Pilot Imaging Study of Leukemia (REALIZE)

Multi-institutional Prospective Pilot Study of Radiology Evaluation of Acute Leukemia Infiltration analyZed by Experimental Imaging

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Myeloma; Ambiguous Lineage Leukemia or Lymphoma
• Intervention / Treatment: Drug: FLT

Detailed Description

This prospective trial is designed to evaluate whether investigational 18F FLT imaging can identify the burden of hematopoietic disease both subjectively (by pattern of hematopoiesis in medullary spaces) and objectively (by SUV determination).

Patients undergoing therapy for treatment of high-risk acute leukemia or myeloma will be eligible for this study. Patients may or may not have undergone myeloablative hematopoietic stem cell transplantation. Two cohorts will be accrued: patients with high risk acute leukemia and patients with myeloma. In each cohort, patients will be accrued under two arms: Arm A - patients receiving immunotherapy and Arm B - patients who are receiving standard therapy (not immunotherapy or bone marrow transplant). Therefore, the leukemia cohort will consist of patients accrued in Arm A-L (immunotherapy) or in Arm B-L (standard therapy), and the myeloma cohort will consist of patients accrued in Arm A-M (immunotherapy) or in Arm B-M (standard therapy). Because patients with high risk acute leukemia or myeloma have poor prognosis with high risk for relapse, novel ways to evaluate the success of therapies would be valuable. 18F FLT reveals hematopoietic cell proliferation and can identify residual leukemia disease. On this trial, patients will undergo 18F FLT imaging pre-therapy and during a follow-up visit post-therapy. Patients in both cohorts will be imaged (Termed baseline scan) within one week prior to receiving respective therapies (e.g. immunotherapy or standard therapy) and then imaged approximately 28 days (+/-3 days) after the therapy termed Follow-up scan. After treatment, weekly follow-ups will be conducted for these patients till the follow-up scan (28 days +/-3 days) and then the final follow-up will be conducted post-1-year (after the start of immunotherapy or standard therapy).

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Heme Onc Lead Nurse; Phone Number: 1-405-271-8777; Email: SCC-IIT-Office@ouhsc.edu

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Withdrawn
      • Children's National Health System
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Emory University
      • Contact: Kirsten M Williams, MD
      • Principal Investigator: Kirsten M Williams, MD
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73117
      • Recruiting
      • University of Oklahoma Health Sciences Center
      • Contact: Jennifer Holter Chakrabarty, MD; Phone Number: 405-271-4022; Email: jholter2@ouhsc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 4 to 80 years
2. Evidence of high-risk hematopoietic malignancy with relapsed/refractory disease: acute lymphocytic leukemia, Acute myeloid leukemia, Ambiguous lineage leukemia, myeloma
3. Karnofsky/Lansky score of ≥ 50
4. Agree to use contraceptive measures during study protocol participation (when age appropriate)
5. Patient or parent/guardian capable of providing informed consent.
6. Ability to undergo 18F FLT imaging without sedation
7. Bilirubin < 2.5 mg/dL, AST/ALT <5x upper limit of normal, Serum creatinine < 1.0 or 2x the upper limit of normal (whichever is higher)
8. Pulse oximetry of > 90% on room air
9. Ability to undergo 18F FLT imaging without sedation
10. Anticipated immunotherapy (Arm A to include patients who received immune therapy with co-enrollment on a separate protocol or other immunotherapy) and Arm B, those who received other non-immune therapies to treat their cancers (excludes HSCT but includes chemotherapy or non-HSCT radiotherapy).

Exclusion Criteria:

1. Patients with uncontrolled infections
2. Pregnancy or lactating
3. History of prior fluorothymidine allergy or intolerance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard therapy - Acute leukemia cohort; The Arm will accrue patients receiving standard therapy from the high-risk acute leukemia cohort (18 patients).	Drug: FLT; F18 labeled thymidine PET/CT scans will be performed before and after patient receives therapies.
Experimental: Immunotherapy - Acute leukemia cohort; The Arm will accrue patients receiving immunotherapy from the high-risk acute leukemia cohort (18 patients).	Drug: FLT; F18 labeled thymidine PET/CT scans will be performed before and after patient receives therapies.
Active Comparator: Standard therapy - Myeloma cohort; The Arm will accrue patients receiving standard therapy from the myeloma cohort (9 patients).	Drug: FLT; F18 labeled thymidine PET/CT scans will be performed before and after patient receives therapies.
Experimental: Immunotherapy - Myeloma cohort; The Arm will accrue patients receiving immunotherapy from the myeloma cohort (9 patients).	Drug: FLT; F18 labeled thymidine PET/CT scans will be performed before and after patient receives therapies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of 18F FLT signal uptake abnormalities with clinical pathology reports for determining the evidence of hematopoietic disease.	A proportion of patients will undergo 18F FLT imaging before and after immunotherapy or standard therapy for hematopoietic malignant disease. To detect changes in the progression of hematopoietic disease 18F FLT image scans collected pre-treatment (baseline) and post-treatment (follow-up) of patient visit at OUHSC will be compared with clinically validated evidence of hematopoietic malignant disease collected using MRD, molecular, flow and histology techniques.	day -7 to 10 days pre-treatment and +28 (+/- 3 days) post-treatment
A proportion of 18F FLT uptake in a standard region of interest in marrow to objectively identify disease status in patient with hematopoietic cancers.	For proportion of patient the analyses will be compared between two Arms of disease cohort. Arm A to include patients who received immunotherapy (immunotherapy protocol co-enrollment or other immunotherapy), and Arm B: those who received other non-immune therapies to treat their cancers (excludes HSCT). For marrow disease, the intra-medullary pattern and standard unit of uptake (SUV) will be compared pre- and post-treatment between patients in remission clinically versus those with greater disease burden, to determine if 18F FLT uptake correlates with identified clinical relapse.	day -7 to 10 days pre-treatment and +28 (+/- 3 days) post-treatment
Mean differences of 18F FLT uptake to determine extramedullary disease.	For proportion of patient undergoing 18F FLT scan, the extramedullary disease will be identified by comparing the SUV and size of lesions pre- and post-treatment. The comparisons will be done in two arms of disease cohort Arm A, i.e., to include patients who received immunotherapy (immunotherapy protocol co-enrollment or other immunotherapy), and Arm B: those who received other non-immune therapies to treat their cancers (excludes HSCT).	day -7 to 10 days pre-treatment and +28 (+/- 3 days) post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Computer assisted evaluation of leukemia and myeloma disease	To use computer algorithm to calculate if SUV changes from baseline in marrow spaces and correlates with clinical disease burden of leukemia and myeloma	day -7, and +28
Patient reported outcomes	To calculate if the scores on patient reported outcome measures are lower re: pain and anxiety with imaging than marrow tests	Day -7, and +28
Blood biomarkers	Calculate if WT1 and other biomarker values changes from baseline correlate with leukemia or myeloma disease burden by clinical assessments	Day -7, and +28

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: Emory University
• Investigators: Principal Investigator: Jennifer Holter, MD, Stephenson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: August 9, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 16, 2018

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: FLT
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: OU-SCC-REALIZE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No