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

Trial Summary

What is the purpose of this trial?

This is a prospective pilot study, the primary aim of which is to determine whether the presence of 18F FLT imaging signal uptake abnormalities correlate with clinically validated evidence of hematopoietic malignant disease (e.g. MRD, molecular, flow or histology) after immunotherapy and other treatments.

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 FLT, 18F-FLT, Fluorothymidine, [F-18] Fluorothymidine for leukemia?

Research shows that 18F-FLT is effective in imaging tumor growth in leukemia, as it has a higher uptake in leukemia cells compared to another imaging agent, 18F-FDG. This suggests that 18F-FLT could be useful for monitoring leukemia progression and response to treatment. ^{1 2 3 4 5}

Is FLT imaging safe for humans?

The safety of FLT imaging in humans has been evaluated in clinical studies, such as those sponsored by the National Cancer Institute, which looked at its use in patients with recurrent gliomas. While these studies primarily focus on its effectiveness, they also provide some safety data, suggesting it is generally safe for use in humans. ^{5 6 7 8 9}

How does the FLT Imaging treatment for leukemia differ from other treatments?

FLT Imaging for leukemia is unique because it focuses on the FLT3 molecule, which is a target for monitoring minimal residual disease (MRD) and assessing treatment response in acute myeloid leukemia (AML). This approach uses specific markers like FLT3-ITD to predict remission duration and can provide valuable insights into the effectiveness of chemotherapy, making it different from standard treatments that may not use such targeted molecular markers. ^{10 11 12 13 14}

Research Team

Jennifer Holter, MD

Principal Investigator

Stephenson Cancer Center

Eligibility Criteria

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

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)

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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 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]

References

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

Reproducibility of quantitative 18F-3'-deoxy-3'-fluorothymidine measurements using positron emission tomography. [2019]

2. 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]

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

Monitoring of therapy in androgen-dependent prostate tumor model by measuring tumor proliferation. [2019]

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

Early determination of prognosis by interim 3'-deoxy-3'-18F-fluorothymidine PET in patients with non-Hodgkin lymphoma. [2016]

5. 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]

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

Reproducibility of 3'-deoxy-3'-(18)F-fluorothymidine microPET studies in tumor xenografts in mice. [2019]

7. United States 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. [2022]

8. United States 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. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Use of 3'-deoxy-3'-[18F]fluorothymidine PET to monitor early responses to radiation therapy in murine SCCVII tumors. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Minimal residual disease monitoring based on FLT3 internal tandem duplication in adult acute myeloid leukemia. [2021]

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

Serum Flt3 ligand is a biomarker of progenitor cell mass and prognosis in acute myeloid leukemia. [2020]

12. Italy 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. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Effects of FLT3 ligand on human leukemia cells. I. Proliferative response of myeloid leukemia cells. [2013]

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

Anti-human FLT3 monoclonal antibody that inhibits proliferation of monocytic leukemia cell line SHI-1. [2011]