Optimizing ctDNA-based MRD Assessment in DLBCL, MCL, and FL Patients Undergoing CAR Therapy

In this study, invesigators propose to analyze 150 DLBCL patients, 50 MCL patients, and 100 FL patients to determine the clinical utility of ctDNA- as well as circulating tumor cell (CTC)-based MRD assessment in CAR therapy patients. The project detailed in this protocol will utilize the clonoSEQ platform as specific quantification of residual DLBCL/FL/MCL and correlate its results with radiologic assessment of disease and clinical outcomes. Invesitgators predict there will be a strong correlation between ctDNA and PET/CT and dynamic changes in ctDNA will precede radiologic evidence of disease recurrence in patients following CAR therapy.

Study Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; Mantle Cell Lymphoma; Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Device: ClonoSEQ

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Heidi Simmons, PhD; Phone Number: 206-279-2591; Email: hsimmons@adaptivebiotech.com
• Study Contact Backup: Name: Monica Gallucci; Email: mgallucci@adaptivebiotech.com

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94306
      • Recruiting
      • Stanford Cancer Center
      • Contact: Paul Hanson; Email: hansonpj@stanford.edu
      • Principal Investigator: David Miklos, MD, PhD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Subjects ≥ 18 years of age, with DLBCL, FL, or MCL who are undergoing standard-of-care CAR therapy.

Description

Inclusion Criteria:

• Immunophenotypically confirmed diagnosis of follicular lymphoma (FL), Immunophenotypically confirmed diagnosis of Large B Cell Lymphoma (LBCL) (including transformed FL and Primary Mediastinal B-cell Lymphoma) OR Immunophenotypically confirmed diagnosis of mantle cell lymphoma (MCL) undergoing commercially approved CAR-T therapy in accordance with FDA indication with enrollment in this trial prior to CAR infusion
• CAR-T product must meet manufacturer specifications
• PET measurable disease at the time a decision is made to prescribe CAR treatment
• Has sample from diagnosis or relapse available for genomic DNA extraction to identify patient's clonotype via clonoSEQ (see lab manual for details)

Exclusion Criteria:

• Lack of archival diagnostic or fresh/archival relapse tissue for purposes of determining patient's lymphoma clonotype. Given that 5-10% of patients cannot have a clonotype identified by clonoSEQ, those patients will be removed from the study and excluded from analysis, but their samples will continued to be stored for future analysis as improvements to the analysis platform are made.
• No patients are to be excluded on the basis of gender, race, ethnic background, sexual orientation, or other demographic characteristics.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Diffuse Large B Cell Lymphoma; For DLBCL patients, prospective blood samples will be collected, in provided collection kits, at: pre-lymphodepletion chemotherapy, Day+14, Day+28, Day+90, Day+180, and potentially at relapse following CAR infusion. For DLBCL, PET/CT scan images done prior to CAR19 therapy, Day 28 post-infusion, 3 months post-infusion, and 6 months post-infusion of CAR19 cells	Device: ClonoSEQ; Cancer clonotype sequences are identified in diagnostic 'ID' samples and then sequence frequencies are measured in follow up samples.
Follicular Lymphoma; For FL patients, prospective blood samples will be collected, in provided collection kits, at: pre-lymphodepletion chemotherapy, Day+14, Day+28, Day+90, Day+180, Day+365, and potentially D+547 and at relapse following CAR infusion. For FL patients, PET/CT scan images done prior to CAR19 therapy, Day 28 post-infusion, 3 months post-infusion, and 6 months post-infusion of CAR19 cells	Device: ClonoSEQ; Cancer clonotype sequences are identified in diagnostic 'ID' samples and then sequence frequencies are measured in follow up samples.
Mantle Cell Lymphoma; For MCL patients, prospective blood samples will be collected, in provided collection kits, at: pre-lymphodepletion chemotherapy, Day+14, Day+28, Day+90, Day+180, Day+365, and potentially D+547 and at relapse following CAR infusion. For MCL patients, PET/CT scan images done prior to CAR19 therapy, Day 28 post-infusion, 3 months post-infusion, and 6 months post-infusion of CAR19 cells	Device: ClonoSEQ; Cancer clonotype sequences are identified in diagnostic 'ID' samples and then sequence frequencies are measured in follow up samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome: Predicting Progression Free Survival	Ability of ctDNA MRD assessment to predict progression-free survival (PFS) at 6 months following CAR infusion in DLBCL, FL and MCL patients.	0-18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Objective: Correlation of minimal residual disease and tumor burden	-Determine the correlation between quantified MRD and metabolic tumor volume (MTV)	0-18 months
Secondary Objective continued: Looking at clinical information of minimal residual disease	-Determine the clinical utility of MRD assessments in an exploratory analysis	0-18 months
Secondary Objective continued: Additional correlations	-Determine the correlation between ctDNA-based and CTC-based MRD assessments in DLBCL/FL/MCL	0-18 months

Collaborators and Investigators

• Sponsor: Adaptive Biotechnologies
• Collaborators: Stanford University
• Investigators: Study Director: Heidi Simmons, PhD, Adaptive Biotechnologies

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 9, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): February 24, 2022

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 21, 2024
• Last Verified: August 1, 2024

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, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell
• Other Study ID Numbers: ADAP-014; CCT5065 (Other Identifier: Stanford Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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