Investigator Initiated Trial of CPX-351 for Untreated Acute Myeloid Leukemia

Phase II Trial of CPX (Cytarabine:Daunorubicin) Liposome Injection in Patients >/=60 Years of Age With AML Previously Untreated By Intensive Chemotherapy

This is an open label study to assess the suitability of CPX-351 as first intensive therapy in elderly (age ≥60 years) patients with AML. Patients may have received prior AML treatment with non-intensive regimens, e.g. hypomethylating agents, low dose Ara C or lenolidomide, but may not have received intensive AML treatment with anthracyclines and/or cytarabine prior to enrollment on this trial. The outcome of elderly patients following intensive treatment with CPX-351 will be measured by clinical endpoints for efficacy and safety and by biological/functional response.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: CPX-351

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability to understand and voluntarily give informed consent
• Age≥60 years at the time of study treatment
• Pathological diagnosis of AML according to WHO criteria (with >20% blasts in the peripheral blood or bone marrow) including:
• De novo AML with normal karyotype or adverse karyotypes (including patients with karyotypic abnormalities characteristic of MDS)
• Secondary AML: transformed from prior MDS or MPN, confirmed by bone marrow documentation of prior antecedent hematologic disorder
• Therapy-related AML: t-AML, requires documented history of prior cytotoxic therapy or ionizing radiotherapy for an unrelated disease
• Performance status >50% KPS, ECOG 0-2
• Laboratory values fulfilling the following:
• Serum creatinine < 2.5 mg/dL
• Serum total bilirubin < 2.5 mg/dL,
• Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULN
• Patients with elevated liver enzymes and serum creatinine values secondary to AML are eligible after discussion with PI
• Cardiac ejection fraction ≥ 50% by echocardiography or MUGA
• Patients with history of second malignancies in remission may be eligible if there is clinical evidence of disease stability off cytotoxic chemotherapy, documented by imaging, tumor marker studies, etc., at screening. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are eligible.

Exclusion Criteria:

• Acute promyelocytic leukemia [t(15;17)]
• Clinical evidence of active CNS leukemia
• Prior intensive chemotherapy for AML with anthracycline/cytarabine-based regimens and/ or prior HSCT. Patients may have been treated with commercially available or investigational hypomethylating agents (e.g. decitabine, azacitidine, SGI-110), lenalidomide, or low-dose cytarabine (not to exceed 20 mg/m2 daily for 14 days for ≤ 6 cycles)
• Prior treatment including HMA, systemic chemotherapy, surgery, or radiation therapy must have been completed at least 7 days before start of study treatment or after discussion with PI. Treatment with investigational agents must have been completed at least 14 days prior to study drug treatment. Hydroxyurea is permitted for control of blood counts before the start of study treatment. Toxicities associated with prior therapies must have recovered to grade 1 or less prior to start of study treatment.
• Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent).
• Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent
• Patients with myocardial impairment of any cause (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging)
• Active or uncontrolled infection. Patients with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥72 hrs.
• Patients with current or recent evidence of invasive fungal infection (blood or tissue culture); patients with recent fungal infection must have a subsequent negative cultures to be eligible
• Known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values)
• Hypersensitivity to cytarabine, daunorubicin or liposomal products
• History of Wilson's disease or other copper-metabolism disorder
• History of prior bone marrow or solid organ transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPX-351 (Cytarabine:Daunorubicin) Injection; Dosing for first induction: CPX-351 • CPX-351 at 100u/m2 will be administered on study days 1, 3 and 5 Dosing for second induction: • CPX-351 at 100 u/m2 will be administered on days 1 and 3 Dosing for consolidation: • CPX-351 at 65 u/m2 will be administered on days 1 and 3	Drug: CPX-351; Cytarabine:Daunorubicin Liposome Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Efficacy	Overall survival is measured from the date of registration to death from any cause. Patients not known to have died will be censored on the date they were last known to be alive. Patients were followed for 2.5 years.	2.5 Years
30-Day Mortality Rate	Mortality rate at Day 30	30 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate (CR, CRp, CRi, and CR+CRp+CRi)	The number of patients who achieve response will be divided by the number of patients in the efficacy population to determine response rate.	30 days post-treatment, up to 3 months post-baseline
Change in Relationship of Cognitive Function to Treatment Response and OS, Event-free Survival and Morphologic Leukemia Free State as Measured by the MOCA	The Montreal Cognitive Assessment (MOCA) is a 30-point test which assesses several cognitive domains. Possible total scores range from 0 to 30. The results can be interpreted as follows: normal cognition: 26-30 points, mild cognitive impairment: 18-25 points, moderate cognitive impairment: 10-17 points, and severe cognitive impairment: under 10 points.	Screening through 30 days post-treatment, up to 3 months post-baseline
Change in Relationship of Cognitive Function to Treatment Response and OS, Event-free Survival and Morphologic Leukemia Free State as Measured by the Blessed Orientation-Memory-Concentration Test	The Blessed Orientation-Memory-Concentration Test is designed to evaluate older patients for early dementia. Possible total scores range from 0 (all items answered correctly) to 28 (all items answered incorrectly).	Screening through 30 days post-treatment, up to 3 months post-baseline
Incidence of Adverse Events	Adverse events included neutropenic fever, transient episodes of pericarditis, febrile neutropenia, streptococcus bacteremia, hypotensive episode, severe diffuse cerebral dysfunction, UTI (klebsiella pneumonia), anorexia with malnutrition, hypophosphatemia, hypokalemia, purple macules, elevated ALT, hypoalbuminemia, hyperbilirubinemia, syncope, joint pain, transaminitis, bacteremia, typhlitis, VRE bacteremia, Osteomyelitis, Decreased LVEF, GI adenovirus, Acute kidney injury, pulmonary edema, neutropenia, bronchospasm, bone pain, urinary incontinence, c. difficile infection, mucositis, and vaginal pain.	Through treatment completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Jazz Pharmaceuticals
• Investigators: Principal Investigator: Ellen K Ritchie, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2017
• Primary Completion (Actual): December 19, 2018
• Study Completion (Actual): May 29, 2020

Study Registration Dates

• First Submitted: September 7, 2017
• First Submitted That Met QC Criteria: November 6, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 1510016710

Drug and device information, study documents

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