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.
Brief Title
FLT PET/CT in Measuring Response in Patients With Previously Untreated Acute Myeloid Leukemia
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.
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Acute Myeloid Leukemia
Eligibility Criteria
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)
* 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)
Inclusion Criteria
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)
* 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)
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02392429
Org Class
Nih
Org Full Name
National Cancer Institute (NCI)
Org Study Id
NCI-2015-00328
Overall Status
Active, not recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Early Assessment of Treatment Response in AML Using FLT PET/CT Imaging
Primary Outcomes
Outcome Description
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 )
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 )
Outcome Measure
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)
Outcome Time Frame
Up to day 35
Secondary Ids
Secondary Id
NCI-2015-00328
Secondary Id
EAI141
Secondary Id
EAI141
Secondary Id
EAI141
Secondary Id
U10CA180820
Secondary Id
U10CA180827
Secondary Outcomes
Outcome 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).
Outcome Time Frame
Up to day 35
Outcome Measure
Positive Predictive Value (PPV) of Post-treatment FLT PET/CT Imaging for Complete Remission
Outcome Description
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
FLT Test :
Negative: SUV \>7; Positive: SUV\<=7
Clinical Response:
Negative: not (CR, CRi, or LFS); Positive (Responders): CR, CRi, or LFS
Outcome Time Frame
Up to day 35
Outcome Measure
Sensitivity of Post-treatment FLT PET/CT for Detecting Complete Remission (a Clinical Response of CR, CRi, or LFS )
Outcome Description
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
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
Outcome Time Frame
Up to day 35
Outcome Measure
Specificity of Post-treatment FLT PET/CT for Detecting Complete Remission
Outcome Description
FLT PET/CT imaging features will be compared with biologic correlates (minimal residual disease \[MRD\] assessment).
Outcome Time Frame
Up to day 35
Outcome Measure
FLT PET/CT Imaging Parameters With Biologic Correlates (Minimal Residual Disease Assessment)
Outcome Description
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.
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.
Outcome Time Frame
Up to day 35 and up to 4 years for RFS
Outcome Measure
FLT PET/CT Imaging to Predict Relapse-free Survival
Outcome Description
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.
Participants were followed for survival outcomes until study closure when the last participant has been followed for 1 year after study enrollment.
Outcome Time Frame
Up to day 35 and up to 4 years for RFS
Outcome Measure
FLT PET/CT Imaging to Predict Overall Survival
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Aditi Shastri
Investigator Email
ASHASTRI@montefiore.org
Investigator Phone
718-920-4826
Categories Mesh Debug
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID, ACUTE
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Cancer --- NEOPLASMS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
MeSH Terms
LEUKEMIA, MYELOID, ACUTE
LEUKEMIA, MYELOID
LEUKEMIA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
SPECIMEN HANDLING
BIOPSY
DRUG THERAPY
CYTARABINE
ALOVUDINE
MAGNETIC RESONANCE SPECTROSCOPY
CLINICAL LABORATORY TECHNIQUES
DIAGNOSTIC TECHNIQUES AND PROCEDURES
DIAGNOSIS
INVESTIGATIVE TECHNIQUES
CYTODIAGNOSIS
CYTOLOGICAL TECHNIQUES
DIAGNOSTIC TECHNIQUES, SURGICAL
SURGICAL PROCEDURES, OPERATIVE
THERAPEUTICS
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
ARABINONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES
SPECTRUM ANALYSIS
CHEMISTRY TECHNIQUES, ANALYTICAL