Multi-Modality Imaging and Correlative Studies in Patients With Leukemia
Overview
- Phase
- Early Phase 1
- Intervention
- Biospecimen Collection
- Conditions
- Acute Lymphoblastic Leukemia
- Sponsor
- City of Hope Medical Center
- Enrollment
- 74
- Locations
- 1
- Primary Endpoint
- Hematopoietic stem cell density in bone marrow biopsy samples (sub-analysis)
- Status
- Recruiting
- Last Updated
- 17 days ago
Overview
Brief Summary
This clinical trial investigates multi-modality imaging and collection of biospecimen samples in understanding bone marrow changes in patients with acute myeloid leukemia undergoing total body irradiation (TBI) and chemotherapy. Using multi-modality imaging and collecting biospecimen samples may help doctors know more about how TBI and chemotherapy can change the bone marrow.
Detailed Description
PRIMARY OBJECTIVES: I. Temporal assessment of treatment impact on bone marrow. II. Relative assessment of bone marrow status between total marrow and lymphoid irradiation (TMLI) and conventional TBI. SECONDARY OBJECTIVES: I. Correlation of dual energy computed tomography (DECT), magnetic resonance imaging (MRI) imaging with biological samples for cellularity/adiposity. II. Feasibility of fluorothymidine F-18 (FLT) positron emission tomography (PET) imaging biomarker as a predictor of treatment response. III. Correlation of FLT PET imaging with biological correlate for leukemia. IV. Characterize relative distribution of leukemia in bone marrow (BM) environment. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT I (TLMI+FLT/TMLI): Patients may undergo optional fluorothymidine F-18 PET scan over 2 hours at baseline, on days 30 and 100, at 1 year, and at time of relapse. Patients undergo DECT and water-fat MRI scan over 30 minutes at baseline, on days 30 and 100, at year 1, and at time of relapse. Patients also undergo collection of bone marrow and blood samples at baseline, on days 30 and 100, and at 1 year. Patients undergo fluorothymidine F-18 PET, DECT, and water-fat MRI as in TMLI+FLT. COHORT II (TBI): Patients undergo collection of bone marrow at baseline, day 30, time of relapse, and at 1 year.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Cohort TMLI+FLT: AML patients eligible for and enrolling on COH 14012 or IRB 17505 that agree to participate in optional FLT PET imaging
- •Note: patients enrolling on IRB 19518 cannot enroll onto this cohort, but they may enroll on Cohort TMLI (below)
- •Cohort TMLI: AML or ALL patients eligible for and enrolling on COH 14012, IRB 17505 or IRB 19518
- •Cohort TBI: First or second remission AML or ALL patients that will receive TBI (13.2 Gy) plus chemotherapy (etoposide \[VP16\] 60 mg/kg or cyclophosphamide \[Cy\] 60 mg/kg for two days) as part of their standard of care
- •Cohort TBI: Documented written informed consent of participant
- •Cohort TBI: Age \>= 18 to =\< 60 years
- •Cohort TBI: Patients who have not received a prior transplant
Exclusion Criteria
- Not provided
Arms & Interventions
Cohort II (TBI)
Patients undergo collection of bone marrow at baseline, day 30, time of relapse, and at 1 year.
Intervention: Biospecimen Collection
Cohort I (TMLI+FLT/TMLI)
Patients may undergo optional fluorothymidine F-18 PET scan over 2 hours at baseline, on days 30 and 100, at 1 year, and at time of relapse. Patients undergo DECT and water-fat MRI scan over 30 minutes at baseline, on days 30 and 100, at year 1, and at time of relapse. Patients also undergo collection of bone marrow and blood samples at baseline, on days 30 and 100, and at 1 year. Patients undergo fluorothymidine F-18 PET, DECT, and water-fat MRI as in TMLI+FLT.
Intervention: Positron Emission Tomography
Cohort I (TMLI+FLT/TMLI)
Patients may undergo optional fluorothymidine F-18 PET scan over 2 hours at baseline, on days 30 and 100, at 1 year, and at time of relapse. Patients undergo DECT and water-fat MRI scan over 30 minutes at baseline, on days 30 and 100, at year 1, and at time of relapse. Patients also undergo collection of bone marrow and blood samples at baseline, on days 30 and 100, and at 1 year. Patients undergo fluorothymidine F-18 PET, DECT, and water-fat MRI as in TMLI+FLT.
Intervention: Magnetic Resonance Imaging
Cohort I (TMLI+FLT/TMLI)
Patients may undergo optional fluorothymidine F-18 PET scan over 2 hours at baseline, on days 30 and 100, at 1 year, and at time of relapse. Patients undergo DECT and water-fat MRI scan over 30 minutes at baseline, on days 30 and 100, at year 1, and at time of relapse. Patients also undergo collection of bone marrow and blood samples at baseline, on days 30 and 100, and at 1 year. Patients undergo fluorothymidine F-18 PET, DECT, and water-fat MRI as in TMLI+FLT.
Intervention: Biospecimen Collection
Cohort I (TMLI+FLT/TMLI)
Patients may undergo optional fluorothymidine F-18 PET scan over 2 hours at baseline, on days 30 and 100, at 1 year, and at time of relapse. Patients undergo DECT and water-fat MRI scan over 30 minutes at baseline, on days 30 and 100, at year 1, and at time of relapse. Patients also undergo collection of bone marrow and blood samples at baseline, on days 30 and 100, and at 1 year. Patients undergo fluorothymidine F-18 PET, DECT, and water-fat MRI as in TMLI+FLT.
Intervention: Laboratory Biomarker Analysis
Cohort II (TBI)
Patients undergo collection of bone marrow at baseline, day 30, time of relapse, and at 1 year.
Intervention: Laboratory Biomarker Analysis
Cohort I (TMLI+FLT/TMLI)
Patients may undergo optional fluorothymidine F-18 PET scan over 2 hours at baseline, on days 30 and 100, at 1 year, and at time of relapse. Patients undergo DECT and water-fat MRI scan over 30 minutes at baseline, on days 30 and 100, at year 1, and at time of relapse. Patients also undergo collection of bone marrow and blood samples at baseline, on days 30 and 100, and at 1 year. Patients undergo fluorothymidine F-18 PET, DECT, and water-fat MRI as in TMLI+FLT.
Intervention: Dual-Energy Computed Tomography
Cohort I (TMLI+FLT/TMLI)
Patients may undergo optional fluorothymidine F-18 PET scan over 2 hours at baseline, on days 30 and 100, at 1 year, and at time of relapse. Patients undergo DECT and water-fat MRI scan over 30 minutes at baseline, on days 30 and 100, at year 1, and at time of relapse. Patients also undergo collection of bone marrow and blood samples at baseline, on days 30 and 100, and at 1 year. Patients undergo fluorothymidine F-18 PET, DECT, and water-fat MRI as in TMLI+FLT.
Intervention: Fluorothymidine F-18
Outcomes
Primary Outcomes
Hematopoietic stem cell density in bone marrow biopsy samples (sub-analysis)
Time Frame: Up to 2 years
Will be assessed by CD34 staining.
Ratio of HSC sub-populations (sub-analysis)
Time Frame: Up to 2 years
Long-term, short-term, multi-potent progenitor, common myeloid progenitor, and granulocyte macrophage progenitor will all be assessed by HSCs marrow aspirate.
Microvascular density in bone marrow biopsy samples (sub-analysis)
Time Frame: Up to 2 years
Will be assessed by CD31 staining.
Change over time in cellularity and adiposity
Time Frame: Up to 1 year post-hematopoietic stem cell transplant (HCT)
A non-parametric smoothing plot will be produced in the first step to view changes in the trend. Measurements will be summarized by mean +/- standard deviation (SD) at each time point. Exploratory within subjects' correlation will be examined using Pearson correlation between adjacent time points. A random-effects model will also be used to investigate whether there is significant time trend. Will use a two-sample t-test for comparing bone marrow cellularity percentage at pre-HCT and 1-year post-HCT between the total marrow and lymphoid irradiation (TMLI) group and total body irradiation (TBI) group (all cohorts). A paired t-test will also be carried out to examine if there is significant difference in changes of cellularity between these two groups.
Change over time of red marrow (cellularity) and yellow marrow (adipocyte)
Time Frame: Up to 2 years
A non-parametric smoothing plot will be produced in the first step to view changes in the trend. Measurements will be summarized by mean +/- SD at each time point. Exploratory within subjects' correlation will be examined using Pearson correlation between adjacent time points. A random-effects model will also be used to investigate whether there is significant time trend. In addition, bone marrow/peripheral blood measurements will be correlated with survival outcome (relapse).
Number of hematopoietic stem cell (HSC) colony forming units (sub-analysis)
Time Frame: Up to 2 years
Will be assessed by HSCs from marrow aspirate.
Secondary Outcomes
- SUV distribution and presence of focal hot spot(Baseline)
- Change in FLT PET activity(Baseline up to 2 years)
- SUVmean at iliac crest, lumber spine, and femur(Up to 2 years)
- SUVmean at site of biopsy(At time of biopsy)
- Standardized uptake value (SUV) distribution at different skeletal sites(Baseline)
- SUVmax at site of biopsy(At time of biopsy)
- Blast counts(Up to 2 years)
- SUVmax at iliac crest, lumber spine, and femur(Up to 2 years)