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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the treatment involving Dual-Energy Computed Tomography (DECT) for Acute Myeloid Leukemia?

Research shows that Dual-Energy Computed Tomography (DECT) is beneficial in cancer imaging by improving tumor detection and characterization, reducing radiation dose, and enhancing tissue contrast, which can help monitor changes during treatment. ^{1 2 3 4 5}

Is the imaging and biospecimen collection method for acute myeloid leukemia safe for humans?

The studies involving Fluorothymidine F-18 (FLT) and Dual-Energy CT (DECT) suggest that these imaging methods are generally safe for humans, as they have been used to assess bone marrow function and guide radiation therapy without significant safety concerns reported. ^{6 7 8 9 10}

How does this treatment for acute myeloid leukemia differ from other treatments?

This treatment uses advanced imaging techniques like 18F-FLT PET/CT to visualize and assess the distribution of leukemia in the body, which helps in planning targeted radiation strategies. This approach is unique because it allows for more precise targeting of leukemia cells while sparing healthy tissue, potentially improving treatment outcomes. ^{6 11 12 13 14}

Research Team

Jeffrey Wong

Principal Investigator

City of Hope Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Dual Energy Computed Tomography Applications for the Evaluation of the Spine. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Recent developments of dual-energy CT in oncology. [2022]

3. United States 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. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Dual Energy CT in Oncology: Benefits for Both Patients and Radiologists From an Emerging Quantitative and Functional Diagnostic Technique. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

The Ability of Dual-Energy Computed Tomography to Distinguish Normal Bone Marrow From Metastases Using Bone Marrow Color Maps. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Whole-Body Distribution of Leukemia and Functional Total Marrow Irradiation Based on FLT-PET and Dual-Energy CT. [2018]

7. Germany 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. [2021]

8. United States 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. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

3'-deoxy-3'-[¹⁸F]fluorothymidine PET quantification of bone marrow response to radiation dose. [2021]

10. United States 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. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Early assessment of response to induction therapy in acute myeloid leukemia using 18F-FLT PET/CT. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

First demonstration of leukemia imaging with the proliferation marker 18F-fluorodeoxythymidine. [2016]

13. United States 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. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging for monitoring relapse of acute myeloid leukemia. [2019]