Understanding the Mechanisms of Clonal and Non-clonal Cytopenia Following CAR-T Therapy for Multiple Myeloma or CD19+ Lymphoproliferative Disorder (LPD)

Mayo Clinic

Status

Enrolling

Conditions

Multiple Myeloma

Lymphoproliferative Disorder

Treatments

Other: Genetic Testing

Procedure: Bone Marrow Aspiration

Other: Electronic Health Record Review

Other: Genetic Counseling

Procedure: Biospecimen Collection

Procedure: Follow-Up

Study type

Interventional

Funder types

Other

Identifiers

NCT06630104

MC230818 (Other Identifier)

24-005734 (Other Identifier)

NCI-2024-07738 (Registry Identifier)

Details and patient eligibility

About

This clinical trial evaluates the impact of preexisting and therapy-emergent germline and somatic variants on cytopenia in patients with multiple myeloma or CD19 positive lymphoproliferative disorder (LPD) following chimeric antigen receptor T-cell (CAR-T) therapy. The most common adverse event after CAR-T therapy is lower than normal blood cells (cytopenia) and up to one third of patients experience cytopenia that last longer than 30 days post-infusion. Germline and somatic variants are changes in genes found using cancer genomic tests. Cancer genetic/genomic testing is a series of tests that find specific changes in cancer cells or in blood deoxyribonucleic acid. Identifying gene mutations may help identify the risk of cytopenia in patients with multiple myeloma or CD19 positive LPD following CAR-T therapy.

Full description

PRIMARY OBJECTIVE:

I. Determine the preexisting and therapy-emergent germline and somatic variants associated with an increased risk of clonal and non-clonal cytopenia following CAR-T cell therapy on research basis.

SECONDARY OBJECTIVE:

I. Characterize the baseline transcriptomic signature associated with non-clonal and clonal cytopenia following CAR-T therapy on research basis.

OUTLINE:

Patients undergo bone marrow aspiration and hair, buccal, and saliva sample collection up to 14 days prior to lymphodepleting (LD) therapy. Patients undergo clinical follow-up (CFU) on day 90 post-CAR-T therapy. Patients with unexplained cytopenia also undergo bone marrow aspiration for sequencing analysis on day 90 and at development of myeloid neoplasm post-cytotoxic therapies (MN-pCT) during CFU. Patients also undergo bone marrow aspiration at determination of clonal evolution or myeloid neoplasm if not done during on day 90.

Patients with unexplained cytopenia at day 90 are followed up every 90 days for up to 2 years until resolution. Patients without unexplained cytopenia are followed clinically for up to 2 years.

Enrollment

82 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age ≥ 18 years
Histologically or cytologically confirmed diagnosis of multiple myeloma (MM) as defined in International Myeloma Working Group (IMWG) criteria or a CD19+ lymphoproliferative disorder (LPD) as defined by 2016 World Health Organization (WHO) classification
Provide written informed consent
Willingness to provide mandatory bone marrow aspirate specimens for correlative research. All bone marrow aspirate samples are collected during a clinical procedure
Willingness to provide mandatory hair follicle specimens for correlative research
Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
Willingness to provide saliva and buccal samples for research

Exclusion criteria

Ineligible for CAR-T therapy
Patients diagnosed with myeloid neoplasm before CAR-T therapy

Trial design

Primary purpose

Supportive Care

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

82 participants in 1 patient group

Supportive care (bone marrow aspiration, CFU)

Experimental group

Description: