Fludarabine in Combination With Daunorubicin and Cytarabine Liposome in Newly-diagnosed Acute Myeloid Leukemia.

NCT04425655 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: UCHMC1914
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 2 clinical trial will evaluate the effectiveness and safety of fludarabine in combination with CPX-351 in patients with untreated AML. Patients will receive fludarabine and CPX-351 during Induction 1 and 2 as well as 2 cycles of consolidation therapy.

Conditions

Acute Myeloid Leukemia, Adult; AML; AML, Adult

Keywords

Vyxeos; CPX-351; Fludarabine; Untreated AML

Outcome Measures

Primary Outcomes (1)

• Overall response rate after induction

  Overall response rate after induction, defined as the sum of complete response (CR) rate and complete response with incomplete count recovery (CRi) rate after 1-2 cycles of induction therapy, in accordance with 2017 ELN criteria.

  35 days

Secondary Outcomes (15)

• Safety and Tolerability

  6 months

• Incidence of Grade 3 Treatment Emergent Adverse Events [Safety and Tolerability]

  6 months

• Incidence of Grade 4 Treatment Emergent Adverse Events [Safety and Tolerability]

  6 months

• Incidence of Grade 5 Treatment Emergent Adverse Events [Safety and Tolerability]

  6 months

• CR Rate

  60 days

Other Outcomes (3)

• Minimal Residual Disease (MRD) Response (positive or negative)

  60 days

• Descriptive Statistics of Patients Mutation Profile at Screening

  At Screening

• Descriptive Statistics of Patients Mutation Profile at Relapse

  At Relapse

Study Arms (1)

Fludarabine and CPX351

EXPERIMENTAL

Induction 1: Fludarabine 30 mg/m2/day IV on days 1-5 for 5 doses Daunorubicin and cytarabine liposome (CPX-351) daunorubicin 44 mg/m2/day and cytarabine 100 mg/m2/day IV on days 1, 3, 5 (given 4 hours after fludarabine infusion) for 3 doses Induction 2 (residual leukemia after Induction 1): Fludarabine 30 mg/m2/day IV on days 1-3 for 3 doses Daunorubicin and cytarabine liposome (CPX-351) daunorubicin 44 mg/m2/day and cytarabine 100 mg/m2/day IV on days 1, 3 (given 4 hours after fludarabine infusion) for 2 doses Optional consolidation, up to 2 cycles: Daunorubicin and cytarabine liposome (CPX-351) daunorubicin 29 mg/m2/day and cytarabine 65 mg/m2/day IV on days 1, 3 for 2 doses

Drug: Fludarabine; Drug: Vyxeos

Interventions

Fludarabine DRUG

30mg/m2 days 1 through 5

Also known as: Oforta, Fludara

Fludarabine and CPX351

Vyxeos DRUG

100U/m2 days 1, 3 5 in induction, 65U/m2 days 1 and 3 for consolidation

Also known as: CPX-351

Fludarabine and CPX351

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed de novo or secondary AML as defined by WHO criteria
• Intermediate- or poor-risk disease by ELN 2017 criteria
• Adults 18 years of age or older
• ECOG performance status of 0, 1, or 2
• Able to give informed consent and follow study guidelines
• Organ function requirements:
• Adequate renal function defined as creatinine clearance greater than 60 ml/min
• Adequate hepatic function defined by serum bilirubin less than or equal 2 mg/dL. If serum bilirubin greater than 2 mg/dl and direct bilirubin is less than 30 percent of total bilirubin contact study chair for eligibility exception for Gilbert's syndrome.
• ALT/AST less than or equal to 3 times the upper limit of normal
• LVEF 50 percent by echocardiogram or MUGA
• Patients with history of second malignancies in complete remission and without history of metastasis are eligible if there is clinical evidence of disease stability for a period of greater than 6 months off cytotoxic chemotherapy, documented by imaging, tumor marker studies, etc., at screening.
• Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 120 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Women of child-bearing potential has negative pregnancy test prior to initiating study drug dosing.

You may not qualify if:

• Current or anticipated use of additional investigational agents.
• Any prior treatment for AML with the exception of corticosteroids, hydroxyurea, and/or leukapheresis to prevent or treat early complications prior to starting study therapy. Permitted prior therapy must be stopped 24 hours prior to starting study therapy.
• Prior use of hypomethylating agents is permitted for patients with history of antecedent MDS. Last dose of hypomethylating therapy must have been 15 or more days prior to starting study therapy. Toxicities associated with prior MDS therapy must have recovered to grade 1 or less prior to start of treatment.
• Favorable risk cytogenetics as defined by 2017 ELN risk stratification including acute promyelocytic leukemia
• Chronic myeloid leukemia in myeloid blast crisis
• Except for CMML, patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible
• Clinical evidence of active CNS leukemia
• Active or metastatic second malignancy
• Any major surgery or radiation therapy within four weeks.
• 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 greater than or equal to 72 hrs.
• Current evidence of invasive fungal infection (blood or tissue culture); patients with recent fungal infection must have subsequent negative culture(s) to be eligible
• Known HIV infection

Sponsors & Collaborators

• University of California, San Diego: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

fludarabine; fludarabine phosphate; CPX-351

Condition Hierarchy (Ancestors)

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

Study Officials

• Matthew Wieduwilt, MD, PhD

  UC San Diego

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor of Medicine

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 11, 2020
• Study Start: August 5, 2020
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2022
• Last Updated: September 22, 2022

Record last verified: 2022-09

Locations

US (1)