FLT PET/CT in Measuring Response in Patients With Previously Untreated Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This phase II trial studies fluorothymidine F 18 (FLT) positron emission tomography (PET)/computed tomography (CT) in measuring response in patients with previously untreated acute myeloid leukemia. FLT is a radioactive substance that may light up where cancer is in the body. FLT is injected into the blood and builds up in cells that are dividing, including cancer cells. Diagnostic procedures, such as PET/CT, may help measure a patient's response to earlier treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the negative predictive value (NPV) of post-treatment FLT PET/CT imaging for complete remission (CR) in patients receiving induction chemotherapy for acute myeloid leukemia (AML). SECONDARY OBJECTIVES: I. To evaluate the positive predictive value (PPV) of post-treatment FLT PET/CT imaging for complete remission. II. To estimate the sensitivity and specificity of FLT PET/CT at complete remission detection. III. To evaluate pre-treatment FLT PET/CT activity as a predictor of complete remission. IV. To evaluate the change between pre-treatment and post-treatment FLT PET/CT activity as a predictor of complete remission. V. To correlate post-treatment FLT PET/CT imaging parameters with day 28 bone marrow aspirate/biopsy and minimal residual disease assessment by flow cytometry. VI. To correlate FLT PET/CT imaging parameters (maximum FLT uptake across the total bone marrow compartment [SUVmax], mean FLT uptake across the total bone marrow compartment [SUVmean], heterogeneity) with biologic correlates (minimal residual disease [MRD] assessment). OUTLINE: Patients receive anthracycline intravenously (IV) on days 1-3 and cytarabine IV on days 1-7 for up to 2 courses. Patients then undergo FLT PET/CT within 3 days before or after the nadir bone marrow biopsy (between days 10-17 after initiation of first induction cycle and prior to reinduction). Patients may undergo an optional FLT PET/CT prior to induction chemotherapy if it does not interfere with commencement of treatment. After completion of study, patients are followed up at day 28-35.

Official Title
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Early Assessment of Treatment Response in AML Using FLT PET/CT Imaging

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Chemotherapy
* Procedure: Computed Tomography
* Drug: Cytarabine
* Other: Fluorothymidine F-18
* Other: Laboratory Biomarker Analysis
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have previously untreated AML and be candidates for intensive induction chemotherapy; patients are allowed to have had prior hydroxyurea Patients must not have acute promyelocytic leukemia (APL) and must not have evidence of t(15;17)(q22;q21) Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 (restricted to ECOG performance status [PS] 0-2 if age > 70 years) Patients must have left ventricular ejection fraction (LVEF) > 45% or within institutional normal limits Patients must be able to lie still for a 1.5 hour PET scan Patient must NOT have a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-fluorothymidine Patient must NOT weigh more than the maximum weight limit for the PET/CT table for the scanner(s) to be used at each center The patient is participating in the trial at an institution which has agreed to perform the imaging research studies, completed the ECOG-American College of Radiology Imaging Network (ACRIN) defined scanner qualification procedures and received ECOG-ACRIN approval as outlined Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (anthracycline, cytarabine, FLT PET/CT)<br>Patients receive anthracycline IV on days 1-3 and cytarabine IV on days 1-7 for up to 2 courses. Patients then undergo FLT PET/CT within 3 days before or after the nadir bone marrow biopsy (between days 10-17 after initiation of first induction cycle and prior to reinduction). Patients may undergo an optional FLT PET/CT prior to induction chemotherapy if it does not interfere with commencement of treatment. | Drug: Chemotherapy<br>* Given anthracycline IV<br>* Other names: Chemotherapy, Cancer, General;Procedure: Computed Tomography<br>* Undergo FLT PET/CT<br>* Other names: tomography;Drug: Cytarabine<br>* Given IV<br>* Other names: WR-28453;Other: Fluorothymidine F-18<br>* Undergo FLT PET/CT<br>* Other names: Fluorothymidine F 18;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Positron Emission Tomography<br>* Undergo FLT PET/CT<br>* Other names: PT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negative predictive value of post-treatment FLT PET/CT imaging for CR in comparison with blast counts from bone marrow biopsy (BMBX) | Three imaging parameters (SUVmean, SUVmax, heterogeneity of FLT uptake [SUVhetero]) will be measured from an FLT PET/CT scan and SUVmax will be the primary endpoint. The binomial proportion of PPV and the corresponding Exact confidence intervals will be calculated. In addition, the calculated NPV will be tested against the null hypothesis to see if it's significantly larger than 0.64 (NPV of day-14 BMBX in CR prediction). | Up to day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PPV of post-treatment FLT PET/CT imaging for complete remission | The binomial proportion of PPV and the corresponding Exact confidence intervals will be calculated. In addition, the calculated PPV will be tested to see if it's significantly larger than 0.79 (PPV of day-14 BMBX in CR prediction). | Up to day 35 | 
| Sensitivity of FLT PET/CT for complete remission detection | The binomial proportions and the corresponding Exact confidence intervals will be calculated for sensitivity estimation. | Up to day 35 | 
| Specificity of FLT PET/CT for complete remission detection | The binomial proportions and the corresponding Exact confidence intervals will be calculated for specificity estimation. | Up to day 35 | 
| Pre-treatment FLT PET/CT activity as a predictor of complete remission | The receiver operating characteristic (ROC) approach will be used to test the continue measurement of this variable in predicting CR. | Baseline | 
| Change between pre-treatment and post-treatment FLT PET/CT activity as a predictor of complete remission | The ROC approach will be used to test the continue measurement of this variable in predicting CR. | Baseline to up to day 35 | 
| Biologic correlates of AML (MRD assessment) | Correlation of FLT PET/CT imaging parameters (SUVmax, SUVmean, SUVhetero) with biologic correlates will be studied and regression analysis will be used to assess this aim. | At day 14 |