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

Myelodysplastic Syndromes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03572764
• Other study ID #: 201807148
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 14, 2018
• Est. completion date: March 25, 2027

Study information

• Verified date: April 2024
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: March 25, 2027
• Est. primary completion date: November 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• CPX-351
-CPX-351 will be provided by Jazz Pharmaceuticals

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)
• 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)
• 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)

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Jazz Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall response rate in MDS patients treated with CPX-351	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	56 days after the last dose
Secondary	Best overall response in MDS patients treated with CPX-351	-Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS	56 days after the last dose
Secondary	Remission duration in MDS patients treated with CPX-351	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	Through 5 years
Secondary	Relapse-free survival in MDS patients treated with CPX-351	-Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS	Through 5 years
Secondary	Progression-free survival in MDS patients treated with CPX-351	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	Through 5 years
Secondary	Overall survival in MDS patients treated with CPX-351	-Defined as the date of first dose of study drug to the date of death from any cause.	Through 5 years
Secondary	Complete remission + marrow complete remission rates in patients treated with CPX-351	-Patients will be assessed for response according to modified International Working Group (IWG) criteria for MDS	56 days after the last dose
Secondary	Post-induction mortality in MDS patients treated with CPX-351	-Rate of death	Day 30
Secondary	Post-induction mortality in MDS patients treated with CPX-351	-Rate of death	Day 60
Secondary	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
Secondary	Proportion of MDS patients treated with CPX-351 proceeding to allogeneic hematopoietic cell transplant		Through 56 days after the last dose
Secondary	Overall survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant	-Defined as the date of first dose of study drug to the date of death from any cause.	Day 100
Secondary	Overall survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant	-Defined as the date of first dose of study drug to the date of death from any cause.	1 year
Secondary	Non-relapse mortality in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant		Day 100
Secondary	Non-relapse mortality in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant		1 year
Secondary	Event-free survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant	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	Day 100
Secondary	Event-free survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant	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	1 year

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine