A Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma

Study Overview
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Brief Summary
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The overarching goals of this study are to measure levels of circulating tumor DNA (ctDNA) in patients with early stage diffuse large B cell lymphoma (DLBCL), to assess the change in ctDNA during treatment in order to prospectively identify markers of treatment failure, and to use ctDNA as a future tool for response adapted therapy.

Detailed Description
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The long-term objective of this proposal is to determine the correlation between FDG-PET and MRD, as measured by ctDNA in patients with early stage DLBLC. Patients will be treated with standard chemoimmunotherapy and radiation based on the recently completed SWOG S1001 study, however no radioimmunotherapy will be used (NCT01359592). Response to treatment will be determined by contemporary Deauville criteria. Assessment of ctDNA (non-invasive disease monitoring) will be determined at diagnosis and will continue at pre-defined specific time points after therapy is complete.

Official Title
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A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma

Conditions
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DLBCL

Intervention / Treatment
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* Drug: Rituximab Prednisone
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated limited stage non bulky DLBCL; defined as limited stage by routine staging criteria in lymphoma involving FDG-PET and bone marrow biopsies (the Lugano criteria)[21] Patients with grade 3B follicular lymphoma and transformed indolent lymphoma are included Ages ≥ 18 Measurable disease, assessable by radiographic examination with FDG-PET showing involvement Access to archived or fresh/frozen tumor biopsies No uncontrolled medical comorbidities Adequate cardiac function (EF > or equal to 50%), no unstable angina Adequate renal function (GFR > 60) Adequate liver function (liver function tests should be no greater than 2 x upper limit of normal) including normal bilirubin levels, no greater than 2 x upper limit of normal unless patient has a history of Gilbert's disease Adequate marrow reserves as indicated by complete blood count in the judgment of the treating investigator Exclusion Criteria: Pregnancy, positive serum HCG within 28 days of enrollment, or breast-feeding Bulky disease greater than 10 cm in any dimension

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Baseline PET<br>R-CHOP | Drug: Rituximab Prednisone<br>* A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma<br>Drug: Cyclophosphamide<br>* A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma<br>Drug: Doxorubicin<br>* A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma<br>Drug: Vincristine<br>* A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma<br>Drug: Prednisone<br>* A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between fluorodeoxyglucose positron emission tomography (FDG-PET) and MRD, as measured by circulating tumor plasma DNA (ctDNA) in patients with early stage diffuse large B cell lymphoma (DLBCL). |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET CR rate |  | 5 years | 
| Change in minimal residual disease (MRD) from baseline to time of re-staging PET |  | 5 years | 
| Re-staging Deauville score of 1, 2, or 3 (negative PET scan) |  | 5 years | 
| Following 3 cycles of R-CHOP, if PET scan demonstrates complete response, defined by Deauville score of 1, 2, or 3 (negative PET scan), radiation therapy will not be required moving forward |  | 5 years | 
| Toxicity rates using CTCAE v4.03 |  | 5 years | 
| Changes in quality of life using PROMIS scale 10 scale will be administered to patients at the time of diagnosis, at the conclusion of all therapy, and at 12 month intervals |  | 5 years | 
| Overall survival (OS) of patients through two years of follow-up. |  | Patients will be assessed by physical exam and routine bloodwork every 3 months in the 1st year after conclusion of treatment, and every 6 months in the second year following treatment. They will be assessed yearly during years 3, 4 and 5. | 
| Progression free survival (PFS) |  | From time of baseline scan through two years of follow-up |