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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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Procedure: Biospecimen Collection Procedure: Dual-Energy Computed Tomography Drug: Fluorothymidine F-18 Other: Laboratory Biomarker Analysis Procedure: Magnetic Resonance Imaging Procedure: Positron Emission Tomography Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Multi-Modality Imaging and Correlative Studies in Patients With Leukemia
Actual Study Start Date : February 6, 2018
Estimated Primary Completion Date : February 6, 2023
Estimated Study Completion Date : February 6, 2023

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Arms and Interventions
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Arm Intervention/treatment
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.
 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
Experimental: Cohort II (TBI)
Patients undergo collection of bone marrow at baseline, day 30, time of relapse, and at 1 year.
 Procedure: Biospecimen Collection
Undergo collection of bone marrow and blood samples

Other: Laboratory Biomarker Analysis
Correlative studies


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. Hematopoietic stem cell density in bone marrow biopsy samples (sub-analysis) [ Time Frame: Up to 2 years ]
    Will be assessed by CD34 staining.

  6. Microvascular density in bone marrow biopsy samples (sub-analysis) [ Time Frame: Up to 2 years ]
    Will be assessed by CD31 staining.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Change in FLT PET activity [ Time Frame: Baseline up to 2 years ]
  4. 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.


  5. 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.


  6. Blast counts [ Time Frame: Up to 2 years ]
    Will be assessed by bone marrow aspirate smears.

  7. 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.

  8. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03422731


Locations
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United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Jeffrey Y. Wong    626-218-2247    jwong@coh.org   
Principal Investigator: Jeffrey Y. Wong         
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jeffrey Y Wong City of Hope Medical Center
More Information
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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT03422731    
Other Study ID Numbers: 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 )
First Posted: February 6, 2018    Key Record Dates
Last Update Posted: December 8, 2020
Last Verified: May 2020

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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
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Alovudine
Antiviral Agents
Anti-Infective Agents