Liposome-Encapsulated Daunorubicin-Cytarabine in Treating Participants with Higher Risk Myelodysplastic Syndrome Who Are Transplant Eligible
This phase I trial studies the side effects of liposome-encapsulated daunorubicin-cytarabine in treating participants with higher risk myelodysplastic syndrome who are transplant eligible. Drugs used in chemotherapy, such as liposome-encapsulated daunorubicin-cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Inclusion Criteria
- Diagnosis of myelodysplastic syndrome (MDS) with an Revised International Prognostic Scoring System (IPSS-R) score of intermediate, high or very high AND >= 5% myeloblasts in the bone marrow
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) * NOTE: If, in the opinion of the treating physician, the bilirubin is elevated secondary to hemolysis or Gilbert’s disease, the patient may be eligible after discussion with the Washington University principal investigator (PI)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x IULN
- Serum creatinine =< 2.0 mg/dL
- Left ventricular cardiac ejection fraction >= 50% by echocardiography or multigated acquisition (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 Institutional Review Board (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 acute myeloid leukemia [AML]-like induction therapy intended for the therapy of MDS). Use of prior growth factor and erythropoietin-stimulating agent (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
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03572764.
PRIMARY OBJECTIVE:
I. To determine the safety and tolerability of a liposome-encapsulated daunorubicin-cytarabine (CPX-351) regimen in a transplant eligible, higher risk myelodysplastic syndrome (MDS) population.
SECONDARY OBJECTIVES:
I. To determine the overall response rate (complete response [CR] + marrow CR + partial response + hematologic improvement), best overall response, remission duration, relapse-free survival, progression-free survival, and overall survival in MDS patients treated with CPX-351.
II. To determine the CR and marrow CR rates in MDS patients treated with CPX-351.
III. To determine the day 30 and day 60 post-induction mortality in MDS patients treated with CPX-351.
IV. To determine the safety and feasibility of CPX-351 consolidation therapy in MDS patients.
V. To determine the proportion of MDS patients treated with CPX-351 proceeding to allogeneic hematopoietic cell transplant.
VI. To determine overall survival, non-relapse mortality and event-free survival at day 100 and 1 year in MDS patients treated with CPX-351 in patients undergoing allogeneic hematopoietic cell transplant (alloHCT).
EXPLORATORY OBJECTIVES:
I. To prospectively collect serial blood and bone marrow specimens to determine biomarkers of response to CPX-351.
II. To determine the measurable residual disease (MRD) after each cycle of CPX-351 therapy using multi-parameter flow cytometry and sequencing (whole genome, exome, patient-specific sequencing, and/or candidate gene assays) and to correlate with traditional International Working Group (IWG) response criteria and outcomes.
OUTLINE: This is a dose-escalation study.
INDUCTION: Participants receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over a minimum of 90 minutes on days 1, 3 and 5 of course 1, and at the discretion of the treating physician on days 1 and 3 of course 2 in the absence of disease progression or unacceptable toxicity.
At the discretion of the treating physician, participants may undergo alloHCT or receive consolidation therapy.
CONSOLIDATION: Beginning 35-75 days after the last induction treatment, participants receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 of course 1. Within 35-56 days after the start of consolidation course 1, participants may undergo alloHCT or receive a second course of consolidation therapy at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at every 3 months for 2 years, then every 6 months for 3 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorMeagan Jacoby
- Primary ID201807148
- Secondary IDsNCI-2018-01608
- ClinicalTrials.gov IDNCT03572764