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.
Active, not recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Chemotherapy | Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General | Diagnostic (anthracycline, cytarabine, FLT PET/CT) |
| Cytarabine | .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 | Diagnostic (anthracycline, cytarabine, FLT PET/CT) |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Diagnostic (anthracycline, cytarabine, FLT PET/CT) | Experimental | 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. |
|
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)
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Negative predictive value of post-treatment FLT PET/CT imaging for CR in comparison with blast counts from bone marrow biopsy (BMBX) |
| Time Frame: | Up to day 35 |
| Safety Issue: | |
| 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). |
| Measure: | PPV of post-treatment FLT PET/CT imaging for complete remission |
| Time Frame: | Up to day 35 |
| Safety Issue: | |
| 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). |
| Measure: | Sensitivity of FLT PET/CT for complete remission detection |
| Time Frame: | Up to day 35 |
| Safety Issue: | |
| Description: | The binomial proportions and the corresponding Exact confidence intervals will be calculated for sensitivity estimation. |
| Measure: | Specificity of FLT PET/CT for complete remission detection |
| Time Frame: | Up to day 35 |
| Safety Issue: | |
| Description: | The binomial proportions and the corresponding Exact confidence intervals will be calculated for specificity estimation. |
| Measure: | Pre-treatment FLT PET/CT activity as a predictor of complete remission |
| Time Frame: | Baseline |
| Safety Issue: | |
| Description: | The receiver operating characteristic (ROC) approach will be used to test the continue measurement of this variable in predicting CR. |
| Measure: | Change between pre-treatment and post-treatment FLT PET/CT activity as a predictor of complete remission |
| Time Frame: | Baseline to up to day 35 |
| Safety Issue: | |
| Description: | The ROC approach will be used to test the continue measurement of this variable in predicting CR. |
| Measure: | Biologic correlates of AML (MRD assessment) |
| Time Frame: | At day 14 |
| Safety Issue: | |
| 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. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | National Cancer Institute (NCI) |
August 4, 2021
