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

Phase 1

Active, not recruiting

• Conditions: Myelodysplastic Syndromes
• Interventions: Drug: CPX-351; Procedure: Research skin biopsy; Procedure: Research blood draw; Procedure: Research bone marrow aspirate

• Registration Number: NCT03572764
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-06-18
• Study First Submitted QC: 2018-06-18
• Study First Posted: 2018-06-28
• Study Start: 2018-12-14
• Primary Completion: 2021-11-27
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-06
• Last Update Posted: 2024-04-09
• Study Completion: 2027-03-25

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 20

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).

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CPX-351	CPX-351	* CPX-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	Research blood draw	* CPX-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	Research bone marrow aspirate	* CPX-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	Research skin biopsy	* CPX-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

Primary Outcome Measures

Name	Time	Method
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	Through 56 days after the last dose

Secondary Outcome Measures

Name	Time	Method
Overall response rate in MDS patients treated with CPX-351	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
Proportion of MDS patients treated with CPX-351 proceeding to allogeneic hematopoietic cell transplant	Through 56 days after the last dose
Overall survival in MDS patients treated with CPX-351	Through 5 years	-Defined as the date of first dose of study drug to the date of death from any cause.
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	Through 56 days after the last dose
Best overall response in MDS patients treated with CPX-351	56 days after the last dose	-Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS
Post-induction mortality in MDS patients treated with CPX-351	Day 60	-Rate of death
Overall survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant	1 year	-Defined as the date of first dose of study drug to the date of death from any cause.
Remission duration in MDS patients treated with CPX-351	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
Non-relapse mortality in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant	1 year
Event-free survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant	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
Relapse-free survival in MDS patients treated with CPX-351	Through 5 years	-Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS
Progression-free survival in MDS patients treated with CPX-351	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
Complete remission + marrow complete remission rates in patients treated with CPX-351	56 days after the last dose	-Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS

Trial Locations

Locations (3)

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States