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Acute Myeloid Leukemia, AdultPhase 2NCT04425655

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

A Phase 2 study testing Fludarabine and Vyxeos in people with Acute Myeloid Leukemia, Adult and AML, run by University of California, San Diego at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia, Adult, AML, AML, Adult
What is being tested?
Fludarabine and Vyxeos
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
5 Aug 2020to 1 Jul 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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
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  • 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
  • Active hepatitis B or hepatitis C infection
  • Hypersensitivity to cytarabine, daunorubicin or liposomal products
  • History of Wilson's disease or copper-metabolism disorder
  • Pregnant or breastfeeding
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UCSD Moores Cancer Center

    La Jolla, California, 92093

Other trials in United States

About this study

Official title: A Phase II Trial of Fludarabine in Combination With Daunorubicin and Cytarabine Liposome for Adults With Newly-diagnosed Acute Myeloid Leukemia: University of California Hematologic Malignancies Consortium Protocol 1914

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.

Being tested
Fludarabine, Vyxeos
Keywords
Vyxeos, CPX-351, Fludarabine, Untreated AML
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FludarabineDrug

    Also called Oforta, Fludara

    30mg/m2 days 1 through 5

  • VyxeosDrug

    Also called CPX-351

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

Study groups in NCT04425655
Study groupRoleWhat they receive
Fludarabine and CPX351ExperimentalInduction 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
Receives: Drug: Fludarabine; Drug: Vyxeos

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 35 days

Secondary outcomes (15)

  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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 6 months

  5. CR Rate

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

    Measured: 60 days

  6. Overall response rate

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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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.

    Measured: 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.

    Measured: 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

    Measured: 60 days

  14. 30-day

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

    Measured: 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

    Measured: 60 days from start of study therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jun 2020
  2. Study start5 Aug 2020
  3. Primary completion1 Jul 2022
  4. Study completion1 Jul 2022

Why it stopped: Original investigator for the trial has left

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04425655
Sponsor's protocol ID
UCHMC1914
Status last verified
Sep 2022
First submitted
3 Jun 2020
Last updated
22 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludarabine and Vyxeos in people with Acute Myeloid Leukemia, Adult and AML, run by University of California, San Diego at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Original investigator for the trial has left). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate after induction (time frame: 35 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04425655.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2022.

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