18-FLT PET/MR Imaging to Predict Graft Failure and GVHD in Bone Marrow Transplant Patients

NCT03546556 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: LCCC 1714
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic HSCT is potentially curative for numerous high risk hematologic malignancies and offers several advantages over traditional chemotherapy. First, higher doses of cytotoxic chemotherapy and/or irradiation can be given since patients are subsequently rescued from the severe myelosuppression induced by the pre-transplant conditioning regimen by the infusion of healthy hematopoietic stem cells. Second and perhaps more importantly, mature T cells contained in the graft are able to mount immune responses against residual cancer cells surviving the conditioning regimen due to major and/or minor MHC disparities between the donor and recipient. Unfortunately, the allo-immune responses driving the GVL effect are typically not specific for malignant cells. As a consequence, donor immune cells attack normal host tissues resulting in a process known as acute graft-versus-host disease (GVHD). Acute GVHD is primarily T cell driven, usually occurs within the first few months after transplant, and results in skin rash, diarrhea, cholestatic liver damage, and, on occasion, acute lung injury.

Conditions

Graft Vs Host Disease

Outcome Measures

Primary Outcomes (2)

• Overall FLT-PET Bone Marrow Signal

  Compare the overall FLT-PET bone marrow signal on transplant day +25 between allogeneic stem cell transplant recipients who do and do not go on to achieve complete donor bone marrow reconstitution by transplant day +35.

  35 Days (Approximate)

• Overall FLT-PET Signal Intensity within Host Secondary Lymphoid Sites

  Compare the overall FLT-PET signal intensity within host secondary lymphoid sites on transplant day +60 between allogeneic stem cell transplant recipients who do and do not develop acute GVHD by transplant day +100.

  100 Days (Approximate)

Secondary Outcomes (10)

• Overall Long-Term FLT-PET Bone Marrow Signal

  100 Days (Approximate)

• Overall Long-Term FLT-PET Signal Intensity within Host Secondary Lymphoid Sites

  100 Days (Approximate)

• Differences in FLT Uptake in Autologous HSCT and Allogeneic HSCT Patients

  100 Days (Approximate)

• Strength of FLT-PET Signal and Transfusion Independence

  35 Days (Approximate)

• Strength of the FLT-PET Signal and Bone Marrow Cellularity

  35 Days (Approximate)

Study Arms (2)

Allogeneic

EXPERIMENTAL

A total of 12 patients who have undergone allogenic bone marrow transplantation will undergo Fluorothymidine FLT-PET-MRI imaging on two separate occasions.

Drug: Fluorothymidine (FLT)

Autologous

EXPERIMENTAL

3 patients undergoing autologous stem cell transplant will also undergo Fluorothymidine FLT-PET-MRI imaging the same two time points in order to determine how much of the FLT signal observed after allogeneic transplant is unique to that population and the result of allo-antigen driven T cell expansion.

Drug: Fluorothymidine (FLT)

Interventions

Fluorothymidine (FLT) DRUG

A total of 12 patients who have undergone allogenic bone marrow transplantation will undergo FLT-PET-MRI imaging on two separate occasions. In addition to the 12 allogenic transplant patients, 3 patients undergoing autologous stem cell transplant will also be imaged the same two time points in order to determine how much of the FLT signal observed after allogeneic transplant is unique to that population and the result of allo-antigen driven T cell expansion.

Also known as: 18F-FLT, 3'-deoxy-3'-(18F) fluorothymidine, 3'-deoxy-3'-[18F]fluorothymidine, fluorothymidine F 18, fluorothymidine F-18, Thymidine, 3'-deoxy-3'-(18F)fluoro-

Allogeneic; Autologous

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing allogeneic bone marrow transplant for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome
• Allogeneic transplant patients receiving either a fully myeloablative or reduced intensity chemotherapy +/- total body irradiation (TBI) conditioning regimen are eligible.
• Allogeneic transplant patients receiving stem cells from a matched related, matched unrelated, mismatched unrelated, mismatched related (including haplotype matched) donors are eligible
• Allogeneic transplant patients must be in a complete morphologic remission prior to transplant
• Patients undergoing autologous bone marrow transplant for multiple myeloma
• Myeloma patients must have achieved at least a very good partial remission prior to transplant and exhibit fewer than 10% plasma cells in their pre-transplant marrow biopsy
• At least 18 years of age
• Negative urine pregnancy test in women of child-bearing potential

You may not qualify if:

• Any woman who is pregnant or has reason to believe she is pregnant or any woman who is lactating.
• Condition that makes MRI unsafe (e.g., cardiac pacemaker, epicardial pacemaker leads, cochlear implants, metal aneurysm clip, metal halo devices)
• Inability to tolerate MRI (e.g., unable to lie flat for \> 1 hour, severe claustrophobia)
• Known allergy to fluorothymidine
• Creatinine clearance \< 40 ml/min, as estimated by the Cockcroft-Gault formula
• Body Mass Index (BMI) \> 35
• Poorly controlled diabetes mellitus (fasting blood glucose \> 500 mg/dl)
• Institutionalized subject (prisoner or nursing home patient)
• Critically ill or medically unstable
• Currently hospitalized (All FLT PET/MR scans will be obtained in the outpatient setting)

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (1)

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Related Links

• UNC Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

alovudine

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Z Lee, MD/PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2018
• First Posted: June 6, 2018
• Study Start: January 1, 2017
• Primary Completion: March 12, 2020
• Study Completion: March 12, 2020
• Last Updated: December 10, 2024

Record last verified: 2024-12

Locations

US (1)