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

Multi-Modality Imaging and Correlative Studies in Patients With Leukemia

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Procedure: Dual-Energy Computed Tomography; Procedure: Biospecimen Collection; Drug: Fluorothymidine F-18; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

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: Interventional
• Enrollment (Estimated): 74
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Medical Center
      • Principal Investigator: Jeffrey Y. Wong
      • Contact: Jeffrey Y. Wong; Phone Number: 626-218-2247; Email: jwong@coh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Dual-Energy Computed Tomography; Undergo DECT; Other Names: DECT; Procedure: Biospecimen Collection; Undergo collection of bone marrow and blood samples; Drug: Fluorothymidine F-18; Undergo FLT PET; Other Names: 18F-FLT; Fluorothymidine F 18; ALOVUDINE F-18; 3''-Deoxy-3''-(18F) Fluorothymidine; 3''-deoxy-3''-[18F]fluorothymidine; Procedure: Magnetic Resonance Imaging; Undergo water-fat MRI; Other Names: MRI; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR Imaging; 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
Active Comparator: Cohort II (TBI); Patients undergo collection of bone marrow at baseline, day 30, time of relapse, and at 1 year.	Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Biospecimen Collection; Undergo collection of bone marrow and blood samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change over time in cellularity and adiposity	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.	Up to 1 year post-hematopoietic stem cell transplant (HCT)
Change over time of red marrow (cellularity) and yellow marrow (adipocyte)	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).	Up to 2 years
Number of hematopoietic stem cell (HSC) colony forming units (sub-analysis)	Will be assessed by HSCs from marrow aspirate.	Up to 2 years
Ratio of HSC sub-populations (sub-analysis)	Long-term, short-term, multi-potent progenitor, common myeloid progenitor, and granulocyte macrophage progenitor will all be assessed by HSCs marrow aspirate.	Up to 2 years
Hematopoietic stem cell density in bone marrow biopsy samples (sub-analysis)	Will be assessed by CD34 staining.	Up to 2 years
Microvascular density in bone marrow biopsy samples (sub-analysis)	Will be assessed by CD31 staining.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standardized uptake value (SUV) distribution at different skeletal sites	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.	Baseline
SUV distribution and presence of focal hot spot	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.	Baseline
Change in FLT PET activity		Baseline up to 2 years
SUVmax at site 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 iliac crest. Image analysis is done at the different locations - iliac crest, Lumber spine, and femur.	At time of biopsy
SUVmean at site 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 iliac crest. Image analysis is done at the different locations - iliac crest, Lumber spine, and femur.	At time of biopsy
Blast counts	Will be assessed by bone marrow aspirate smears.	Up to 2 years
SUVmax at iliac crest, lumber spine, and femur	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.	Up to 2 years
SUVmean at iliac crest, lumber spine, and femur	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.	Up to 2 years

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jeffrey Y Wong, City of Hope Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2018
• Primary Completion (Estimated): November 6, 2024
• Study Completion (Estimated): November 6, 2024

Study Registration Dates

• First Submitted: October 2, 2017
• First Submitted That Met QC Criteria: January 30, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Estimated): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Anti-Infective Agents; Antiviral Agents; Alovudine
• Other Study ID Numbers: 17222 (Other Identifier: City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2017-01778 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• 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