- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04425655
Fludarabine in Combination With Daunorubicin and Cytarabine Liposome in Newly-diagnosed Acute Myeloid Leukemia.
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
La Jolla, California, United States, 92093
- UCSD Moores Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 |
30mg/m2 days 1 through 5
Other Names:
100U/m2 days 1, 3 5 in induction, 65U/m2 days 1 and 3 for consolidation
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate after induction
Time Frame: 35 days
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and Tolerability
Time Frame: 6 months
|
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
|
6 months
|
Incidence of Grade 3 Treatment Emergent Adverse Events [Safety and Tolerability]
Time Frame: 6 months
|
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
|
6 months
|
Incidence of Grade 4 Treatment Emergent Adverse Events [Safety and Tolerability]
Time Frame: 6 months
|
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
|
6 months
|
Incidence of Grade 5 Treatment Emergent Adverse Events [Safety and Tolerability]
Time Frame: 6 months
|
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
|
6 months
|
CR Rate
Time Frame: 60 days
|
CR rate defined as proportion of patients achieving a CR after 1-2 cycles of induction
|
60 days
|
Overall response rate
Time Frame: 35 days
|
Overall response rate (CR +CRi) after 1 cycle of induction
|
35 days
|
Overall survival
Time Frame: 1 year
|
Overall survival (OS) at 1 year, with OS defined as time from start of study therapy to death from any cause
|
1 year
|
Overall survival
Time Frame: 3 years
|
Overall survival (OS) at 3 years, with OS defined as time from start of study therapy to death from any cause
|
3 years
|
Leukemia-free survival
Time Frame: 1 years
|
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
|
1 years
|
Leukemia-free survival
Time Frame: 3 years
|
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
|
3 years
|
Event free survival
Time Frame: 1 year
|
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.
|
1 year
|
Event free survival
Time Frame: 3 years
|
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.
|
3 years
|
Platelet Recovery
Time Frame: 60 days
|
Platelet recovery, defined as the time from start of study therapy until absolute neutrophil count >1,000/mcl in patients achieving a CR
|
60 days
|
30-day
Time Frame: 30 days from start of study therapy
|
30-day mortality defined as death from any cause within 30 days of starting study therapy
|
30 days from start of study therapy
|
60-day mortality
Time Frame: 60 days from start of study therapy
|
60-day mortality defined as death from any cause within 60 days of starting study therapy
|
60 days from start of study therapy
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Minimal Residual Disease (MRD) Response (positive or negative)
Time Frame: 60 days
|
MRD response at CR/CRi will be assessed by multiparameter flow cytometry at the University of Washington.
|
60 days
|
Descriptive Statistics of Patients Mutation Profile at Screening
Time Frame: 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)
|
At Screening
|
Descriptive Statistics of Patients Mutation Profile at Relapse
Time Frame: At Relapse
|
Somatic mutation profile as determined by next generation sequencing will be performed for recurrent AML mutations using standard technique.
|
At Relapse
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Matthew Wieduwilt, MD, PhD, UC San Diego
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UCHMC1914
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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