FLT Imaging for Leukemia

(REALIZE Trial)

Recruiting at 1 trial location

Overseen By Heme Onc Lead Nurse

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Oklahoma

Disqualifiers: Uncontrolled infections, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging technique called 18F FLT (Fluorothymidine) to determine its effectiveness in detecting signs of blood cancers like leukemia and myeloma after treatments such as immunotherapy. Researchers aim to discover if this imaging method can identify cancer cells that remain undetected. Participants include individuals with high-risk blood cancers who have relapsed or whose disease has not responded to standard treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to benefit from this innovative approach.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that FLT imaging is generally safe for people. Previous studies have examined its effectiveness and provided safety information. These studies suggest that participants handle FLT imaging easily, with no major side effects reported. Participants did not experience significant issues, indicating that the imaging process is manageable. Overall, the evidence suggests that FLT imaging is a safe choice for clinical trial participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about FLT imaging for leukemia because it offers a new way to monitor and evaluate treatment responses in real-time. Unlike traditional methods that often rely on invasive biopsies and slower diagnostic tests, FLT imaging uses a radiolabeled tracer that can highlight active cancer cells in the body through PET scans, providing quicker and more precise insights. This technique could allow doctors to adjust treatments more rapidly and effectively, potentially improving outcomes for patients with high-risk acute leukemia and myeloma.

What evidence suggests that FLT imaging is effective for detecting leukemia?

Research has shown that FLT imaging can help detect leukemia and myeloma. In studies with patients who have acute leukemia, FLT PET imaging revealed changes that helped doctors assess how the disease responded to treatment. This trial includes an arm where participants with high-risk acute leukemia will receive immunotherapy, and FLT imaging will monitor treatment response. For myeloma, FLT imaging appears promising for identifying patients at higher risk. Although less data exists on myeloma, it remains a valuable method for diagnosing and assessing cancer activity. Participants in this trial's myeloma cohort will also be monitored using FLT imaging, whether they receive standard therapy or immunotherapy. Overall, FLT imaging is becoming a useful tool for monitoring and predicting outcomes for these conditions. ^{1 6 7 8 9}

Who Is on the Research Team?

Jennifer Holter, MD

Principal Investigator

Stephenson Cancer Center

Are You a Good Fit for This Trial?

This trial is for people aged 4-80 with high-risk blood cancers like acute lymphocytic leukemia, who have relapsed or are not responding to treatment. They must be able to undergo FLT imaging without sedation, have certain levels of liver and kidney function, a decent quality of life score (Karnofsky/Lansky ≥ 50), and agree to use contraception if applicable.

Inclusion Criteria

My blood cancer has returned or is not responding to treatment.

I am able to live with some level of independence.

I (or my guardian) can understand and agree to the study's terms.

Exclusion Criteria

I do not have any infections that are currently uncontrolled.

History of prior fluorothymidine allergy or intolerance

Pregnancy or lactating

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Imaging

Participants undergo 18F FLT imaging to establish baseline before therapy

1 week

1 visit (in-person)

Treatment

Participants receive either immunotherapy or standard therapy

4 weeks

Weekly follow-ups (in-person)

Follow-up Imaging

Participants undergo 18F FLT imaging to assess treatment response

1 week

1 visit (in-person)

Long-term Follow-up

Participants are monitored for safety and effectiveness post-treatment

1 year

Final follow-up visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• FLT

Trial Overview The study tests whether abnormalities in FLT imaging signal uptake match up with other clinical evidence of blood cancer after treatments such as immunotherapy. Participants will either receive immunotherapy (Arm A) or non-immune therapies like chemotherapy (Arm B).

How Is the Trial Designed?

Group I: Immunotherapy - Myeloma cohort Experimental Treatment 1 Intervention

The Arm will accrue patients receiving immunotherapy from the myeloma cohort (9 patients).

Group II: Immunotherapy - Acute leukemia cohort Experimental Treatment 1 Intervention

The Arm will accrue patients receiving immunotherapy from the high-risk acute leukemia cohort (18 patients).

Group III: Standard therapy - Myeloma cohort Active Control 1 Intervention

The Arm will accrue patients receiving standard therapy from the myeloma cohort (9 patients).

Group IV: Standard therapy - Acute leukemia cohort Active Control 1 Intervention

The Arm will accrue patients receiving standard therapy from the high-risk acute leukemia cohort (18 patients).

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Published Research Related to This Trial

The study developed a monoclonal antibody (MAb 10G6) that specifically targets the FLT3 molecule found on leukemia cells, showing potential for use in leukemia diagnosis and therapy.

MAb 10G6 was effective in inhibiting the growth and movement of leukemia cells and inducing their death, suggesting it could be a valuable therapeutic tool for treating FLT3-positive leukemias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-human FLT3 monoclonal antibody that inhibits proliferation of monocytic leukemia cell line SHI-1. Ju, S., Xue, Z., Ju, S., et al.[2011]

In a study involving 19 patients (15 with tumor recurrence and 4 with radionecrosis), the metabolic flux (K (FLT)) from 3'-Deoxy-3'-[18F]fluorothymidine ([18F]FLT) PET scans was effective in distinguishing between glioma recurrence and radionecrosis, outperforming traditional imaging methods.

The study found that K (FLT) and the phosphorylation rate (k (3)) were significant indicators for differentiating the two conditions, while standard uptake values and visual analyses of both [18F]FLT and FDG PET scans did not show significant differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NCI-sponsored trial for the evaluation of safety and preliminary efficacy of 3'-deoxy-3'-[18F]fluorothymidine (FLT) as a marker of proliferation in patients with recurrent gliomas: preliminary efficacy studies. Spence, AM., Muzi, M., Link, JM., et al.[2022]

In a study using C3H/HeN mice with squamous cell carcinomas, FLT PET imaging showed a significant reduction in tumor uptake 24 hours after radiation treatment, indicating its potential as an effective tool for monitoring early responses to radiation therapy.

Unlike FLT, FDG PET imaging did not show significant changes in tumor uptake after radiation, suggesting that FLT may provide more sensitive insights into the effects of radiation on tumor proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of 3'-deoxy-3'-[18F]fluorothymidine PET to monitor early responses to radiation therapy in murine SCCVII tumors. Yang, YJ., Ryu, JS., Kim, SY., et al.[2018]

FLT3, a novel cytokine receptor, is predominantly expressed in pre-B cell and myeloid leukemia cell lines, and its ligand (FLT3 ligand) can stimulate cell proliferation in certain myeloid leukemia cases, particularly in the MUTZ-2 and OCI-AML-5 cell lines.

Despite high FLT3 receptor expression in pre-B-ALL cells, these cells did not proliferate in response to FLT3 ligand, indicating that receptor expression alone does not guarantee responsiveness, and further research is needed to explore the full role of FLT3 signaling in leukemogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of FLT3 ligand on human leukemia cells. I. Proliferative response of myeloid leukemia cells. Dehmel, U., Zaborski, M., Meierhoff, G., et al.[2013]

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 20 adult AML patients, FLT3-ITD was found to be a suitable target for monitoring minimal residual disease (MRD) using real-time quantitative PCR, showing comparable effectiveness to other markers like NPM1 mutation and WT1 overexpression in 85% of cases.

FLT3-ITD levels measured after induction chemotherapy were predictive of the duration of complete remission, suggesting its potential utility in guiding treatment decisions for AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal residual disease monitoring based on FLT3 internal tandem duplication in adult acute myeloid leukemia. Abdelhamid, E., Preudhomme, C., Helevaut, N., et al.[2021]

Flt3L levels are significantly associated with treatment outcomes in acute myeloid leukemia (AML), where higher levels at day 26 post-chemotherapy correlate with better overall survival and event-free survival in patients with Flt3 mutations.

Monitoring Flt3L is a promising noninvasive method to assess disease status and potential relapse in AML patients, as it reflects the response to treatment and can guide clinical decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum Flt3 ligand is a biomarker of progenitor cell mass and prognosis in acute myeloid leukemia. Milne, P., Wilhelm-Benartzi, C., Grunwald, MR., et al.[2020]

The study demonstrated that 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) microPET scans are reproducible in monitoring tumor proliferation, with a coefficient of variation of 14% for %ID/g values between scans performed 6 hours apart.

This reproducibility allows for reliable serial studies to assess therapy response or for drug screening in preclinical settings, indicating that (18)F-FLT can be a valuable tool in cancer research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility of 3'-deoxy-3'-(18)F-fluorothymidine microPET studies in tumor xenografts in mice. Tseng, JR., Dandekar, M., Subbarayan, M., et al.[2019]

In a study of 85 patients with acute myeloid leukemia (AML), including 23 in complete remission, FLT3 mRNA expression was evaluated to assess its role in monitoring minimal residual disease (MRD).

The results indicated that FLT3 expression has limited utility as a prognostic marker and for tracking MRD in AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited value of FLT3 mRNA expression in the bone marrow for prognosis and monitoring of patients with acute myeloid leukemia. Kainz, B., Fonatsch, C., Schwarzinger, I., et al.[2019]

The experimental chemotherapeutic agent TP202377 significantly inhibited cell proliferation in sensitive A2780 ovarian cancer tumors, as shown by a 46% decrease in [18F]FLT uptake at 6 hours post-treatment, indicating its efficacy in this model.

In contrast, TP202377 did not affect tumor growth or [18F]FLT uptake in resistant A2780/Top216 and SW620 colon cancer models, demonstrating the potential for [18F]FLT PET to non-invasively differentiate between sensitive and resistant tumors shortly after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]FLT PET for non-invasive assessment of tumor sensitivity to chemotherapy: studies with experimental chemotherapy TP202377 in human cancer xenografts in mice. Munk Jensen, M., Erichsen, KD., Björkling, F., et al.[2021]

Quantitative measurements using [(18)F]FLT PET for monitoring tumor proliferation in patients with non-small-cell lung cancer and head-and-neck cancer showed excellent reproducibility, with intraclass correlation coefficients (ICCs) ranging from 0.92 to 0.98 for various metrics.

Changes greater than 15% in SUV(41%), 20-25% in SUV(max), and 20-25% in Patlak-derived K(i) are significant indicators of treatment effects, making [(18)F]FLT PET a reliable tool for assessing tumor response in individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility of quantitative 18F-3'-deoxy-3'-fluorothymidine measurements using positron emission tomography. de Langen, AJ., Klabbers, B., Lubberink, M., et al.[2019]

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 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is effective for detecting prostate cancer in a mouse model, showing the highest uptake in tumors at 2 hours post-injection, which indicates its potential as a reliable imaging agent.

(18)F-FLT can also monitor the therapeutic effects of androgen ablation therapy, as evidenced by a significant reduction in tracer uptake in tumors following treatment, correlating with actual tumor size changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring of therapy in androgen-dependent prostate tumor model by measuring tumor proliferation. Oyama, N., Ponde, DE., Dence, C., et al.[2019]

In a study of 61 patients with untreated high-grade non-Hodgkin lymphoma, early interim PET scans using the tracer (18)F-FLT were found to be strong predictors of progression-free survival (PFS) and overall survival (OS), with significant cutoff values indicating worse outcomes for patients with high uptake levels.

The interim (18)F-FLT PET scans showed better prognostic value compared to baseline and final scans, suggesting that this imaging technique can effectively identify patients who may not respond well to treatment, even if they appear to have a clinical complete response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early determination of prognosis by interim 3'-deoxy-3'-18F-fluorothymidine PET in patients with non-Hodgkin lymphoma. Lee, H., Kim, SK., Kim, YI., et al.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02392429

Study Details | NCT02392429 | FLT PET/CT in Measuring ... This phase II trial studies fluorothymidine F 18 (FLT) positron emission tomography (PET)/computed tomography (CT) in measuring response in patients with ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/54/supplement_2/1561

Imaging acute myeloid leukemia with [F-18] fluorothymidine PET Conclusions FLT PET imaging in AML shows increased marrow uptake without significant heterogeneity. At mid-therapy the FLT uptake levels changed throughout the ...

3. withpower.com withpower.com/trial/phase-3-leukemia-11-2015-d24dc

FLT PET/CT Imaging for Acute Myeloid Leukemia In a pilot study involving 10 patients with acute myeloid leukemia (AML), the imaging technique using 18F-fluorothymidine (FLT) PET was effective in visualizing ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10801569/

Emerging Role of [18F]FLT PET/CT in Lymphoid Malignancies [18F]FLT PET/CT has the potential for predicting patient outcomes and guiding treatment strategies. Its use in early response assessment after ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212610003024

Early assessment of treatment response in patients with ... This pilot study suggests that FLT PET imaging during induction chemotherapy may serve as an early biomarker of treatment response in AML. Introduction.

6. withpower.com withpower.com/trial/phase-1-leukemia-9-2021-a3e08

FLT Imaging for Leukemia (REALIZE Trial) While these studies primarily focus on its effectiveness, they also provide some safety data, suggesting it is generally safe for use in humans. ... Group II: ...

7. mayo.edu mayo.edu/research/clinical-trials/cls-20260181

FLT PET/CT in Measuring Response in Patients With ... FLT PET/CT in Measuring Response in Patients With Previously Untreated Acute Myeloid Leukemia ... safety, side effects, optimal dosages and risks/benefits.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11791676/

18F-FLT PET and Blood-based Biomarkers for Identifying ... Flourine 18 fluorothymidine PET has the potential to help identify the specific area of graft versus host disease (GVHD), which has utility in ...

9. aacrjournals.org aacrjournals.org/clincancerres/article/17/5/1099/76710/Imaging-Colon-Cancer-Response-Following-Treatment

Imaging Colon Cancer Response Following Treatment with ... NCI-sponsored trial for the evaluation of safety and preliminary efficacy of FLT as a marker of proliferation in patients with recurrent gliomas: safety studies.