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

Phase 2

Active, not recruiting

• Conditions: Acute Myeloid Leukemia
• Interventions: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Chemotherapy; Procedure: Computed Tomography; Drug: Cytarabine; Other: Fluorothymidine F-18; Other: Laboratory Biomarker Analysis; Procedure: Positron Emission Tomography

• Registration Number: NCT02392429
• Lead Sponsor: National Cancer Institute (NCI)

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 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 Timeline

• Study First Submitted: 2015-03-18
• Study First Submitted QC: 2015-03-18
• Study First Posted: 2015-03-19
• Study Start: 2016-04-20
• Primary Completion: 2023-12-31
• Results First Submitted: 2024-03-28
• Results First Submitted QC: 2024-07-15
• Results First Posted: 2024-08-06
• Status Verified: 2024-09
• Last Update Submitted: 2024-10-16
• Last Update Posted: 2024-10-17
• Study Completion: 2025-02-13

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 87

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)

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic (anthracycline, cytarabine, FLT PET/CT)	Biospecimen Collection	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.
Diagnostic (anthracycline, cytarabine, FLT PET/CT)	Bone Marrow Aspiration	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.
Diagnostic (anthracycline, cytarabine, FLT PET/CT)	Bone Marrow Biopsy	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.
Diagnostic (anthracycline, cytarabine, FLT PET/CT)	Chemotherapy	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.
Diagnostic (anthracycline, cytarabine, FLT PET/CT)	Computed Tomography	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.
Diagnostic (anthracycline, cytarabine, FLT PET/CT)	Laboratory Biomarker Analysis	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.
Diagnostic (anthracycline, cytarabine, FLT PET/CT)	Positron Emission Tomography	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.
Diagnostic (anthracycline, cytarabine, FLT PET/CT)	Fluorothymidine F-18	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.
Diagnostic (anthracycline, cytarabine, FLT PET/CT)	Cytarabine	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.

Primary Outcome Measures

Name	Time	Method
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)	Up to day 35	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 )

Secondary Outcome Measures

Name	Time	Method
Positive Predictive Value (PPV) of Post-treatment FLT PET/CT Imaging for Complete Remission	Up to day 35	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 Post-treatment FLT PET/CT for Detecting Complete Remission (a Clinical Response of CR, CRi, or LFS )	Up to day 35	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
Specificity of Post-treatment FLT PET/CT for Detecting Complete Remission	Up to day 35	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
FLT PET/CT Imaging Parameters With Biologic Correlates (Minimal Residual Disease Assessment)	Up to day 35	FLT PET/CT imaging features will be compared with biologic correlates (minimal residual disease \[MRD\] assessment).
FLT PET/CT Imaging to Predict Relapse-free Survival	Up to day 35 and up to 4 years for RFS	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.
FLT PET/CT Imaging to Predict Overall Survival	Up to day 35 and up to 4 years for RFS	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.

Trial Locations

Locations (11)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Mount Sinai Hospital; 🇺🇸 New York, New York, United States

UNC Lineberger Comprehensive Cancer Center; 🇺🇸 Chapel Hill, North Carolina, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

University of Pennsylvania/Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Vanderbilt University/Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

UT Southwestern/Simmons Cancer Center-Dallas; 🇺🇸 Dallas, Texas, United States

Huntsman Cancer Institute/University of Utah; 🇺🇸 Salt Lake City, Utah, United States

University of Wisconsin Carbone Cancer Center - University Hospital; 🇺🇸 Madison, Wisconsin, United States