Imaging and Biospecimen Collection for Acute Myeloid Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: City of Hope Medical Center

Disqualifiers: Prior transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 30

Duration: Up to 1 year

74 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how treatments like total body irradiation (TBI) and chemotherapy affect bone marrow in patients with acute myeloid leukemia (AML). Researchers use advanced imaging techniques, including Dual-Energy Computed Tomography (DECT) and Magnetic Resonance Imaging (MRI), and collect samples to better understand these changes. The study includes two groups: one using a combination of imaging methods and another focusing on TBI and chemotherapy. This trial suits patients with AML or acute lymphoblastic leukemia (ALL) who have not had a transplant and are in their first or second remission, receiving TBI and chemotherapy as part of their standard care. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this imaging and biospecimen collection is safe for patients with acute myeloid leukemia?

A previous study showed that fluorothymidine F-18 (FLT) is safe for humans. It successfully passed at least one human trial and received approval for imaging in three different areas, indicating it is generally well-tolerated with no major safety concerns reported.

Dual-energy computed tomography (DECT) is a commonly used imaging method. It provides detailed images of the body and is generally considered safe, with research noting no specific adverse effects.

Magnetic resonance imaging (MRI) is also widely used in medical settings. Studies have shown it is a safe and reliable way to obtain detailed images of the body, including the bone marrow. No specific safety issues have been reported for MRI when used for imaging in acute myeloid leukemia.

Overall, these imaging methods—FLT, DECT, and MRI—have a history of safe use in humans, suggesting they are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to enhance the understanding of acute myeloid leukemia (AML) through advanced imaging and biospecimen collection techniques. Unlike traditional methods, such as standard chemotherapy and bone marrow transplants, this study explores the use of dual-energy computed tomography (DECT), fluorothymidine F-18 PET scans, and water-fat MRI to assess and monitor the disease more precisely over time. These innovative imaging approaches, combined with comprehensive collection of bone marrow and blood samples, could lead to earlier detection of relapse and a deeper understanding of the disease's progression, potentially improving treatment strategies and outcomes for patients with AML.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research has shown that certain imaging tests can track treatment effectiveness for patients with acute myeloid leukemia (AML). In this trial, participants in Cohort I will undergo fluorothymidine F-18 PET scans, which highlight changes in the bone marrow, indicating the disease's response to treatment. Dual-energy computed tomography (DECT) will also be used in Cohort I to reveal differences in bone marrow throughout the body, helping doctors identify where leukemia is most active. Magnetic resonance imaging (MRI) will provide clear images of bone marrow changes, aiding in diagnosing and monitoring the disease. Together, these imaging techniques offer a detailed view of disease progression and treatment response. ^{1 2 3 6 7}

Who Is on the Research Team?

Jeffrey Wong

Principal Investigator

City of Hope Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), who are in their first or second remission and haven't had a prior transplant. They must be eligible for certain other studies, consent to participate, and agree to undergo specific imaging if enrolling on COH 14012 or IRB 17505.

Inclusion Criteria

I have never had a transplant before.

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, IRB 17505 or IRB 19518

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo total body irradiation (TBI) and chemotherapy, with imaging and biospecimen collection

Up to 1 year

Baseline, day 30, day 100, 1 year, and at time of relapse

Follow-up

Participants are monitored for changes in bone marrow cellularity and adiposity, and other secondary outcomes

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Biospecimen Collection
• Dual-Energy Computed Tomography
• Fluorothymidine F-18
• Magnetic Resonance Imaging

Trial Overview The study is examining how total body irradiation (TBI) combined with chemotherapy affects bone marrow changes in AML/ALL patients. It involves advanced imaging techniques like Dual-Energy CT, MRI, PET scans using Fluorothymidine F-18, and collecting biospecimen samples.

How Is the Trial Designed?

Group I: Cohort I (TMLI+FLT/TMLI) Experimental Treatment 6 Interventions

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.

Group II: Cohort II (TBI) Active Control 2 Interventions

Patients undergo collection of bone marrow at baseline, day 30, time of relapse, and at 1 year.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Magnetic resonance imaging (MRI) can non-invasively monitor bone marrow conditions, showing elevated T1 relaxation times in patients with acute myelogenous leukemia (AML).

While interpatient variability limits its diagnostic use, tracking T1 relaxation times over time can provide early and sensitive indications of leukemic relapse, potentially reducing the need for frequent bone marrow aspirates and biopsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging for monitoring relapse of acute myeloid leukemia. Henkelman, RM., Messner, H., Poon, PY., et al.[2019]

F-Fluorothymidine-positron emission tomography with CT fusion ([F]FLT-PET/CT) is a non-invasive imaging technique that effectively localizes and quantifies functional bone marrow, which is crucial for planning radiotherapy in patients at risk of marrow toxicity.

In a case of a patient with chemo-refractory lymphoma, [F]FLT-PET/CT was instrumental in identifying functional bone marrow distribution, aiding in 'marrow-sparing' radiotherapy planning, and assessing the impact of radiotherapy on bone marrow health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Application of [18F]Fluorothymidine-PET ([18F]FLT-PET) in Clinical Practice to Quantify Regional Bone Marrow Function in a Patient With Treatment-Induced Cytopenias and to Guide "Marrow-Sparing" Radiotherapy. Campbell, BA., Hofman, MS., Prince, HM.[2019]

The study found a strong correlation between changes in [(18)F]FLT uptake in PET scans and the radiation dose received by bone marrow in 10 head and neck cancer patients, indicating that PET imaging can effectively monitor bone marrow response to radiation treatment.

Significant reductions in [(18)F]FLT uptake were observed at doses greater than 6 Gy/week, suggesting a potential threshold for minimizing bone marrow toxicity during chemoradiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3'-deoxy-3'-[¹⁸F]fluorothymidine PET quantification of bone marrow response to radiation dose. McGuire, SM., Menda, Y., Boles Ponto, LL., et al.[2021]

Dual-energy computed tomography (DECT) provides enhanced imaging of the spine by effectively removing bone and iodinated contrast, which improves the clarity of images.

This technique has promising new applications, including the ability to noninvasively assess conditions like spinal gout and improve bone density measurements, making it valuable for diagnosing acute trauma and myeloinfiltrative disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual Energy Computed Tomography Applications for the Evaluation of the Spine. Komlosi, P., Wintermark, M.[2018]

A new imaging method combining FLT-PET and DECT effectively identifies the distribution of leukemia within both red and yellow bone marrow, revealing that leukemia adheres to cortical bone and is more active in certain areas like the femur.

Using this imaging approach for functional total marrow irradiation (fTMI) allows for targeted radiation treatment that significantly increases the dose to active leukemia while keeping doses to critical organs similar to conventional treatments, potentially improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole-Body Distribution of Leukemia and Functional Total Marrow Irradiation Based on FLT-PET and Dual-Energy CT. Magome, T., Froelich, J., Holtan, SG., et al.[2018]

This research project aims to evaluate the effectiveness of FLT-PET imaging in diagnosing and monitoring treatment responses in patients with primary myelofibrosis (PMF) and Essential Thrombocythemia (ET), focusing on its uptake patterns.

The study will also compare FLT-PET imaging results with traditional bone marrow biopsies and explore the relationship between FLT-PET uptake and specific genetic mutations, such as JAK2 and CALR, in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study of 18F-FLT positron emission tomography/computed tomography imaging in cases of prefibrotic/early primary myelofibrosis and essential thrombocythemia. Yassin, MA., Nehmeh, SA., Nashwan, AJ., et al.[2022]

In a study of 50 lung cancer patients undergoing platinum-doublet chemotherapy, low accumulation of 18F-FLT in the L4 vertebral body was identified as a strong predictor of severe hematological toxicities, with a sensitivity of 80% and specificity of 86.7%.

The findings suggest that 18F-FLT PET imaging can help estimate the risk of severe hematological toxicities, potentially guiding treatment decisions regarding drug combinations and dosage for patients with advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The vertebral 3'-deoxy-3'-18F-fluorothymidine uptake predicts the hematological toxicity after systemic chemotherapy in patients with lung cancer. Umeda, Y., Tsujikawa, T., Anzai, M., et al.[2021]

In a study involving 18 cancer patients and 1105 bones, the use of dual-energy computed-tomography bone marrow color maps significantly improved the sensitivity of detecting bone metastases, increasing from 76.2% to 86.8% for one radiologist and from 80.2% to 92.8% for another.

The analysis not only enhanced sensitivity but also improved specificity and accuracy in detecting metastatic lesions, indicating that this imaging technique can lead to more reliable diagnoses in patients with metastatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ability of Dual-Energy Computed Tomography to Distinguish Normal Bone Marrow From Metastases Using Bone Marrow Color Maps. Issa, G., Davis, D., Mulligan, ME.[2018]

In a study of 10 adult patients with acute myeloid leukemia (AML) who underwent 18F-FLT PET/CT after induction therapy, the imaging technique effectively distinguished between patients with resistant disease and those in remission, showing good sensitivity and negative-predictive value.

The results indicated that 18F-FLT PET/CT could serve as a valuable noninvasive tool for early treatment response assessment and may help predict clinical outcomes, as PET-positive patients were more likely to experience relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early assessment of response to induction therapy in acute myeloid leukemia using 18F-FLT PET/CT. Han, EJ., Lee, BH., Kim, JA., et al.[2020]

In a study of 10 patients with recurrent glioblastoma multiforme, FLT-PET imaging showed significant uptake in tumors, indicating its potential usefulness for detecting tumor recurrence.

While there was a strong correlation between FLT uptake and Gd-DTPA enhancement in MRI, the differences in their areas suggest that FLT-PET may not directly correlate with Gd-DTPA enhancement, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3'-Deoxy-3'-[F-18]fluorothymidine positron emission tomography in patients with recurrent glioblastoma multiforme: comparison with Gd-DTPA enhanced magnetic resonance imaging. Yamamoto, Y., Wong, TZ., Turkington, TG., et al.[2022]

In a pilot study involving 10 patients with acute myeloid leukemia (AML), the imaging technique using 18F-fluorothymidine (FLT) PET was effective in visualizing sites of leukemia, particularly showing higher retention in bone marrow and spleen compared to controls.

The study found that 18F-FLT PET could identify extramedullary manifestations of AML in 4 patients, indicating its potential as a surrogate marker for disease activity, although the correlation with leukemic blast infiltration in bone marrow was not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First demonstration of leukemia imaging with the proliferation marker 18F-fluorodeoxythymidine. Buck, AK., Bommer, M., Juweid, ME., et al.[2016]

Dual energy CT (DECT) imaging is validated as an effective biomarker for measuring marrow fat (MF) and bone mineral density (BMD) in cancer survivors, showing a strong correlation with other imaging methods like water-fat MRI and quantitative CT.

After cancer treatment, there is a significant increase in marrow fat, particularly following chemotherapy and radiation, while bone mineral density decreases, indicating that MF and BMD should not be used interchangeably to assess skeletal health post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients. Hui, SK., Arentsen, L., Sueblinvong, T., et al.[2019]

Dual-energy CT (DECT) imaging enhances the identification of material characteristics compared to conventional single-energy CT, improving the visualization of hypervascular lesions and tissue contrast, which is crucial in oncology.

DECT allows for reduced iodinated contrast material usage, making it safer for patients with renal impairment and eliminating the need for precontrast scans, thus lowering overall radiation exposure during CT examinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual Energy CT in Oncology: Benefits for Both Patients and Radiologists From an Emerging Quantitative and Functional Diagnostic Technique. Guerrini, S., Bagnacci, G., Perrella, A., et al.[2023]

Dual-energy computed tomography (DECT) enhances oncological imaging by improving tumor detection and tissue characterization while reducing radiation exposure, making it a safer option for patients.

DECT's ability to provide fast, quantitative imaging and monitor therapy effectiveness highlights its growing importance in oncology, although its full potential is still being explored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent developments of dual-energy CT in oncology. Simons, D., Kachelriess, M., Schlemmer, HP.[2022]

Citations

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Whole-Body Distribution of Leukemia and Functional Total ... We recently reported on the use of WB dual-energy computed tomography (DECT) to reveal a skeletal-wide heterogeneity within red marrow (RM) and ...

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Functional imaging with dual-energy computed ... (B) Dual-energy CT revealed elevated virtual-non-calcium values with diffuse edema of the bone marrow. The high bone marrow mast cell ...

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Dual-Energy CT in Oncologic Imaging - PMC This technology allows for the simultaneous acquisition of data at different energy levels, typically high and low kilovoltage (kV), enabling the production of ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0899707122001243

Feasibility of half the recommended dose of IV contrast in ... DECT with 50% reduction in the volume of intravenous contrast produces image quality comparable to that of SECT in cancer patients.

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Figure 3. Comparison of conventional TMI, FLT-based ... This report describes a multimodal whole-body 3′-deoxy-3′[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography ( ...

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Acute Myeloid Leukemia A CT or CAT (computed tomography) scan uses x-rays and computer technology to take pictures of the inside of the body. It takes many x-rays of ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024109826

Targeted therapy for leukemia based on nanomaterials This paper gives an overview of the current therapeutic strategies for leukemia, and then reviews the cutting-edge targeted therapeutic nanomaterials for ...