FLT PET/CT Imaging for Acute Myeloid Leukemia

Not currently recruiting at 14 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assess how well patients with untreated acute myeloid leukemia (AML) respond to treatment. It employs a special imaging technique called FLT PET/CT, which highlights cancer cells by injecting a radioactive substance. Participants receive chemotherapy drugs like cytarabine (also known as Cytosar-U, Depocyt, or Tarabine PFS), and the imaging evaluates the effect on cancer. The trial seeks participants who have not received prior treatment for AML and are eligible for intensive chemotherapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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 prior data suggests that FLT PET/CT imaging is safe for patients with acute myeloid leukemia?

Research has shown that cytarabine is often used with other drugs to treat leukemia. Patients generally tolerate it well, but it can have side effects. Some studies reported complete remission rates between 18% and 41% with cytarabine. However, like many cancer treatments, it can cause unwanted reactions, such as low blood cell counts, nausea, and mouth sores.

Cytarabine is part of the standard treatment for certain types of leukemia, so its safety is fairly well understood. While no treatment is without risks, healthcare providers know how to manage cytarabine's side effects.

Discussing any concerns about side effects or risks with medical professionals is important when considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it combines FLT PET/CT imaging with standard chemotherapy treatments to potentially improve the management of acute myeloid leukemia (AML). Unlike traditional imaging methods, FLT PET/CT offers a detailed view of cellular activity, which could help in assessing how well the treatment is working much earlier than usual. This advanced imaging technique may allow doctors to tailor treatments more precisely and make quicker decisions about adjusting therapy, potentially leading to better patient outcomes. By integrating this innovative imaging with chemotherapy, the trial hopes to provide a clearer picture of treatment effectiveness and improve patient care for those battling AML.

What evidence suggests that FLT PET/CT is effective for measuring response in acute myeloid leukemia?

Research has shown that cytarabine, which participants in this trial will receive, effectively treats acute myeloid leukemia (AML). In treatment plans, it can lead to high cure rates, with some combinations achieving success in 75-80% of certain AML cases. One study found a complete response rate of 95.5% with a standard treatment that includes cytarabine. Although results can vary, these findings highlight cytarabine’s strong role in fighting AML, making it a trusted option in leukemia treatment plans. ^{2 4 5 6 7}

Who Is on the Research Team?

Robert Jeraj

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7900255/

Acute myeloid leukemia: current progress and future ... The new regimens utilizing fludarabine, high-dose cytarabine and GO, with or without idarubicin, may be better, producing cure rates of 75–80+%. The CBF AML ...

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/5922/505830/Real-World-Outcomes-of-CPX-351-Compared-to

Real World Outcomes of CPX-351 Compared to Traditional ... Twenty-five percent of patients achieved CR/CRi in the CPX-351 arm with one induction cycle, compared to 95.5% in the 7+3 group. Median ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6839888/

A real-world study of clofarabine and cytarabine ... Progression-free survival (PFS) at 2 years was 16% (95% CI 8–27%) and overall survival (OS) at 2 years was 21% (95% CI 11–33%) for all patients. The 30-day ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123125225

Real World Outcomes of CPX-351 Compared to Traditional ... Introduction: Outcomes in patients with secondary AML (sAML) are inferior to those with de novo AML which has led investigators to seek ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT74020

Etoposide and cytarabine as an effective and safe ... A combination of mitoxantrone, etoposide and cytarabine (MEC) is commonly used as second-line therapy and confers response rates of 18-28% with a median OS of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40348597/

The Clinical Safety and Efficacy of Cytarabine ... Results: CPX-351 exhibited an adverse event profile that was comparable to that of conventional chemotherapy. It resulted in complete remission rates of 18%-41% ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01802333

Cytarabine and Daunorubicin Hydrochloride or Idarubicin ... ARM II: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may ...