CPX-351 in Patients Treated for Higher-risk Myelodysplastic Syndromes Experiencing Hypomethylating Agent Failure.

NCT04109690 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 2000024262
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is of a Liposomal formulation of cytarabine and daunorubicin (CPX-351) in patients treated for higher-risk myelodysplastic syndromes (MDS) experiencing hypomethylating agent failure.

Conditions

MDS

Keywords

MDS

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  The Phase II primary objective is to determine the overall response rate (CR/CRi) of CPX-351 in MDS patients experiencing hypomethylation (HMA) failure.

  Up to 24 months

Study Arms (1)

CPX-351

EXPERIMENTAL

Phase I will evaluate the safety and tolerability of CPX-351 (44mg/m2 of daunorubicin and 100mg/m2 of cytarabine) administered on 2 days (day 1 and day 5) to determine the Phase II dose. Phase II will evaluate the efficacy of the RP2D.

Drug: CPX-351

Interventions

CPX-351 DRUG

Patients in both Phase I and II can receive a maximum of two induction and six consolidation cycles on an inpatient or outpatient basis per local hospital standard of care.

CPX-351

Eligibility Criteria

• Age: 18 Years - 78 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a diagnosis of MDS o (according to World Health Organization 2016 classification) made prior to administration off HMA
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
• Patient must have recovered from toxicities of any prior treatment regimen (no CTCAE grading over 1 for non-hematological toxicities and a return to baseline for hematological values)
• Patient is considered eligible for chemotherapy (at discretion of local investigator)
• Patient must have been treated with a hypomethylating agent (+/- other agents) and
• be treated for at least 4 cycles (16 weeks) and have a stable marrow disease (no response) or
• progressed without prior response based on MDS International Working Group (IWG) 2006 response criteria or
• relapsed after an initial response based on MDS IWG 2006 response criteria.
• Adequate liver and renal function:
• Estimated creatinine clearance above 40 ml/min
• Total bilirubin ≤ 1.5 x the Upper Limit of Normal (ULN) or ≤ 3.0 x the ULN unless considered due to Gilbert's syndrome,
• Alanine aminotransferase (ALT) (SGPT), and aspartate aminotransferase (AST) (SGOT) ≤ 2.5 x the ULN. For patients with hepatic leukemic involvement Alanine aminotransferase (ALT) (SGPT), and aspartate aminotransferase (AST) (SGOT) ≤ 5.0 x the ULN t
• Able to understand and sign the written informed consent
• Serum or urine pregnancy test (for female patients of childbearing potential) with a minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin (HCG) negative at screening.
• Males and female patients both of childbearing potential and at risk for pregnancy must agree to use two highly effective method(s) of contraception throughout the study and for 180 days after the last dose of CPX-351 whichever occurs later.

You may not qualify if:

• Any prior induction chemotherapy (defined as treatment with standard or high dose cytarabine in combination with an anthracycline and/or other agents)
• Promyelocytic acute leukemia and core binding factor acute leukemia.
• Active Central nervous system (CNS) disease
• Any severe chronic disease potentially interfering with the protocol including HIV infection, active or chronic hepatitis B or C. Testing will be completed during screening period.
• Any significant social condition that could limit the understanding of the study or the compliance to the protocol including but not limited to severe or uncontrolled psychiatric illness.
• Any sign of active uncontrolled disease including but not restricted to cardiac disease, infections and platelet refractoriness.
• Any other malignancy with active treatment within the past 1 year other than basal cell skin cancer or carcinoma in situ of the cervix.
• New York Heart Association (NYHA) grade 3 or 4 cardiac failure, or left ventricular ejection fraction (LVEF) below 50%
• Patients who have received a cumulative dose of anthracyclines superior to a total of 300mg/m2 of daunorubicin in the absence of prior mediastinal radiation or 150mg/m2 if the patient had a prior mediastinal radiation
• Oxygen dependency as defined by a chronic need of oxygen at least 2l/min for at least 6h a day.
• Women who are pregnant, planning to become pregnant, or who are currently breastfeeding
• Persistence of any clinically relevant (CTCAE grade 2 or above) toxicities from previous therapy
• Any other condition that, according to the investigator, may forbid the administration of CPX-351
• Hypersensitivity to cytarabine, daunorubicin or liposomal products
• History of Wilson's disease or another copper-metabolism disorder

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale University; Smilow Cancer Center

New Haven, Connecticut, 06519, United States

Location

MeSH Terms

Interventions

CPX-351

Study Officials

• Thomas Prebet, MD, PHD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: September 30, 2019
• Study Start: December 30, 2019
• Primary Completion: July 27, 2021
• Study Completion: July 27, 2021
• Last Updated: January 24, 2022

Record last verified: 2022-01

Locations

US (1)