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

Primary Purpose

Acute Myeloid Leukemia

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Chemotherapy
Computed Tomography
Cytarabine
Fluorothymidine F-18
Laboratory Biomarker Analysis
Positron Emission Tomography
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University of Alabama at Birmingham Cancer Center
  • Mayo Clinic in Rochester
  • Washington University School of Medicine
  • Mount Sinai Hospital
  • UNC Lineberger Comprehensive Cancer Center
  • University of Oklahoma Health Sciences Center
  • University of Pennsylvania/Abramson Cancer Center
  • Fox Chase Cancer Center
  • Vanderbilt University/Ingram Cancer Center
  • UT Southwestern/Simmons Cancer Center-Dallas
  • Huntsman Cancer Institute/University of Utah
  • University of Wisconsin Carbone Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diagnostic (anthracycline, cytarabine, FLT PET/CT)

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).
Sensitivity of FLT PET/CT for complete remission detection
The binomial proportions and the corresponding Exact confidence intervals will be calculated for sensitivity estimation.
Specificity of FLT PET/CT for complete remission detection
The binomial proportions and the corresponding Exact confidence intervals will be calculated for specificity estimation.
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.
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.
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.

Full Information

First Posted
March 18, 2015
Last Updated
July 8, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02392429
Brief Title
FLT PET/CT in Measuring Response in Patients With Previously Untreated Acute Myeloid Leukemia
Official Title
Early Assessment of Treatment Response in AML Using FLT PET/CT Imaging
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 20, 2016 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
57 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Diagnostic (anthracycline, cytarabine, FLT PET/CT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Other Intervention Name(s)
Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General
Intervention Description
Given anthracycline IV
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
Intervention Description
Undergo FLT PET/CT
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
.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
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Fluorothymidine F-18
Other Intervention Name(s)
18F-FLT, 3'-Deoxy-3'-(18F) Fluorothymidine, 3'-deoxy-3'-[18F]fluorothymidine, ALOVUDINE F-18, Fluorothymidine F 18
Intervention Description
Undergo FLT PET/CT
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT
Intervention Description
Undergo FLT PET/CT
Primary Outcome Measure Information:
Title
Negative predictive value of post-treatment FLT PET/CT imaging for CR in comparison with blast counts from bone marrow biopsy (BMBX)
Description
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).
Time Frame
Up to day 35
Secondary Outcome Measure Information:
Title
PPV of post-treatment FLT PET/CT imaging for complete remission
Description
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).
Time Frame
Up to day 35
Title
Sensitivity of FLT PET/CT for complete remission detection
Description
The binomial proportions and the corresponding Exact confidence intervals will be calculated for sensitivity estimation.
Time Frame
Up to day 35
Title
Specificity of FLT PET/CT for complete remission detection
Description
The binomial proportions and the corresponding Exact confidence intervals will be calculated for specificity estimation.
Time Frame
Up to day 35
Title
Pre-treatment FLT PET/CT activity as a predictor of complete remission
Description
The receiver operating characteristic (ROC) approach will be used to test the continue measurement of this variable in predicting CR.
Time Frame
Baseline
Title
Change between pre-treatment and post-treatment FLT PET/CT activity as a predictor of complete remission
Description
The ROC approach will be used to test the continue measurement of this variable in predicting CR.
Time Frame
Baseline to up to day 35
Title
Biologic correlates of AML (MRD assessment)
Description
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.
Time Frame
At day 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Jeraj
Organizational Affiliation
ECOG-ACRIN Cancer Research Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
UNC Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
University of Pennsylvania/Abramson Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
UT Southwestern/Simmons Cancer Center-Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Huntsman Cancer Institute/University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
University of Wisconsin Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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