Real World Observational Study Using Clonoseq® Next Generation Sequencing in Hematologic Malignancies: The 'Watch' Registry

Background:

Clinical response data from trials of investigational agents performed over the past several years in various B-cell malignancies has demonstrated significant improvements in the treatment of these diseases. Despite greatly improved overall response rates, a subset of patients relapses in the short-term while others enjoy prolonged disease-free intervals. These short-term relapses are attributable to residual tumor cells after treatment, but at levels too low for detection by standard clinical assessments. Minimal residual disease (MRD) has emerged as a highly sensitive response assessment tool to measure tumor cells present at a level of 1:10,000 cells or lower via a variety of technologies and platforms. The clonoSEQ® Assay has been cleared by the Food and Drug Administration to detect MRD in the bone marrow of patients with acute lymphoblastic leukemia (ALL) and multiple myeloma (MM) and in either blood or bone marrow for patients with chronic lymphocytic leukemia (CLL). The clonoSEQ Assay can also be used as a laboratory developed test (LDT) to detect MRD in other B-cell malignancies including non-Hodgkin lymphoma (NHL) and in additional sample types such as blood and plasma.

Methods:

The clonoSEQ Assay utilizes multiplex polymerase chain reaction (PCR) and next generation sequencing (NGS) to identify frequency and distribution of clonal sequences associated with a malignant lymphocyte population in an individual patient sample. The principle of this assay is based on the identification of rearranged IgH (VDJ), IgH (DJ), IgK, and IgL receptor gene sequences, as well as translocated BCL1/IgH (J) and BCL2/IgH (J) sequences. The sensitivity of the assay is < 1:1,000,000 when provided sufficient sample input.

The Watch Registry is a prospective, multicenter observational study being conducted in the U.S. and is collecting data from health care providers who use the clonoSEQ Assay as part of routine clinical practice for their patients with ALL, MM, CLL, and NHL. Data collection is focused on the rationale for clonoSEQ Assay use and the subsequent treatment decisions by participating investigators in order to better understand the implementation and impact of this assay in the standard care of hematologic malignancies. The Watch Registry will also evaluate changing practice patterns over a period of at least 3 years.

Patients are eligible if they are ³ 18 years old, have been diagnosed with NHL, MM, ALL, or CLL, are not simultaneously enrolled in an interventional clinical study, and their treating physician is currently or will be using clonoSEQ to monitor their disease burden over the course of the study. Patients may be in any phase of treatment at the time of enrollment. Planned enrollment is 528 patients in order to achieve a target of 476 who have their initial baseline sample plus at least one MRD tracking sample during the course of the study.

The study will collect data on an ongoing basis for approximately 3 years in order to longitudinally understand the utilization of the clonoSEQ Assay and the impact this MRD assessment tool has on clinical care. The primary endpoint of the study is the assessment of the physicians' rationale for MRD testing with clonoSEQ, and the secondary endpoint is the assessment of how those MRD results inform and impact treatment decisions. For each clonoSEQ MRD test ordered, an eCRF questionnaire will capture the rationale for that order (e.g., patient is at end of induction, post-hematopoietic cell transplantation (HCT), monitoring during maintenance, etc) as well as any decisions made regarding patient treatment based upon those results (e.g., patient moved to maintenance therapy, patient will undergo HCT, next line of therapy initiated, etc). Changes in therapeutic regimens will be captured for each patient whether or not those changes are made based upon clonoSEQ results.

The Watch Registry is anticipated to begin enrollment in Q3 2020. A ClinicalTrials.gov post will be submitted prior to study opening.