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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 : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
City of Hope Medical Center

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
Acute Myeloid Leukemia Acute Myeloid Leukemia in Remission Other: Fluorothymidine F-18 Procedure: Positron Emission Tomography Procedure: Dual-Energy Computed Tomography Procedure: Magnetic Resonance Imaging Procedure: Biospecimen Collection Other: Laboratory Biomarker Analysis

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. Relative assessment of chimerism engraftment kinetics between TMLI and TBI. III. Relative assessment of circulating cytokines between TMLI and TBI. IV. Feasibility of fluorothymidine F-18 (FLT) positron emission tomography (PET) imaging biomarker as a predictor of treatment response.

V. Correlation of FLT PET imaging with biological correlate for leukemia. VI. Characterize relative distribution of leukemia in bone marrow (BM) environment.

OUTLINE: Patients are assigned to 1 of 3 cohorts.

COHORT I (TLMI+FLT): Patients may undergo optional fluorothymidine F-18 PET scan over 2 hours at baseline, and on days -1, 30, and 60. Patients undergo DECT and water-fat MRI scan over 30 minutes at baseline, on days -1, 30, 60, and 180, and at years 1 and 2. Patients also undergo collection of bone marrow and blood samples at baseline, on days -4, -1, 30, 60,100, and 180, and at years 1 and 2.

COHORT II (TMLI): Patients undergo fluorothymidine F-18 PET, DECT, water-fat MRI, and collection of bone marrow and blood samples as in Cohort I.

COHORT III (TBI): Patients undergo DECT and water-fat MRI scan over 30 minutes at baseline and 1 year. Patients undergo collection of bone marrow and blood samples at baseline, on days 30 and 100, and at 1 year.


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Study Type : Observational
Estimated Enrollment : 74 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Multi-modality Imaging and Correlative Studies in Patients With Leukemia
Actual Study Start Date : February 15, 2018
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : February 2023


Group/Cohort Intervention/treatment
Cohort I TMLI+FLT/TMLI
Patients may undergo optional fluorothymidine F-18 PET scan over 2 hours at baseline, and on days -1, 30, and 60. Patients undergo DECT and water-fat MRI scan over 30 minutes at baseline, on days -1, 30, 60, and 180, and at years 1 and 2. Patients also undergo collection of bone marrow and blood samples at baseline, on days -4, -1, 30, 60,100, and 180, and at years 1 and 2; Patients undergo fluorothymidine F-18 PET, DECT, water-fat MRI, and collection of bone marrow and blood samples as in TMLI+FLT
Other: Fluorothymidine F-18
Undergo FLT PET
Other Names:
  • 18F-FLT
  • 3'-deoxy-3'-(18F) fluorothymidine
  • fluorothymidine F 18

Procedure: Positron Emission Tomography
Undergo FLT PET
Other Names:
  • Medical Imaging
  • PET
  • PET Scan
  • positron emission tomography scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging

Procedure: Dual-Energy Computed Tomography
Undergo DECT
Other Name: DECT

Procedure: Magnetic Resonance Imaging
Undergo water-fat MRI
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging
  • Magnetic Resonance /Nuclear Magnetic Resonance
  • MRI
  • MRI scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging

Procedure: Biospecimen Collection
Undergo collection of bone marrow and blood samples

Other: Laboratory Biomarker Analysis
Correlative studies

Cohort TBI
Patients undergo DECT and water-fat MRI scan over 30 minutes at baseline and 1 year. Patients undergo collection of bone marrow and blood samples at baseline, on days 30 and 100, and at 1 year.
Procedure: Positron Emission Tomography
Undergo FLT PET
Other Names:
  • Medical Imaging
  • PET
  • PET Scan
  • positron emission tomography scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging

Procedure: Dual-Energy Computed Tomography
Undergo DECT
Other Name: DECT

Procedure: Magnetic Resonance Imaging
Undergo water-fat MRI
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging
  • Magnetic Resonance /Nuclear Magnetic Resonance
  • MRI
  • MRI scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging

Procedure: Biospecimen Collection
Undergo collection of bone marrow and blood samples

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. 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.

  2. 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.

  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. 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.

  2. 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.

  3. Change in serum cytokine levels [ Time Frame: Baseline up to 2 years ]
    Will be assessed by enzyme-linked immunosorbent assay.

  4. 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.

  5. 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.

  6. Change in fluorothymidine F-18 (FLT) positron emission tomography (PET) activity [ Time Frame: Baseline up to 2 years ]
  7. Treatment response [ Time Frame: Up to 2 years ]
    Treatment response is the primary outcome of the protocol, i.e., change in cellularity over time.

  8. 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.


  9. 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.


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

  11. 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.

  12. 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.


Biospecimen Retention:   Samples With DNA
Bone marrow, blood


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
AML patients who will undergo TMLI radiation or TBI with similar chemotherapy at City of Hope
Criteria

Inclusion Criteria:

  • Cohort TMLI+FLT: AML patients eligible for and enrolling on COH 14012 that agree to participate in option FLT PET imaging
  • Cohort TMLI: AML patients eligible for and enrolling on COH 14012
  • Cohort TBI: First or second remission AML 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
  • Cohort TBI: Patients free of any psychiatric, social or compliance issues that, in the treating physician opinion, will interfere with the completion of the transplant treatment and follow up

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


Contacts
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Contact: Jeffrey Wong, MD 626 256-4673 jwong@coh.org

Locations
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United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Jeffrey Wong, MD    626-256-4673    jwong@coh.org   
Principal Investigator: Jeffrey Wong, MD         
Sponsors and Collaborators
City of Hope Medical Center
Investigators
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Principal Investigator: Jeffrey Wong, MD City of Hope Medical Center

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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT03422731     History of Changes
Other Study ID Numbers: 17222
NCI-2017-01778 ( Registry Identifier: NCI CTRP )
First Posted: February 6, 2018    Key Record Dates
Last Update Posted: April 17, 2019
Last Verified: April 2019

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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
Neoplasms by Histologic Type
Neoplasms
Dideoxynucleosides
Alovudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents