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Tumor-Specific Clonotype, Metabolic Profile, and PET/CT in Predicting Chemotherapy Response in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

Primary Purpose

Recurrent Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Chemotherapy
Computed Tomography
Fludeoxyglucose F-18
Positron Emission Tomography
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Recurrent Diffuse Large B-Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subject/legal representative willing and able to provide written informed consent
  • Histologically confirmed aggressive B-cell DLBCL, including follicular lymphoma (FL) transforming to DLBCL and high grade B-cell lymphoma
  • Willing to provide existing relapse-confirmatory DLBCL tumor sample
  • Relapsed from or refractory to at least one treatment containing a CD20 monoclonal antibody combined with anthracycline-based chemotherapy
  • CT scans showing involvement of 1 or more clearly demarcated lesions with a long axis > 1.5 cm and short axis >= 1.0 cm
  • Baseline FDG-PET/CT scans must demonstrate at least one hypermetabolic lesion as defined by the Deauville criteria localizing to CT-defined anatomical tumor sites
  • Suitable candidate for therapy with standard salvage chemotherapy and autologous stem cell transplant (ASCT) as determined by the treating physician
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Life expectancy of >= 12 weeks as estimated by the treating physician
  • Negative serum beta-human chorionic gonadotropin (beta-hCG) test (women of childbearing potential only)
  • Hemoglobin >= 8.5 g/dL
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 75,000/mm^3
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 x institutional upper limit of normal (ULN) for cases involving liver metastasis and =< 3 x institutional ULN for all other cases
  • Bilirubin =< 2 x ULN (unless related to lymphoma) or =< 5 x ULN for subjects with documented or suspected Gilbert's disease
  • Serum creatinine =< 1.5 x ULN or calculated creatinine clearance (CrCl) >= 50 mL/min as determined by the Cockcroft-Gault equation

Exclusion Criteria:

  • Any condition that, in the opinion of the investigator, would interfere with the interpretation of study results or subject safety including non-malignant FDG avid diseases such as sarcoidosis or other granulomatous disease
  • Uncontrolled diabetes mellitus
  • Concurrent enrollment in another clinical study where they are receiving non-standard salvage chemotherapy, (i.e., concurrent enrollment is allowable if the patient is receiving standard salvage chemotherapy and research imaging is allowed)
  • Any chemotherapy, radiotherapy, immunotherapy, biologic, or investigational therapy for treatment of lymphoma within 14 days prior to treatment
  • Symptomatic congestive heart failure

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Diagnostic (PET/CT, clonotype, metabolic profile)

Arm Description

Patients receive standard salvage chemotherapy as determined by the treating physician. Patients undergo FDG PET/CT scans at baseline (between days -21 to 0), on day 4 after completion of first high-dose chemotherapy, on day 21 after completion of the first course of chemotherapy, and on day 42 after the end of the second course of chemotherapy. Blood samples are also collected for tumor-specific clonotype and metabolic profile at baseline (days -5 to 0) and on days 4, 8, 21, and 42.

Outcomes

Primary Outcome Measures

Response to therapy
Defined as demonstrating the chemotherapy-sensitiveness for curative autologous stem cell transplant (ASCT) based on fludeoxyglucose F 18 FDG positron emission tomography (PET)/computed tomography (CT) results. Non-responders will be classified as having equivocal active disease with a positive biopsy for confirmation and unequivocal active disease in a previously biopsy-confirmed site of disease. Descriptive statistics will be used to summarize the demographic and clinical characteristics of patients. The concordance rate between the interim PET/CT scans and the final FDG PET/CT scan, and its 95% confidence interval, will be reported. The change in drug of choice (DoC) and metabolic profile tests will be explored using mixed effect linear regression models.

Secondary Outcome Measures

Response rate (RR)
RR will be analyzed using multivariate logistic regression.
Progression-free survival
The association between FDG PET/CT scans, DoC and metabolic profile tests, and the progression-free from primary treatment failure will be examined using a stratified Cox regression model.
Overall survival (OS)
The association between FDG PET/CT scans, DoC and metabolic profile tests, and the OS from primary treatment failure will be examined using a stratified Cox regression model.

Full Information

First Posted
March 27, 2015
Last Updated
October 27, 2022
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02405078
Brief Title
Tumor-Specific Clonotype, Metabolic Profile, and PET/CT in Predicting Chemotherapy Response in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
Official Title
Pilot Project for Creation of the DLBCL Response Prediction Model: Combining Early Interim Functional Imaging, Detection of a Tumor-Specific Clonotype and Metabolic Profiling of Blood of in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma to Predict Response to Standard Immunochemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
October 13, 2015 (Actual)
Primary Completion Date
October 3, 2022 (Actual)
Study Completion Date
October 3, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This pilot clinical trial studies tumor-specific markers (clonotype), blood tests, and positron emission tomography (PET)/computed tomography (CT) in predicting treatment response at different times during chemotherapy in patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Studying samples of blood in the laboratory from patients during chemotherapy may help doctors learn more about the effects of treatment on cells and may help doctors determine whether patients are responding to treatment. PET/CT scan procedures are done at the same time with the same machine and the combined scans give more detailed pictures of areas inside the body than either scan gives by itself and may help doctors find out how well treatment is working.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the ability of blood based detection of a tumor-specific clonotype and metabolic profiling and functional imaging to predict response to standard immunochemotherapy. SECONDARY OBJECTIVES: I. To evaluate the optimal time points to create the diffuse large B-cell lymphoma (DLBCL) response prediction model. TERTIARY OBJECTIVES: I. To evaluate the prognostic value of clinical factors, cell of origin subtype, and circulating immune cell subsets for response to therapy. II. To evaluate for novel genomic aberrations or signatures which correlate with therapeutic failure. III. To evaluate the ability of additional positron emission tomography (PET)/computed tomography (CT) imaging interpretation techniques to correlate with clinical outcomes. IV. To evaluate the correlation of blood-based detection of clonotype with fludeoxyglucose F-18 (FDG) PET/CT disease assessment. V. To evaluate the utility of alternative methods of minimal residual disease detection. VI. To evaluate measurement of circulating metabolic profiling with imaging results and clinical outcomes. OUTLINE: Patients receive standard salvage chemotherapy as determined by the treating physician. Patients undergo FDG PET/CT scans at baseline (between days -21 to 0), on day 4 after completion of first high-dose chemotherapy, on day 21 after completion of the first course of chemotherapy, and on day 42 after the end of the second course of chemotherapy. Blood samples are also collected for tumor-specific clonotype and metabolic profile at baseline (days -5 to 0) and on days 4, 8, 21, and 42.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Diagnostic (PET/CT, clonotype, metabolic profile)
Arm Type
Experimental
Arm Description
Patients receive standard salvage chemotherapy as determined by the treating physician. Patients undergo FDG PET/CT scans at baseline (between days -21 to 0), on day 4 after completion of first high-dose chemotherapy, on day 21 after completion of the first course of chemotherapy, and on day 42 after the end of the second course of chemotherapy. Blood samples are also collected for tumor-specific clonotype and metabolic profile at baseline (days -5 to 0) and on days 4, 8, 21, and 42.
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Other Intervention Name(s)
Chemo, Chemotherapy (NOS), Chemotherapy, Cancer, General
Intervention Description
Given standard salvage chemotherapy
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computerized Axial Tomography, computerized tomography, CT, CT SCAN, tomography
Intervention Description
Undergo FDG-PET/CT scan
Intervention Type
Drug
Intervention Name(s)
Fludeoxyglucose F-18
Other Intervention Name(s)
18FDG, FDG, fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18
Intervention Description
Undergo FDG-PET/CT scan
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging
Intervention Description
Undergo FDG-PET/CT scan
Primary Outcome Measure Information:
Title
Response to therapy
Description
Defined as demonstrating the chemotherapy-sensitiveness for curative autologous stem cell transplant (ASCT) based on fludeoxyglucose F 18 FDG positron emission tomography (PET)/computed tomography (CT) results. Non-responders will be classified as having equivocal active disease with a positive biopsy for confirmation and unequivocal active disease in a previously biopsy-confirmed site of disease. Descriptive statistics will be used to summarize the demographic and clinical characteristics of patients. The concordance rate between the interim PET/CT scans and the final FDG PET/CT scan, and its 95% confidence interval, will be reported. The change in drug of choice (DoC) and metabolic profile tests will be explored using mixed effect linear regression models.
Time Frame
Up to 42 days
Secondary Outcome Measure Information:
Title
Response rate (RR)
Description
RR will be analyzed using multivariate logistic regression.
Time Frame
Up to 18 months
Title
Progression-free survival
Description
The association between FDG PET/CT scans, DoC and metabolic profile tests, and the progression-free from primary treatment failure will be examined using a stratified Cox regression model.
Time Frame
Up to 18 months
Title
Overall survival (OS)
Description
The association between FDG PET/CT scans, DoC and metabolic profile tests, and the OS from primary treatment failure will be examined using a stratified Cox regression model.
Time Frame
Up to 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject/legal representative willing and able to provide written informed consent Histologically confirmed aggressive B-cell DLBCL, including follicular lymphoma (FL) transforming to DLBCL and high grade B-cell lymphoma Willing to provide existing relapse-confirmatory DLBCL tumor sample Relapsed from or refractory to at least one treatment containing a CD20 monoclonal antibody combined with anthracycline-based chemotherapy CT scans showing involvement of 1 or more clearly demarcated lesions with a long axis > 1.5 cm and short axis >= 1.0 cm Baseline FDG-PET/CT scans must demonstrate at least one hypermetabolic lesion as defined by the Deauville criteria localizing to CT-defined anatomical tumor sites Suitable candidate for therapy with standard salvage chemotherapy and autologous stem cell transplant (ASCT) as determined by the treating physician Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Life expectancy of >= 12 weeks as estimated by the treating physician Negative serum beta-human chorionic gonadotropin (beta-hCG) test (women of childbearing potential only) Hemoglobin >= 8.5 g/dL Absolute neutrophil count (ANC) >= 1500/mm^3 Platelet count >= 75,000/mm^3 Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 x institutional upper limit of normal (ULN) for cases involving liver metastasis and =< 3 x institutional ULN for all other cases Bilirubin =< 2 x ULN (unless related to lymphoma) or =< 5 x ULN for subjects with documented or suspected Gilbert's disease Serum creatinine =< 1.5 x ULN or calculated creatinine clearance (CrCl) >= 50 mL/min as determined by the Cockcroft-Gault equation Exclusion Criteria: Any condition that, in the opinion of the investigator, would interfere with the interpretation of study results or subject safety including non-malignant FDG avid diseases such as sarcoidosis or other granulomatous disease Uncontrolled diabetes mellitus Concurrent enrollment in another clinical study where they are receiving non-standard salvage chemotherapy, (i.e., concurrent enrollment is allowable if the patient is receiving standard salvage chemotherapy and research imaging is allowed) Any chemotherapy, radiotherapy, immunotherapy, biologic, or investigational therapy for treatment of lymphoma within 14 days prior to treatment Symptomatic congestive heart failure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason Westin
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34435552
Citation
Cherng HJ, Chuang HH, Steiner R, Fayad L, Strati P, Nair R, Hagemeister F, Nastoupil LJ, Lee HJ, Neelapu SS, Flowers CR, Samaniego F, Rodriguez M, Macapinlac HA, Feng L, Westin J. A prospective study on early PET/CT scans during the first cycle of salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2022 Jan;63(1):74-83. doi: 10.1080/10428194.2021.1971223. Epub 2021 Aug 26.
Results Reference
derived
Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website

Learn more about this trial

Tumor-Specific Clonotype, Metabolic Profile, and PET/CT in Predicting Chemotherapy Response in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

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