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

The Washington University

Status and phase: Active, not recruiting; Phase 1

Conditions: Myelodysplastic Syndromes

Treatments: Procedure: Research skin biopsy; Procedure: Research blood draw; Procedure: Research bone marrow aspirate; Drug: CPX-351

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03572764

201807148

Details and patient eligibility

About

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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

CPX-351

Experimental group

Description:

* 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

Treatment:

Drug: CPX-351

Procedure: Research bone marrow aspirate

Procedure: Research blood draw

Procedure: Research skin biopsy