18F- Fluorothymidine to Evaluate Treatment Response in Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00775268
First received: October 17, 2008
Last updated: July 2, 2014
Last verified: December 2013
  Purpose

Background:

  • Positron emission tomography (PET) uses radioactive substances called tracers to locate areas of cancer in the body. For this test, the patient is given an injection of tracer and lies in a large donut-shaped scanner that detects where in the body the radioactivity accumulates. Computed tomography (CT) scans use low dose x-rays that help to better localize where the radioactive tracer is concentrating. PET/CT scans are usually done in lymphoma patients before treatment starts and at the end of treatment to evaluate the response to therapy.
  • PET scans typically use a sugar-like radioactive tracer called fluorodeoxyglucose (FDG) and low-dose x-rays. Sometimes, however, FDG PET scans show what looks like active disease and presence of a mass after chemotherapy even when there are no live cancer cells. Doctors have particular problems in evaluating response to treatment when this happens because they can t tell if the mass is active cancer or just dead tumor cells.
  • An experimental tracer called 18F- fluorothymidine (FLT) has high uptake in active tumor cells and may be better able to evaluate treatment response.

Objectives:

- To test the use of FLT PET/CT imaging in assessing treatment response in patients with lymphoma.

Eligibility:

- Patients 18 years of age or older who are enrolled in a lymphoma therapy study at the NIH Clinical Center or in the CALGB 50330 study at another location.

Design:

- There are two arms in this study:

  • The first arm evaluates FLT as an early predictor of tumor response to therapy. Patients are imaged with FLT and FDG PET before starting treatment, following two cycles of therapy and after treatment ends.
  • The second arm evaluates the ability of FLT to distinguish if a mass that remains after treatment is active cancer or dead tissue. Patients who have completed treatment and in whom FDG PET shows a remaining tumor mass are imaged with FLT PET. Following the scan, the tumor is biopsied for verification.

Condition Intervention Phase
Lymphoma
Procedure: Biopsy
Radiation: Fluordeoxyglucose F 18
Other: [3'-deoxy-3'-[F-18] fluorothymidine
Procedure: computed tomography
Procedure: fine-needle aspiration
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: A Pilot Study of 18F Fluorothymidine (FLT) PET/CT in Lymphoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Diagnostic accuracy of 3'-deoxy-3'-[18F] fluorothymidine (FLT PET/CT scans as an early indicator of complete response to therapy. [ Designated as safety issue: No ]
  • Diagnostic accuracy of FLT PET/CT scans in the evaluation of residual masses after therapy. [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of the diagnostic accuracy of FLT and fludeoxyglucose F 18 (FDG) PET/CT scans as indicators of tumor response to therapy [ Designated as safety issue: No ]
  • Evaluation of whether FLT tumor uptake either prior to therapy and/or after completion of therapy are independent predictors of complete response to therapy [ Designated as safety issue: No ]
  • Evaluation of whether FLT tumor uptake either prior to therapy and/or after completion of therapy are independent predictors of progression-free survival [ Designated as safety issue: No ]
  • Evaluation of whether there is a significant difference in tumor, selected normal organs, and mediastinal blood pool FDG standardized uptake values (SUV) at 1- and 2-hours post-injection [ Designated as safety issue: No ]
  • Evaluation of whether there is a significant difference in tumor, selected normal organs, and mediastinal blood pool FLT dynamic influx parameter (Ki) SUV at 1- and 2-hours post-injection [ Designated as safety issue: No ]
  • Diagnostic accuracy of percent change in SUV between pre-treatment and mid-treatment FLT PET/CT as an indicator of complete response to therapy [ Designated as safety issue: No ]
  • Diagnostic accuracy of percent change in SUV between pre-treatment and mid-treatment FLT PET/CT as an indicator of progression-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: September 2008
Estimated Study Completion Date: June 2016
Arms Assigned Interventions
Experimental: Group A
Patients undergo 3'-deoxy-3'-[18F] fluorothymidine (FLT) and fludeoxyglucose F 18 (FDG) PET/CT scans at baseline, after 2 courses of chemotherapy, and after completion of chemotherapy. Patients with residual FDG-positive mass after completion of therapy may be enrolled in group B.
Radiation: Fluordeoxyglucose F 18
Undergo scans
Other: [3'-deoxy-3'-[F-18] fluorothymidine
Undergo scans
Procedure: computed tomography
Undergo scans
Experimental: Group B
Patients undergo an FLT PET/CT scan within 2 weeks after completion of chemotherapy. Patients also undergo a biopsy or fine-needle aspiration, if clinically indicated.
Procedure: Biopsy
Biopsy taken
Other: [3'-deoxy-3'-[F-18] fluorothymidine
Undergo scans
Procedure: computed tomography
Undergo scans
Procedure: fine-needle aspiration
sample collected

Detailed Description:

Background:

  • FLT PET/CT has been shown to correlate with the rate of cellular/tumor proliferation.
  • The Imaging Subcommittee of the International Harmonization Project in Lymphoma recommends performing FDG PET at least 3 weeks, and preferably 6-8 weeks after chemotherapy or chemoimmunotherapy therapy and 8- 12 weeks after radiation or chemoradiation therapy due to high FDG accumulation in inflammatory tissues.
  • FLT uptake in inflammatory lesions is less prominent than FDG and it is likely that FLT PET/CT can better differentiate inflammation from tumor.
  • FLT PET/CT imaging is expected to better differentiate between treatment induced inflammation and malignancy and should enable early prediction of therapeutic response.
  • FLT PET/CT imaging is expected to differentiate between residual inflammatory residual masses from residual malignancy and therefore guide appropriate treatment.

Primary Objectives:

  • To estimate the diagnostic accuracy of FLT PET/CT as an early indicator of complete response to therapy in B and T cell lymphoma.
  • To estimate the diagnostic accuracy of FLT PET/CT in the evaluation of residual masses after therapy.

Eligibility:

  • Participant must be enrolled in a lymphoma therapy study at the NIH Clinical Center OR be enrolled in the CALGB 50303 study at another site OR undergoing a new course of treatment of lymphoma at another facility. The NCI Laboratory of Pathology will confirm diagnosis for subjects enrolled at all CALGB study sites.
  • Participants must have a clinical course consistent with lymphoma and have available documentation of lymphoma from either the NCI or from an outside pathology laboratory.
  • Subjects enrolling in the early response arm must undergo baseline FLT PET prior to receiving a new course of lymphoma therapy.
  • Subjects enrolling in the residual mass evaluation arm can be enrolled at the time the FDG avid residual mass is discovered (i.e. no pre-therapy FLT image is required).
  • Subjects can enroll in both arms of the study.
  • Participant must be 18 years or older.
  • ECOG Performance score of 0 or 1.
  • SGOT, SGPT less than 5 times ULN.
  • bilirubin less than or equal to 2 times ULN.

Design:

  • There are 2 arms in this study

    • The first arm will assess of FLT as an early predictor of tumor response to therapy (treatment naive or recurrent disease). Subjects are imaged with FLT and FDG PET pre-therapy, following 2 cycles of therapy and post therapy.
    • The second arm will assess lymphoma patients with FDG PET positive residual mass. Subjects are imaged with FLT PET prior to standard of care biopsy of residual mass. If initial FDG PET data is not available in DICOM format or is of suboptimal image quality, a repeat FDG PET/CT at the study site may be required.
  • We will accrue 70 participants (40 in the early response arm and 30 in the residual mass arm) to this study.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Participant must be enrolled in a lymphoma therapy study at the NIH Clinical Center OR be enrolled in the CALGB 50303 study at another site OR undergoing a new course of treatment of lymphoma at another facility.

Participants must have a clinical course consistent with lymphoma and have available documentation of lymphoma from either the NCI or from an outside pathology laboratory.

Participant must be 18 years or older.

ECOG Performance score of 0 or 1.

Ability to provide informed consent. All patients must sign a document of informed consent indicating their understanding of the investigational nature and risks of the study before any protocol related studies are performed.

For subjects enrolling in early response arm

  • Must be enrolled in CALGB 50303 or a lymphoma therapy study at the NIH Clinical Center or undergoing a new course of treatment of lymphoma at another facility
  • Must not have begun lymphoma therapy for this tumor occurrence/ relapse
  • Prior completed therapy does NOT affect eligibility

For subjects enrolling in the residual FDG avid mass arm

  • Must have a residual FDG PET positive mass greater than equal to 1cm, with uptake greater than that of mediastinal blood pool.
  • Participant will undergo a repeat FDG PET/CT scan if the original FDG/PET imaging performed at an outside institution is not of adequate imaging quality for subjects enrolling in the residual FDG mass arm.

EXCLUSION CRITERIA:

Known allergy to fluorothymidine.

Participants for whom enrollment would significantly delay (greater than 2 weeks) the scheduled standard of care therapy.

Participants with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results are excluded.

Participants with severe claustrophobia not relieved by oral anxiolytic medication or patients weighing greater than 136 kg (weight limit for scanner table).

Other medical conditions deemed by the PI or associates to make the patient ineligible for protocol procedures.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00775268

Contacts
Contact: Yolanda McKinney, R.N. (301) 443-6913 ymckinney@mail.nih.gov
Contact: Karen A Kurdziel, M.D. (301) 443-0622 kurdziek@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Walter Reed National Medical Center Recruiting
Bethesda, Maryland, United States, 20301
Sponsors and Collaborators
Investigators
Principal Investigator: Karen A Kurdziel, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT00775268     History of Changes
Other Study ID Numbers: 080200, 08-C-0200
Study First Received: October 17, 2008
Last Updated: July 2, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
18F Fluorothymidine
PET/CT
FLT
Lymphoma
FDG

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 21, 2014