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TerminatedNCT04425655Updated Sep 22, 2022

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

A Phase 2 interventional study of Fludarabine and Vyxeos in Acute Myeloid Leukemia, Adult, AML and AML, Adult, sponsored by University of California, San Diego. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-09-22.

Sponsored by University of California, San Diego · Phase 2, Interventional, and Treatment

Why this study was terminated
Original investigator for the trial has left

From the registry’s dates

  • Primary completion was Jul 2022, 4 years 3 months ago, and no results have been posted to the registry.
Phase
Phase 2
Study type
Interventional
Enrollment
2
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

This is a phase 2, open label single arm study to look at the effectives and safety of fludarabine in combination with CPX-351 in patients with untreated AML. The rationale for this combination stems from data which indicated that pre-treatment of the THP-1 cell line with fludarabine for 4 hours prior to CPX-351 administration (Flu-CPX) significantly potentiated intracellular ara-CTP accumulation compared to CPX-351 alone. This suggests that fludarabine combined with CPX-351 may have efficacy against leukemic clones that would be resistant to CPX-351 or standard chemotherapy in first induction. It has been demonstrated that treatment with CPX-351 produces superior clinical outcomes in secondary AML likely due to its novel formulation, which results in sustained exposure of the cytotoxic agents cytarabine and daunorubicin in a synergistic 5:1 ratio within the plasma and bone marrow. Fludarabine can potentially improve upon the outcomes observed with CPX-351 monotherapy and 7+3 by enhancing intracellular ara-CTP accumulation from CPX-351. Patients will received fludarabine and CPX-351 for up to 2 cycles of induction and 2 cycles of consolidation.

02

Conditions studied

  • Acute Myeloid Leukemia, Adult
  • AML
  • AML, Adult

Keywords

  • Vyxeos
  • CPX-351
  • Fludarabine
  • Untreated AML
03

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 2 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

University of California, San Diego is the lead sponsor of 958 studies on the registry; 191 are open to participants now.

Of its 110 completed or terminated interventional studies of FDA-regulated products, 70 (64%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Histologically confirmed de novo or secondary AML as defined by WHO criteria
  2. Intermediate- or poor-risk disease by ELN 2017 criteria
  3. Adults 18 years of age or older
  4. ECOG performance status of 0, 1, or 2
  5. Able to give informed consent and follow study guidelines

  6. Organ function requirements:

    1. Adequate renal function defined as creatinine clearance greater than 60 ml/min
    2. 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.
    3. ALT/AST less than or equal to 3 times the upper limit of normal
    4. LVEF 50 percent by echocardiogram or MUGA
  7. 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.
  8. 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.
  9. Women of child-bearing potential has negative pregnancy test prior to initiating study drug dosing.

Exclusion criteria

Exclusion Criteria:

  1. Current or anticipated use of additional investigational agents.
  2. 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.
  3. 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.
  4. Favorable risk cytogenetics as defined by 2017 ELN risk stratification including acute promyelocytic leukemia
  5. Chronic myeloid leukemia in myeloid blast crisis
  6. 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
  7. Clinical evidence of active CNS leukemia
  8. Active or metastatic second malignancy
  9. Any major surgery or radiation therapy within four weeks.
  10. Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent).
  11. Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent
  12. 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)
  13. 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.
  14. Current evidence of invasive fungal infection (blood or tissue culture); patients with recent fungal infection must have subsequent negative culture(s) to be eligible
  15. Known HIV infection
  16. Active hepatitis B or hepatitis C infection
  17. Hypersensitivity to cytarabine, daunorubicin or liposomal products
  18. History of Wilson's disease or copper-metabolism disorder
  19. Pregnant or breastfeeding
  20. Any condition which in the opinion of the investigator will interfere with the ability of the subject to comply with the requirements of the study
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
2 participants (actual)

Study arms

  • Experimental
    Fludarabine and CPX351

    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

  • DrugFludarabine

    30mg/m2 days 1 through 5

    Also known as: Oforta, Fludara

  • DrugVyxeos

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

    Also known as: CPX-351

06

What researchers measure

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.

    Time frame: 35 days

Secondary outcomes

  1. Safety and Tolerability

    Safety and tolerability will be determined by rates of NCI CTCAE 5.0 Grade 3-5 toxicities and rate of discontinuation from study therapy due to intolerance

    Time frame: 6 months

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

    Safety and tolerability will be determined by rates of NCI CTCAE 5.0 Grade 3 toxicities and rate of discontinuation from study therapy due to intolerance

    Time frame: 6 months

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

    Safety and tolerability will be determined by rates of NCI CTCAE 5.0 Grade 4 toxicities and rate of discontinuation from study therapy due to intolerance

    Time frame: 6 months

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

    Safety and tolerability will be determined by rates of NCI CTCAE 5.0 Grade 5 toxicities and rate of discontinuation from study therapy due to intolerance

    Time frame: 6 months

  5. CR Rate

    CR rate defined as proportion of patients achieving a CR after 1-2 cycles of induction

    Time frame: 60 days

  6. Overall response rate

    Overall response rate (CR +CRi) after 1 cycle of induction

    Time frame: 35 days

  7. Overall survival

    Overall survival (OS) at 1 year, with OS defined as time from start of study therapy to death from any cause

    Time frame: 1 year

  8. Overall survival

    Overall survival (OS) at 3 years, with OS defined as time from start of study therapy to death from any cause

    Time frame: 3 years

  9. Leukemia-free survival

    Leukemia-free survival (LFS) at 1 year, with EFS defined as the time from start of study therapy until failure to attain CR, relapse, or death from any cause

    Time frame: 1 years

  10. Leukemia-free survival

    Leukemia-free survival (LFS) at 3 years, with EFS defined as the time from start of study therapy until failure to attain CR, relapse, or death from any cause

    Time frame: 3 years

  11. Event free survival

    Event Free Survival (EFS) at 1 year, with EFS defined as the time from start of study therapy until failure to attain CR, relapse, or death from any cause.

    Time frame: 1 year

  12. Event free survival

    Event Free Survival (EFS) at 3 years, with EFS defined as the time from start of study therapy until failure to attain CR, relapse, or death from any cause.

    Time frame: 3 years

  13. Platelet Recovery

    Platelet recovery, defined as the time from start of study therapy until absolute neutrophil count \>1,000/mcl in patients achieving a CR

    Time frame: 60 days

  14. 30-day

    30-day mortality defined as death from any cause within 30 days of starting study therapy

    Time frame: 30 days from start of study therapy

  15. 60-day mortality

    60-day mortality defined as death from any cause within 60 days of starting study therapy

    Time frame: 60 days from start of study therapy

Other outcomes

  1. Minimal Residual Disease (MRD) Response (positive or negative)

    MRD response at CR/CRi will be assessed by multiparameter flow cytometry at the University of Washington.

    Time frame: 60 days

  2. Descriptive Statistics of Patients Mutation Profile at Screening

    Somatic mutation profile as determined by next generation sequencing will be performed for recurrent AML mutations using standard technique used at individual sites (local or send-out testing)

    Time frame: At Screening

  3. Descriptive Statistics of Patients Mutation Profile at Relapse

    Somatic mutation profile as determined by next generation sequencing will be performed for recurrent AML mutations using standard technique.

    Time frame: At Relapse

07

Study locations

1 site
  • UCSD Moores Cancer Center
    La Jolla, California 92093, United States
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 22, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT04425655
Lead sponsor
University of California, San Diego
Collaborators
Jazz Pharmaceuticals
Responsible party
James Mangan (Associate Clinical Professor of Medicine, University of California, San Diego) — Principal investigator
First posted
Jun 11, 2020
Start date
Aug 5, 2020
Primary completion
Jul 1, 2022
Completion
Jul 1, 2022
Last update
Sep 22, 2022

Study contacts

Matthew Wieduwilt, MD, PhD
study chair · UC San Diego

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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