Clinical trial NCT03572764: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Myelodysplastic Syndromes
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Jazz Pharmaceuticals
First posted: 2018-06-28
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
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
timeFrame: Through 56 days after the last dose
Secondary outcomes:
measure: Overall response rate in MDS patients treated with CPX-351
timeFrame: 56 days after the last dose
measure: Best overall response in MDS patients treated with CPX-351
timeFrame: 56 days after the last dose
measure: Remission duration in MDS patients treated with CPX-351
timeFrame: Through 5 years
measure: Relapse-free survival in MDS patients treated with CPX-351
timeFrame: Through 5 years
measure: Progression-free survival in MDS patients treated with CPX-351
timeFrame: Through 5 years
measure: Overall survival in MDS patients treated with CPX-351
timeFrame: Through 5 years
measure: Complete remission + marrow complete remission rates in patients treated with CPX-351
timeFrame: 56 days after the last dose
measure: Post-induction mortality in MDS patients treated with CPX-351
timeFrame: Day 30
measure: Post-induction mortality in MDS patients treated with CPX-351
timeFrame: Day 60
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
timeFrame: Through 56 days after the last dose
measure: Proportion of MDS patients treated with CPX-351 proceeding to allogeneic hematopoietic cell transplant
timeFrame: Through 56 days after the last dose
measure: Overall survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
timeFrame: Day 100
measure: Overall survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
timeFrame: 1 year
measure: Non-relapse mortality in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
timeFrame: Day 100
measure: Non-relapse mortality in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
timeFrame: 1 year
measure: Event-free survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
timeFrame: Day 100
measure: Event-free survival in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant
timeFrame: 1 year
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Washington University School of Medicine
name: Meagan Jacoby, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: