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

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ClinicalTrials.gov Identifier: NCT03572764
Recruitment Status : Recruiting
First Posted : June 28, 2018
Last Update Posted : December 17, 2018
Sponsor:
Collaborator:
Jazz Pharmaceuticals
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: CPX-351 Procedure: Research skin biopsy Procedure: Research blood draw Procedure: Research bone marrow aspirate Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of CPX-351 (Vyxeos™) for Transplant Eligible, Higher Risk Patients With Myelodysplastic Syndrome
Actual Study Start Date : December 14, 2018
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CPX-351
  • CPX-351 will be given according to the assigned dose level as a 90-minute IV infusion on Days 1, 3, and 5 of the first induction
  • 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
Drug: CPX-351
-CPX-351 will be provided by Jazz Pharmaceuticals
Other Names:
  • Vyxeos™
  • Daunorubicin and cytarabine

Procedure: Research skin biopsy

-And/or buccal swab

  • Pre-treatment
  • Post-induction (no earlier than Day 28 and no later than Day 56 from last induction)

Procedure: Research blood draw
  • Pre-treatment
  • Post-induction (no earlier than Day 28 and no later than Day 56 from last induction)
  • Post-consolidation 1 (if applicable)
  • Post-consolidation 2 (if applicable)
  • Post-transplant Day 30 (if applicable)
  • Post-transplant Day 100 (if applicable)

Procedure: Research bone marrow aspirate
  • Pre-treatment
  • Post-induction (no earlier than Day 28 and no later than Day 56 from last induction)
  • Post-consolidation 1 (if applicable)
  • Post-consolidation 2 (if applicable)
  • Post-transplant Day 30 (if applicable)
  • Post-transplant Day 100 (if applicable)




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Overall response rate in MDS patients treated with CPX-351 [ Time Frame: 56 days after the last dose ]
    • 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

  2. Best overall response in MDS patients treated with CPX-351 [ Time Frame: 56 days after the last dose ]
    -Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS

  3. Remission duration in MDS patients treated with CPX-351 [ Time Frame: Through 5 years ]
    • 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

  4. Relapse-free survival in MDS patients treated with CPX-351 [ Time Frame: Through 5 years ]
    -Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS

  5. Progression-free survival in MDS patients treated with CPX-351 [ Time Frame: Through 5 years ]
    • 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

  6. Overall survival in MDS patients treated with CPX-351 [ Time Frame: Through 5 years ]
    -Defined as the date of first dose of study drug to the date of death from any cause.

  7. Complete remission + marrow complete remission rates in patients treated with CPX-351 [ Time Frame: 56 days after the last dose ]
    -Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS

  8. Post-induction mortality in MDS patients treated with CPX-351 [ Time Frame: Day 30 ]
    -Rate of death

  9. Post-induction mortality in MDS patients treated with CPX-351 [ Time Frame: Day 60 ]
    -Rate of death

  10. 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 ]
  11. Proportion of MDS patients treated with CPX-351 proceeding to allogeneic hematopoietic cell transplant [ Time Frame: Through 56 days after the last dose ]
  12. Overall survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant [ Time Frame: Day 100 ]
    -Defined as the date of first dose of study drug to the date of death from any cause.

  13. Overall survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant [ Time Frame: 1 year ]
    -Defined as the date of first dose of study drug to the date of death from any cause.

  14. Non-relapse mortality in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant [ Time Frame: Day 100 ]
  15. Non-relapse mortality in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant [ Time Frame: 1 year ]
  16. Event-free survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant [ Time Frame: Day 100 ]
    • 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

  17. Event-free survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant [ Time Frame: 1 year ]
    • 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



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  • Direct bilirubin ≤ 1.5 x IULN
  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
  • Serum creatinine ≤ 2.0 mg/dL

    • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03572764


Contacts
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Contact: Meagan Jacoby, M.D., Ph.D. 314-747-7949 mjacoby@wustl.edu

Locations
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United States, Florida
Moffitt Cancer Center Not yet recruiting
Tampa, Florida, United States, 33612
Contact: David Sallman, M.D.    888-663-3488      
Principal Investigator: David Sallman, M.D.         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Meagan Jacoby, M.D., Ph.D.    314-747-7949    mjacoby@wustl.edu   
Principal Investigator: Meagan Jacoby, M.D., Ph.D.         
Sub-Investigator: Geoffrey Uy, M.D.         
Sub-Investigator: Kathryn Trinkaus, Ph.D.         
United States, Washington
Fred Hutchinson Cancer Research Center Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Bart Scott, M.D.    206-667-1990    bscott@fredhutch.org   
Principal Investigator: Bart Scott, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Jazz Pharmaceuticals
Investigators
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Principal Investigator: Meagan Jacoby, M.D., Ph.D. Washington University School of Medicine

Additional Information:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03572764     History of Changes
Other Study ID Numbers: 201807148
First Posted: June 28, 2018    Key Record Dates
Last Update Posted: December 17, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Syndrome
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms