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

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

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.

Study Overview

• Status: Recruiting
• Conditions: DLBCL
• Intervention / Treatment: Drug: Rituximab Prednisone; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Robin Boerman; Phone Number: 585-273-1507; Email: Robin_Boerman@URMC.Rochester.edu

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester
      • Contact: Andrew Bui

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Baseline PET; R-CHOP

Drug: Rituximab Prednisone; A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma; Drug: Cyclophosphamide; A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma; Drug: Doxorubicin; A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma; Drug: Vincristine; A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma; Drug: Prednisone; A Phase II Study of PET Adapted Therapy and Non-invasive Monitoring for Previously Untreated Limited Stage Diffuse Large B Cell Lymphoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of Rochester
• Investigators: Principal Investigator: Carla Casulo, University of Rochester

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2019
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (Actual): November 29, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Rituximab; Prednisone; Doxorubicin; Vincristine
• Other Study ID Numbers: ULYM18040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes