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

NCT03335267 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1510016710
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Complete Response Rate (CR, CRp, CRi, and CR+CRp+CRi)

  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

  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

  Screening through 30 days post-treatment, up to 3 months post-baseline

• Incidence of Adverse Events

  Through treatment completion, an average of 1 year

Study Arms (1)

CPX-351 (Cytarabine:Daunorubicin) Injection

EXPERIMENTAL

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

Interventions

CPX-351 DRUG

Cytarabine:Daunorubicin Liposome Injection

CPX-351 (Cytarabine:Daunorubicin) Injection

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

CPX-351

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

We intended to collect and compare baseline and end of induction data to assess the relationship of cognitive function to treatment response and overall survival, event-free survival, and morphologic leukemia free state. Subjects on treatment were usually too unwell to complete the questionnaires, which resulted in significant missing data. We were unable to determine if the relationship was statistically significant.

Results Point of Contact

• Title: Dr. Ellen K. Ritchie
• Organization: Weill Cornell Medical College

ritchie@med.cornell.edu

646-962-2700

Study Officials

• Ellen K Ritchie, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: November 7, 2017
• Study Start: October 19, 2017
• Primary Completion: December 19, 2018
• Study Completion: May 29, 2020
• Last Updated: February 22, 2024
• Results First Posted: February 22, 2024

Record last verified: 2024-02

Locations

US (1)