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Multi-modality Imaging and Collection of Biospecimen Samples in Understanding Bone Marrow Changes in Patients With Acute Myeloid Leukemia Undergoing TBI and Chemotherapy

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ClinicalTrials.gov Identifier: NCT03422731
Recruitment Status : Recruiting
First Posted : February 6, 2018
Last Update Posted : December 8, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Tracking Information
First Submitted Date  ICMJE October 2, 2017
First Posted Date  ICMJE February 6, 2018
Last Update Posted Date December 8, 2020
Actual Study Start Date  ICMJE February 6, 2018
Estimated Primary Completion Date February 6, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 15, 2019)
  • 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.
  • 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.
  • Hematopoietic stem cell density in bone marrow biopsy samples (sub-analysis) [ Time Frame: Up to 2 years ]
    Will be assessed by CD34 staining.
  • Microvascular density in bone marrow biopsy samples (sub-analysis) [ Time Frame: Up to 2 years ]
    Will be assessed by CD31 staining.
Original Primary Outcome Measures  ICMJE
 (submitted: January 30, 2018)
  • Change over time in cellularity and adiposity [ Time Frame: Up to 1 year post-hematopoietic stem cell transplant (HCT) ]
    Will be assessed by bone marrow trephine hematoxylin and eosin (H&E) stain. Cellularity is the same as percent of red marrow and adipocyte is the same as percent of yellow marrow. The primary outcome is the change in cellularity (the percent of red marrow and it is unitless), which will be measured on days -1, 30, 60, and 180, and at years 1 and 2 for TMLI+FLT/TMLI group. And adipocyte is 1-cellularity. Patients in TBI group undergo collection of bone marrow and blood samples at baseline, on days 30 and 100, and at 1 year.
  • Change over time of red marrow (cellularity) and yellow marrow (adipocyte) [ Time Frame: Up to 2 years ]
    Will be assessed by water-fat magnetic resonance imaging (MRI) and dual energy computed tomography (DECT). Cellularity is the same as percent of red marrow and adipocyte is the same as percent of yellow marrow. The primary outcome is the change in cellularity (the percent of red marrow and it is unitless), which will be measured on days -1, 30, 60, and 180, and at years 1 and 2 for TMLI+FLT/TMLI group. And adipocyte is 1-cellularity. Patients in TBI group undergo collection of bone marrow and blood samples at baseline, on days 30 and 100, and at 1 year.
  • 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.
  • 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.
  • Hematopoietic stem cell density in bone marrow biopsy samples (sub-analysis) [ Time Frame: Up to 2 years ]
    Will be assessed by CD34 staining.
  • Microvascular density in bone marrow biopsy samples (sub-analysis) [ Time Frame: Up to 2 years ]
    Will be assessed by CD31 staining.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2019)
  • Standardized uptake value (SUV) distribution at different skeletal sites [ Time Frame: Baseline ]
    Changes in standardized uptake value (SUV) from fluorothymidine F-18 (FLT) positron emission tomography (PET) imaging uptake will be described. The distribution or heterogeneity will be first estimated using medians, ranges, interquartile ranges, means and standard deviations. Kolmogorov-Smirnov test (K-S) test will be performed to examine whether the distribution is the same for different skeletal sites. Also as a side product, sensitivity and specificity of the imaging will be estimated.
  • SUV distribution and presence of focal hot spot [ Time Frame: Baseline ]
    Changes in SUV from FLT-PET imaging uptake will be described. The distribution or heterogeneity will be first estimated using medians, ranges, interquartile ranges, means and standard deviations. K-S test will be performed to examine whether the distribution is the same for different skeletal sites. Also as a side product, sensitivity and specificity of the imaging will be estimated.
  • Change in FLT PET activity [ Time Frame: Baseline up to 2 years ]
  • SUVmax at site of biopsy [ Time Frame: At time of biopsy ]
    SUVmax: the maximum SUV within the region of interest. SUVmin: the minimum SUV within the region of interest. SUVmean: the average SUV within the region of interest. As a primary goal we will be using SUVmax. Other parameters are secondary parameters. Sites: site of bone marrow biopsy is Illiac crest. Image analysis is done at the different locations - iliac crest, Lumber spine, and femur.
  • SUVmean at site of biopsy [ Time Frame: At time of biopsy ]
    SUVmax: the maximum SUV within the region of interest. SUVmin: the minimum SUV within the region of interest. SUVmean: the average SUV within the region of interest. As a primary goal we will be using SUVmax. Other parameters are secondary parameters. Sites: site of bone marrow biopsy is Illiac crest. Image analysis is done at the different locations - iliac crest, Lumber spine, and femur.
  • Blast counts [ Time Frame: Up to 2 years ]
    Will be assessed by bone marrow aspirate smears.
  • SUVmax at iliac crest, lumber spine, and femur [ Time Frame: Up to 2 years ]
    For each location SUV measurement, software provides SUVmax, SUVmin and SUVmean. These are not separate measurements. Once region (volume) is defined, software will calculate SUV in the form of SUVmax, SUVmean and SUVmin. For simplicity, we will report SUVmax only as primary parameter. SUVmean and SUVmin will be secondary SUV parameters.
  • SUVmean at iliac crest, lumber spine, and femur [ Time Frame: Up to 2 years ]
    For each location SUV measurement, software provides SUVmax, SUVmin and SUVmean. These are not separate measurements. Once region (volume) is defined, software will calculate SUV in the form of SUVmax, SUVmean and SUVmin. For simplicity, we will report SUVmax only as primary parameter. SUVmean and SUVmin will be secondary SUV parameters.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2018)
  • Ratio of circulating donor cells for all nucleated cells and lineage specific cells [ Time Frame: Up to 30 days post-HCT ]
    Will assess CD3, CD19, CD33, and CD56.
  • Ratio of circulating host cells for all nucleated cells and lineage specific cells [ Time Frame: Up to 30 days post-HCT ]
    Will assess CD3, CD19, CD33, and CD56.
  • Change in serum cytokine levels [ Time Frame: Baseline up to 2 years ]
    Will be assessed by enzyme-linked immunosorbent assay.
  • Standardized uptake value (SUV) distribution at different skeletal times [ Time Frame: Baseline ]
    Standardized uptake value (SUV) is defined as a ratio of tissue radioactivity concentration at one particular time point and the injected dose of radioactivity per kilogram of the patient's body weight. The measure varies both in time and in site. Based on the definition, it is unitless. In each region of interest, SUVmax, SUVmin and SUVmean will be defined. SUV distribution is a "SUV" variation inter and intra-skeletal system.
  • SUV distribution and presence of focal hot spot [ Time Frame: Baseline ]
    Standardized uptake value (SUV) is defined as a ratio of tissue radioactivity concentration at one particular time point and the injected dose of radioactivity per kilogram of the patient's body weight. The measure varies both in time and in site. Based on the definition, it is unitless. In each region of interest, SUVmax, SUVmin and SUVmean will be defined. SUV distribution is a "SUV" variation inter and intra-skeletal system.
  • Change in fluorothymidine F-18 (FLT) positron emission tomography (PET) activity [ Time Frame: Baseline up to 2 years ]
  • Treatment response [ Time Frame: Up to 2 years ]
    Treatment response is the primary outcome of the protocol, i.e., change in cellularity over time.
  • SUVmax at site of biopsy [ Time Frame: At time of biopsy ]
    SUVmax: the maximum SUV within the region of interest. SUVmin: the minimum SUV within the region of interest. SUVmean: the average SUV within the region of interest. As a primary goal we will be using SUVmax. Other parameters are secondary parameters. Sites: site of bone marrow biopsy is Illiac crest. Image analysis is done at the different locations - iliac crest, Lumber spine, and femur.
  • SUVmean at site of biopsy [ Time Frame: At time of biopsy ]
    SUVmax: the maximum SUV within the region of interest. SUVmin: the minimum SUV within the region of interest. SUVmean: the average SUV within the region of interest. As a primary goal we will be using SUVmax. Other parameters are secondary parameters. Sites: site of bone marrow biopsy is Illiac crest. Image analysis is done at the different locations - iliac crest, Lumber spine, and femur.
  • Blast counts [ Time Frame: Up to 2 years ]
    Will be assessed by bone marrow aspirate smears.
  • SUVmax at iliac crest, lumber spine, and femur [ Time Frame: Up to 2 years ]
    For each location SUV measurement, software provides SUVmax, SUVmin and SUVmean. These are not separate measurements. Once region (volume) is defined, software will calculate SUV in the form of SUVmax, SUVmean and SUVmin. For simplicity, we will report SUVmax only as primary parameter. SUVmean and SUVmin will be secondary SUV parameters.
  • SUVmean at iliac crest, lumber spine, and femur [ Time Frame: Up to 2 years ]
    For each location SUV measurement, software provides SUVmax, SUVmin and SUVmean. These are not separate measurements. Once region (volume) is defined, software will calculate SUV in the form of SUVmax, SUVmean and SUVmin. For simplicity, we will report SUVmax only as primary parameter. SUVmean and SUVmin will be secondary SUV parameters.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Multi-modality Imaging and Collection of Biospecimen Samples in Understanding Bone Marrow Changes in Patients With Acute Myeloid Leukemia Undergoing TBI and Chemotherapy
Official Title  ICMJE Multi-Modality Imaging and Correlative Studies in Patients With Leukemia
Brief Summary This pilot clinical trial studies 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 mutli-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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
Intervention  ICMJE
  • Procedure: Biospecimen Collection
    Undergo collection of bone marrow and blood samples
  • Procedure: Dual-Energy Computed Tomography
    Undergo DECT
    Other Name: DECT
  • Drug: Fluorothymidine F-18
    Undergo FLT PET
    Other Names:
    • 18F-FLT
    • 3''-Deoxy-3''-(18F) Fluorothymidine
    • 3''-deoxy-3''-[18F]fluorothymidine
    • ALOVUDINE F-18
    • Fluorothymidine F 18
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Procedure: Magnetic Resonance Imaging
    Undergo water-fat MRI
    Other Names:
    • Magnetic Resonance Imaging Scan
    • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
    • MR Imaging
    • MRI
    • MRI Scan
    • NMR Imaging
    • NMRI
    • Nuclear Magnetic Resonance Imaging
  • Procedure: Positron Emission Tomography
    Undergo FLT PET
    Other Names:
    • Medical Imaging, Positron Emission Tomography
    • PET
    • PET Scan
    • Positron Emission Tomography Scan
    • Positron-Emission Tomography
    • proton magnetic resonance spectroscopic imaging
Study Arms  ICMJE
  • Experimental: Cohort I (TMLI+FLT/TMLI)
    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.
    Interventions:
    • Procedure: Biospecimen Collection
    • Procedure: Dual-Energy Computed Tomography
    • Drug: Fluorothymidine F-18
    • Other: Laboratory Biomarker Analysis
    • Procedure: Magnetic Resonance Imaging
    • Procedure: Positron Emission Tomography
  • Experimental: Cohort II (TBI)
    Patients undergo collection of bone marrow at baseline, day 30, time of relapse, and at 1 year.
    Interventions:
    • Procedure: Biospecimen Collection
    • Other: Laboratory Biomarker Analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 30, 2018)
74
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 6, 2023
Estimated Primary Completion Date February 6, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Cohort TMLI: AML or ALL patients eligible for and enrolling on COH 14012 or IRB 17505
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03422731
Other Study ID Numbers  ICMJE 17222
NCI-2017-01778 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
17222 ( Other Identifier: City of Hope Comprehensive Cancer Center )
P30CA033572 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party City of Hope Medical Center
Study Sponsor  ICMJE City of Hope Medical Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Jeffrey Y Wong City of Hope Medical Center
PRS Account City of Hope Medical Center
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP