Clinical Trial to Assess the Efficacy and Toxicity of Induction and Consolidation With CPX-351 for Patients Aged 60 to 75 Years With Secondary or High-risk Acute Myeloid Leukemia

NCT04230239 | Completed Phase 2

• 2 other identifiers: LAMVYX2018-004353-24
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 12

Brief Summary

This protocol corresponds to a prospective, multicentre, open label, phase II study designed to evaluate the efficacy of CPX-351 in elderly patients with secondary or high-risk AML. The clinical trial is divided into pre-treatment, treatment (induction and consolidation cycles) and follow-up periods and consists of a single arm group. Patients will be enrolled at diagnosis to follow the treatment arm. After that will start induction chemotherapy with CPX-351 regimen (14 days maximum screening period). Once a patient have been evaluated for response and recovered from major complications, he/she will start second course (consolidation 1), unless the bone marrow and peripheral blood assessment is showing less than a complete response, then a second induction may be offered. If a CR or CRi is obtained after the second induction course, patients will start the third course after a rest and recovery period. Patients aged between 60 and 65 years old are recommended to undergo an allo-SCT after first consolidation if they are considered fit for this procedure and they have a full matched related or unrelated donor. Patients aged between 65 and 70 years old can be proposed for an allo-SCT in CR/CRi if they have a composite HSCT co-morbidity index /age less than 4 and a suitable fully matched related donor. In patients over 70 years old, an allo-SCT in first CR should be avoided although the decision should be taken on an individual basis. Patients with CR/CRi who are not considered for an allo-SCT, will follow 6 maintenance cycles with modified courses of CPX-351 schedule. Patients showing unacceptable toxicity along all therapeutic phases that, in consideration of the investigator, will be prematurely discontinued. All patients will be followed-up for survival. The study will be analyzed on an intention to treat basis. Bone marrow and response assessments will be done after each induction and consolidation course, and every 3 months during the first 12 months after starting maintenance therapy. Patients will be followed-up for a minimum period of 1 year after the enrolment of the last patient. Additionally, after the end of the trial, patients will be followed-up for 2 years in order to verify survival and the evolution of the disease. Study design allows a maximum of 59 patients.

Conditions

Newly Diagnosed Secondary or High Risk AML

Keywords

Secondary AML; High risk AML

Outcome Measures

Primary Outcomes (1)

• To evaluate the CR/CRi rate after induction with CPX-351

  The primary endpoint of the study is to evaluate the CR/CRi rate after induction with CPX-351. The responses for CR, CRi, PR, therapeutic failure, and disease recurrence are defined for this study based on the revised recommendations of the International Working Group for response criteria.

  After 1 or 2 cycles of induction (between 12 and 16 weeks approximately)

Secondary Outcomes (15)

• Incidence of Treatment-Adverse Events (Safety and Tolerability) of the CPX-351 induction regimen.

  The induction cycles (up to 2 cycles) will have a mean estimated duration of 6 weeks per cycle. Safety/toxicity assessments will be done in day 1, 8, 15, 22, 29 and 36 of the induction cycles.

• To evaluate the effect of priming with G-CSF with the CPX-351 regimen

  Priming with G-CSF will be done in the induction cycles (up to 2 cycles) and in the consolidation cycles (up to 2 cycles) that will have an an estimated duration of 6 weeks per cycle.

• Incidence of Treatment-Adverse Events (Safety and Tolerability) of the CPX-351 consolidation regimen

  Safety/toxicity assessments will be done in day 1, 8, 15, 22, 29 and 36 of the consolidation cycles

• Incidence of Treatment-Adverse Events (Safety and Tolerability) of the CPX-351 maintenance regimen

  Safety/toxicity assessments will be done every 2 weeks during the manteinance cycles (24 to 40 weeks of maintenance).

• Overall survival

  Estimated 1, 2 and 3 year OS

Study Arms (1)

CPX-351

EXPERIMENTAL

Drug: CPX-351

Interventions

CPX-351 DRUG

CPX-351 has IV administration Vyxeos contains 2.2 mg/mL and 5 mg/mL powder for concentrate for solution for infusion of Daunorubicin and cytarabine. Each vial contains 44 mg of daunorubicin and 100 mg of cytarabine. After reconstitution, the solution contains 2.2 mg/mL daunorubicin and 5 mg/mL cytarabine

CPX-351

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure. Informed consent form must be signed by the patient and the investigator.
• Age 60 to 75 years at the time of diagnosis of AML.
• Newly confirmed diagnosed of AML according to WHO 2008 criteria.
• Secondary or high risk AML, defined as one of the following:
• t-AML: documentation of prior cytotoxic therapy or radiation therapy for an unrelated disease in a discharge summary or pharmacy records or radiation therapy records
• MDSAML: bone marrow documentation of MDS prior to diagnosis of AML (could have been treated previously with hypomethylating or standard chemotherapy)
• CMMoLAML: bone marrow documentation of CMMoL prior to diagnosis of AML (could have been treated previously with hypomethylating or standard chemotherapy)
• de novoAML with FISH or cytogenetic changes linked to MDS per WHO 2016 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Ability to adhere to the study visit schedule and other protocol requirements.
• Laboratory values fulfilling the following:
• Serum creatinine \< 2.0 mg/mL
• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin \< 3 times the upper limit of normal (ULN, subjects with elevated liver enzymes related to disease were instructed to contact the Sponsor) (subjects with Gilbert's Syndrome were instructed to contact the sponsor).
• Subjects with second malignancies in remission may have been eligible if there was clinical evidence of disease stability for a period ≥ 6 months off cytotoxic chemotherapy, documented by imaging, tumor marker studies at screening. Subjects maintained on long-term nonchemotherapy treatment such as hormonal therapy were eligible.
• Cardiac ejection fraction ≥ 50% assessed by echocardiography or MUGA.

You may not qualify if:

• Patients with genetic diagnosis of acute promyelocytic leukemia.
• Age \<60 years or \>75 years.
• Blastic phase of bcr/abl chronic myeloid leukemia.
• Patients with de novo AML without FISH or cytogenetic changes linked to MDS per WHO 2016 criteria.
• Clinical evidence of active central nervous system (CNS) leukemia.
• Subjects with active (uncontrolled, metastatic) second malignancies.
• Any major surgery or radiation therapy in 4 weeks.
• Subjects with myocardial impairment of any cause (eg, 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).
• Uncontrolled infection; subjects with an infection receiving treatment (antibiotic, antifungal, or antiviral treatment) could be entered into the study provided the subject was respiratory and hemodynamically stable for ≥ 72 hours.
• Current evidence of invasive fungal infection (blood or tissue culture); subjects with recent fungal infection must have had 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.
• Serum creatinine ≥ 20 mg/dL (unless it is attributable to AML activity).
• Bilirubin, alkaline phosphatase, or SGOT \> 3 times the ULN (unless it is attributable to AML activity).
• Subjects with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent).
• History of Wilson's disease or other copper-metabolism disorder.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (12)

Institut Català D'Oncologia-Hospital Germans Trias I Pujol

Badalona, Spain

Location

Institut Català D'Oncologia - Hospital Duran I Reynals

Bellvitge, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, Spain

Location

Hospital Universitario de Gran Canaria Dr. Negrín

Las Palmas, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, Spain

Location

Hospital Ramón Y Cajal

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Spain

Location

Hospital General Del H.U. Virgen Del Rocío

Seville, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Hospital Universitario Y Politécnico La Fe

Valencia, Spain

Location

Related Publications (15)

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  BACKGROUND

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MeSH Terms

Interventions

CPX-351

Study Officials

• Pau Montesinos Fernández, PhD

  Hospital Universitario La Fe

  PRINCIPAL INVESTIGATOR

• José Antonio Pérez Simón, PhD

  Hospitales Universitarios Virgen del Rocío

  PRINCIPAL INVESTIGATOR

• Carmen López-Carrero García

  Fundación Pethema

  STUDY CHAIR

Study Design

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

Model Details: This protocol corresponds to a prospective, multicenter, open-label, phase II study to assess efficacy of CPX-351 in elderly patients (60 to 75 years of age) with newly diagnosed high risk AML. In the context of this protocol, a treatment cycle is defined as the first day of study drug administration (Day 1) up to and including the day before the first day of the treatment cycle immediately afterwards. The treatment cycles will begin after Day 42 but no later than Day 80, counting from Day 1 of the treatment cycle immediately before. Treatment cycles may be administered while the patient is hospitalized. Patients will receive a maximum of 4 treatment cycles (up to 2 inductions and 2 consolidations) and 6 maintenance cycles. Clinical conditions in the care of patients with acute leukemia require the need for flexibility. However, deviations from the study treatment defined in this section must be prospectively discussed with the coordinator.

Study Record Dates

• First Submitted: November 21, 2019
• First Posted: January 18, 2020
• Study Start: December 26, 2019
• Primary Completion: April 30, 2021
• Study Completion: August 11, 2021
• Last Updated: September 8, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (12)