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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Cytarabine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Drug: Chemotherapy; Procedure: Computed Tomography; Other: Fluorothymidine F-18; Procedure: Positron Emission Tomography; Procedure: Bone Marrow Aspiration

Detailed Description

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 post-treatment FLT PET/CT imaging for detecting complete remission.

III. To correlate FLT PET/CT imaging with biologic correlates (minimal residual disease [MRD] assessment) IV. To correlate FLT PET/CT imaging with relapse-free survival and overall survival.

EXPLORATORY OBJECTIVES:

III. To evaluate pre-treatment FLT PET/CT imaging as a predictor of complete remission.

IV. To evaluate the change between pre-treatment and post-treatment FLT PET/CT imaging as a predictor of complete remission.

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. Patients also undergo bone marrow biopsy and aspiration and blood sample collection during screening and on the trial.

After completion of study, patients are followed up at day 28-35, and then up to 1 year beyond the end of study accrual period.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center - University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic (anthracycline, cytarabine, FLT PET/CT); 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. Patients also undergo bone marrow biopsy and aspiration and blood sample collection during screening and on the trial.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Cytarabine; Given IV; Other Names: .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Procedure: Bone Marrow Biopsy; Undergo bone marrow biopsy and aspiration; Other Names: Biopsy of Bone Marrow; Biopsy, Bone Marrow; Drug: Chemotherapy; Given anthracycline IV; Other Names: Chemo; Chemotherapy (NOS); Chemotherapy, Cancer, General; Procedure: Computed Tomography; Undergo FLT PET/CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Other: Fluorothymidine F-18; Undergo FLT PET/CT; Other Names: 18F-FLT; 3'-deoxy-3'-[18F]fluorothymidine; 3'-Deoxy-3'-(18F) Fluorothymidine; Fluorothymidine F 18; ALOVUDINE F-18; Procedure: Positron Emission Tomography; Undergo FLT PET/CT; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Bone Marrow Aspiration; Undergo bone marrow biopsy and aspiration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Negative Predictive Value of Post-treatment Fluorothymidine F 18 (FLT) Positron Emission Tomography (PET)/Computed Tomography (CT) Imaging for Complete Remission (CR) in Comparison With Blast Counts From Bone Marrow Biopsy (BMBX)	Three imaging parameters (standardized uptake value [SUV]mean, SUVmax, heterogeneity of FLT uptake [SUVhetero]) will be measured from an FLT PET/CT scan and SUVmax will be the primary endpoint. Higher values of SUVmax assume to indicate a non-response the therapy and a cut point of 7 (SUVmax >7) will be used as the threshold indicating a negative scan. The binomial proportion of negative predictive value (NPV) 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). CR:Complete remission CRi: Complete remission with incomplete platelet recovery LFS: Leukemia-free state Non-responders defined as Not (CR,CRi,or LFS) Negative predictive value (NPV) of the post-treatment FLT PET/CT scan is Probability ((not CR,CRi,or LFS) │ SUVmax >7 )	Up to day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Predictive Value (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 Post-treatment FLT PET/CT for Detecting Complete Remission (a Clinical Response of CR, CRi, or LFS )	The binomial proportions and the corresponding exact confidence intervals will be calculated for sensitivity estimation where FLT Test : Negative: SUV >7; Positive: SUV<=7 Clinical Response: Negative: not (CR, CRi, or LFS); Positive (Responders): CR, CRi, or LFS	Up to day 35
Specificity of Post-treatment FLT PET/CT for Detecting Complete Remission	The binomial proportions and the corresponding exact confidence intervals will be calculated for specificity estimation. Test response: Negative: SUV >7; Positive: SUV<=7 Clinical Response = Complete remissions: Negative (Non-Responders): not (CR, CRi, or LFS); Positive (Responders): CR, CRi, or LFS	Up to day 35
FLT PET/CT Imaging Parameters With Biologic Correlates (Minimal Residual Disease Assessment)	FLT PET/CT imaging features will be compared with biologic correlates (minimal residual disease [MRD] assessment).	Up to day 35
FLT PET/CT Imaging to Predict Relapse-free Survival	compare the Recurrence-Free Survival (RFS) between positive and negative post-treatment FLT PET/CT scans, where an SUVmax less than or equal to 7 (i.e., low FLT uptake) was considered a positive result, and an SUVmax greater than 7 (i.e., high FLT uptake) was a negative result. Participants were followed for survival outcomes until study closure when the last participant has been followed for 1 year after study enrollment. The relapse endpoint included both reappearance of blasts in the blood; and presence of more than 5% blasts not attributable to another cause Time-to-relapse was measured from the date of the remission bone marrow biopsy to the date of first recurrence or death, whichever came first. RFS was only evaluable for participants with a clinical response of CR, CRi, or LFS at the remission bone marrow biopsy.	Up to day 35 and up to 4 years for RFS
FLT PET/CT Imaging to Predict Overall Survival	compare the Overall Survival (OS) between positive and negative post-treatment FLT PET/CT scans, where an SUVmax<= 7 (i.e., low FLT uptake) was considered a positive result, and an SUVmax > 7 (i.e., high FLT uptake) was a negative result. Participants were followed for survival outcomes until study closure when the last participant has been followed for 1 year after study enrollment.	Up to day 35 and up to 4 years for RFS

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Robert Jeraj, ECOG-ACRIN Cancer Research Group

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2016
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): February 13, 2027

Study Registration Dates

• First Submitted: March 18, 2015
• First Submitted That Met QC Criteria: March 18, 2015
• First Posted (Estimated): March 19, 2015

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Nucleic Acids, Nucleotides, and Nucleosides; Cytodiagnosis; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Nucleosides; Arabinonucleosides; Cytarabine; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Drug Therapy; alovudine
• Other Study ID Numbers: NCI-2015-00328 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180820 (U.S. NIH Grant/Contract); EAI141 (Other Identifier: CTEP); U10CA180827 (U.S. NIH Grant/Contract)