FLT PET/CT Imaging for Acute Myeloid Leukemia

Recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Disqualifiers: APL, Pregnancy, Allergic reaction, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 29

Duration: 2-4 weeks

87 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies fluorothymidine F 18 (FLT) positron emission tomography (PET)/computed tomography (CT) in measuring response in patients with previously untreated acute myeloid leukemia. FLT is a radioactive substance that may "light up" where cancer is in the body. FLT is injected into the blood and builds up in cells that are dividing, including cancer cells. Diagnostic procedures, such as PET/CT, may help measure a patient's response to earlier treatment.

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 is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Cytarabine, Cytosar-U, Depocyt, Tarabine PFS, Fluorothymidine F-18, FLT, Fluorothymidine F-18, 18F-FLT for treating acute myeloid leukemia?

Research shows that 18F-FLT PET/CT imaging can help assess how well patients with acute myeloid leukemia respond to treatment early on, which can predict their clinical outcomes. Additionally, 18F-FLT has been effective in imaging leukemia in mice, suggesting its potential usefulness in monitoring disease activity in humans. ^{1 2 3 4 5}

Is FLT PET/CT Imaging for Acute Myeloid Leukemia safe for humans?

Cytarabine, a key drug used in treating acute myeloid leukemia, has been studied for its safety and effectiveness. Genetic factors can influence how patients respond to cytarabine, affecting both its effectiveness and the risk of side effects. Understanding these genetic differences can help in adjusting doses to minimize side effects while maintaining treatment effectiveness. ^{6 7 8 9 10}

How is Cytarabine treatment for acute myeloid leukemia unique?

Cytarabine is unique because it is often used in combination with advanced imaging techniques like FLT PET/CT to assess early response to treatment in acute myeloid leukemia, helping to predict clinical outcomes more effectively. ^{1 2 3 4 11}

Research Team

Robert Jeraj

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults with newly diagnosed acute myeloid leukemia who haven't been treated yet. They must be able to lie still for a PET scan, not be pregnant or breastfeeding, and have no history of allergic reactions to similar compounds as the study drug. Participants need a good performance status and heart function, can't weigh more than the scanner limit, and shouldn't have certain types of leukemia.

Inclusion Criteria

Patients must have left ventricular ejection fraction (LVEF) > 45% or within institutional normal limits

Patient must NOT have a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-fluorothymidine

Patient must NOT weigh more than the maximum weight limit for the PET/CT table for the scanner(s) to be used at each center

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive anthracycline IV on days 1-3 and cytarabine IV on days 1-7 for up to 2 courses, followed by FLT PET/CT imaging

2-4 weeks

Multiple visits for chemotherapy and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment, including survival outcomes

Up to 1 year

Follow-up visits at day 28-35 and up to 1 year

Long-term Follow-up

Participants are monitored for relapse-free survival and overall survival

Up to 4 years

Treatment Details

Interventions

• Cytarabine
• Fluorothymidine F-18

Trial Overview The trial tests how well FLT PET/CT scans measure treatment response in patients receiving their first round of chemotherapy for acute myeloid leukemia. FLT is a radioactive tracer that highlights dividing cells like cancer on scans.

Participant Groups

Group I: Diagnostic (anthracycline, cytarabine, FLT PET/CT) Experimental Treatment 9 Interventions

Patients receive anthracycline IV on days 1-3 and cytarabine IV on days 1-7 for up to 2 courses. Patients then undergo FLT PET/CT within 3 days before or after the nadir bone marrow biopsy (between days 10-17 after initiation of first induction cycle and prior to reinduction). Patients may undergo an optional FLT PET/CT prior to induction chemotherapy if it does not interfere with commencement of treatment. Patients also undergo bone marrow biopsy and aspiration and blood sample collection during screening and on the trial.

Cytarabine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Meningeal leukemia

Approved in European Union as Depocyt for:

• Lymphomatous meningitis

Approved in Canada as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

In a study of 52 lymphoma patients, F-18-Fluorothymidine (FLT) PET/CT showed similar efficacy to F-18-FDG PET/CT in detecting recurrent or residual disease, with both imaging methods demonstrating significant differences in uptake between malignant and benign lesions.

While FLT had slightly better performance in distinguishing between benign and malignant lesions, it is not recommended as a standalone diagnostic tool and may only be useful in specific cases as a complement to FDG imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of 18F-FLT PET/CT in suspected recurrent or residual lymphoma: final results of a pilot prospective trial. Zanoni, L., Broccoli, A., Lambertini, A., et al.[2020]

The study demonstrated that the PET tracer 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) shows significantly higher uptake in human leukemia cells compared to fluorine-18-fluorodeoxyglucose ((18)F-FDG), indicating its potential for better imaging of tumor proliferation.

In mouse models of chronic myeloid leukemia, (18)F-FLT PET imaging provided a higher tumor-to-non-tumor count ratio than (18)F-FDG PET, suggesting that (18)F-FLT may be more effective for metabolic imaging of this type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging proliferation in human leukemia-tumor bearing mice with (18)F-FLT: Comparison with (18)F-FDG PET. Lu, L., Jiang, L., Guan, H., et al.[2016]

Clofarabine combined with cytarabine (Ara-C) showed a 53% overall response rate in 30 adult patients with relapsed or refractory acute myeloid leukemia (AML), including a 47% complete remission rate, demonstrating its efficacy in both untreated and previously treated patients.

The treatment was particularly beneficial for older patients with a history of cardiovascular disease, providing a viable option for remission induction that could lead to curative hematopoietic stem cell transplantation, despite a 30-day mortality rate of 20%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Agura, E., Cooper, B., Holmes, H., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

3. Germany pubmed.ncbi.nlm.nih.gov

Role of 18F-FLT PET/CT in suspected recurrent or residual lymphoma: final results of a pilot prospective trial. [2020]

4. Greece pubmed.ncbi.nlm.nih.gov

Imaging proliferation in human leukemia-tumor bearing mice with (18)F-FLT: Comparison with (18)F-FDG PET. [2016]

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

The importance of FLT3 mutational analysis in acute myeloid leukemia. [2021]

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

Combined interaction of multi-locus genetic polymorphisms in cytarabine arabinoside metabolic pathway on clinical outcomes in adult acute myeloid leukaemia (AML) patients. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Genetic factors influencing cytarabine therapy. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Intracellular cytarabine triphosphate in circulating blasts post-treatment predicts remission status in patients with acute myeloid leukemia. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Expression Levels of Human Equilibrative Nucleoside Transporter 1 and Deoxycytidine Kinase Enzyme as Prognostic Factors in Patients with Acute Myeloid Leukemia Treated with Cytarabine. [2017]

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

Imaging proliferation to monitor early response of lymphoma to cytotoxic treatment. [2021]