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

Sponsor

Adaptive Biotechnologies (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05255354

Collaborator

Stanford University (Other)

300

Enrollment

Location

Anticipated Duration (Months)

5.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Follicular Lymphoma Diffuse Large B Cell Lymphoma Mantle Cell Lymphoma	Device: ClonoSEQ

Study Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Jun 11, 2022

Anticipated Primary Completion Date :

Sep 11, 2023

Anticipated Study Completion Date :

Mar 11, 2027

Arms and Interventions

Arm	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.

Arm

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Center	Palo Alto	California	United States	94306

Sponsors and Collaborators

Adaptive Biotechnologies
Stanford University

Investigators

Study Director: Heidi Simmons, PhD, Adaptive Biotechnologies

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Adaptive Biotechnologies

ClinicalTrials.gov Identifier:

NCT05255354

Other Study ID Numbers:

ADAP-014
CCT5065

First Posted:

Feb 24, 2022

Last Update Posted:

Apr 20, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Large B-Cell, Diffuse

Study Results

No Results Posted as of Apr 20, 2022