A Trial to Evaluate the Potential Impact of Renal Impairment on the Pharmacokinetics and Safety of CPX-351

A Phase 1 Trial to Evaluate the Potential Impact of Renal Impairment on the Pharmacokinetics and Safety of CPX-351 (Daunorubicin and Cytarabine) Liposome for Injection Treatment in Adult Patients With Hematologic Malignancies

This study evaluates the pharmacokinetics and safety of CPX-351 in patients with moderate or severe renal impairment.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Acute Lymphoblastic Leukemia; Acute Lymphocytic Leukemia; Hematologic Malignancy
• Intervention / Treatment: Drug: CPX-351

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Ontaro
    • Toronto, Ontaro, Canada, M5G 1Z5
      • University Health Network/Princess Margaret Cancer Center
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital - Blood and Bone Marrow Transplant Group of Georgia
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • Valhalla, New York, United States, 10595
      • New York Medical/Westchester
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to understand and voluntarily give informed consent.
2. Male or female patients, age ≥18 years at the time of consent.
3. Diagnosis of hematologic malignancy including, but not limited to, AML, ALL, and MDS. Patients may be newly diagnosed, refractory to initial treatment, or in relapse.
4. Patients with normal renal function, or moderate or severe renal impairment as categorized by creatinine clearance (CrCl)) using the Cockcroft-Gault Formula.
5. Consent of female patients to use a medically acceptable method of contraception for at least 2 months prior to the first dose of CPX-351 and consent of female patients to use a medically acceptable method of contraception throughout the entire study period and for 6 months following the last dose of CPX-351.
6. Male patients must be willing to refrain from sperm donation for 6 months following the last dose of CPX-351and must use adequate contraception throughout the entire study period and for 6 months following the last dose of CPX-351.

Exclusion Criteria:

1. Prior treatment with CPX-351 ≤ to 1 month before the start of CPX-351 in this study.
2. Patients with active (uncontrolled, metastatic) second malignancies are excluded.
3. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent obtaining informed consent.
4. Patients with known hypersensitivity to cytarabine, daunorubicin, or liposomal products.
5. Female patients who are pregnant, nursing, or lactating.
6. Participation in another clinical trial of an investigational drug or medical device within 30 days or 5 half-lives (whichever is longer) prior to enrollment in this study.
7. Any other condition that would cause a risk to patients if they participate in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Normal renal function	Drug: CPX-351; CPX-351 is administered as an intravenous (IV) infusion over approximately 90 minutes.; Other Names: Vyxeos
Experimental: Cohort 2; Moderate renal impairment	Drug: CPX-351; CPX-351 is administered as an intravenous (IV) infusion over approximately 90 minutes.; Other Names: Vyxeos
Experimental: Cohort 3; Severe renal impairment	Drug: CPX-351; CPX-351 is administered as an intravenous (IV) infusion over approximately 90 minutes.; Other Names: Vyxeos

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) of CPX-351	The key PK parameter AUCtau will be assessed	Blood samples will be collected during first induction on Day 1 predose, Day 5 predose, 45 and 90 minutes post infusion start, 2, 3, 4, 6, 8, 24, 48, 96, 168, and 216 hours post Day 5 infusion start.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameter of the individual components of CPX-351, and their respective metabolites	The key PK parameter AUCtau will be assessed	Blood samples will be collected during first induction on Day 1 predose, Day 5 predose, 45 and 90 minutes post infusion start, 2, 3, 4, 6, 8, 24, 48, 96, 168, and 216 hours post Day 5 infusion start.
Incidence of Treatment Emergent Adverse Events (TEAEs)	TEAEs are defined as any AE starting after the initiation of the first infusion.	Up to 31 months.

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2018
• Primary Completion (Actual): May 26, 2021
• Study Completion (Actual): May 26, 2021

Study Registration Dates

• First Submitted: May 14, 2018
• First Submitted That Met QC Criteria: June 1, 2018
• First Posted (Actual): June 14, 2018

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 20, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Leukemia, Lymphoid; Neoplasms; Myelodysplastic Syndromes; Hematologic Neoplasms; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: CPX351-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No