator therapy, lenalidomide, or prior AML-like
             induction therapy intended for the therapy of MDS). Use of prior growth factor and ESA
             support is permitted.

          -  Currently receiving any other investigational agents.

          -  A history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to CPX-351 or other agents used in the study.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
             arrhythmia.

          -  History of Wilson's disease or other copper-metabolism disorder.

          -  Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
             pregnancy test within 14 days of study entry.

          -  Known active viral infection with human immunodeficiency virus (HIV), hepatitis B
             virus (HBV), or hepatitis C virus (HCV). Patients who are seropositive because of
             hepatitis B virus vaccine are eligible. Patients who are seropositive for HCV but have
             a negative viral load are also eligible provided that the patient has completed a
             course of therapy for HCV.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of a CPX-351 regimen in a transplant eligible, higher risk MDS population as measured by the proportion of participants who experience an adverse event by patient, type of event, and grade of event
Time Frame:Through 56 days after the last dose
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rate in MDS patients treated with CPX-351
Time Frame:56 days after the last dose
Safety Issue:
Description:Overall response rate = complete remission + marrow complete remission + partial response + hematologic improvement Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS
Measure:Best overall response in MDS patients treated with CPX-351
Time Frame:56 days after the last dose
Safety Issue:
Description:-Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS
Measure:Remission duration in MDS patients treated with CPX-351
Time Frame:Through 5 years
Safety Issue:
Description:Defined as the interval from the date complete remission is documented to the date of recurrence. This is determined only for patients achieving a complete remission. Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS
Measure:Relapse-free survival in MDS patients treated with CPX-351
Time Frame:Through 5 years
Safety Issue:
Description:-Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS
Measure:Progression-free survival in MDS patients treated with CPX-351
Time Frame:Through 5 years
Safety Issue:
Description:Defined as the interval from the date of first dose of study drug to disease progression or death from MDS. Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS
Measure:Overall survival in MDS patients treated with CPX-351
Time Frame:Through 5 years
Safety Issue:
Description:-Defined as the date of first dose of study drug to the date of death from any cause.
Measure:Complete remission + marrow complete remission rates in patients treated with CPX-351
Time Frame:56 days after the last dose
Safety Issue:
Description:-Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS
Measure:Post-induction mortality in MDS patients treated with CPX-351
Time Frame:Day 30
Safety Issue:
Description:-Rate of death
Measure:Post-induction mortality in MDS patients treated with CPX-351
Time Frame:Day 60
Safety Issue:
Description:-Rate of death
Measure:Safety and feasibility of CPX-351 consolidation therapy in MDS patients as measured by the proportion of patients who experience an adverse event by patient, type of event, and grade of event
Time Frame:Through 56 days after the last dose
Safety Issue:
Description:
Measure:Proportion of MDS patients treated with CPX-351 proceeding to allogeneic hematopoietic cell transplant
Time Frame:Through 56 days after the last dose
Safety Issue:
Description:
Measure:Overall survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
Time Frame:Day 100
Safety Issue:
Description:-Defined as the date of first dose of study drug to the date of death from any cause.
Measure:Overall survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
Time Frame:1 year
Safety Issue:
Description:-Defined as the date of first dose of study drug to the date of death from any cause.
Measure:Non-relapse mortality in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
Time Frame:Day 100
Safety Issue:
Description:
Measure:Non-relapse mortality in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
Time Frame:1 year
Safety Issue:
Description:
Measure:Event-free survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
Time Frame:Day 100
Safety Issue:
Description:Defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, or death due to any cause. Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS
Measure:Event-free survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
Time Frame:1 year
Safety Issue:
Description:Defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, or death due to any cause. Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

May 8, 2020