RecruitingInterventional

MC230818 Understanding the Mechanisms of Clonal and Non-Clonal Cytopenia Following CAR-T Therapy

NCT ID: NCT06630104Sponsor: Mayo ClinicLast updated: 2026-01-08

Summary

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.

Detailed 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.

Arms & interventions

ProcedureBiospecimen Collection
Undergo hair, buccal, and saliva sample collection
ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
OtherElectronic Health Record Review
Ancillary studies
ProcedureFollow-Up
Undergo CFU
OtherGenetic Counseling
Receive genetic counselor consultation
OtherGenetic Testing
Undergo sequencing analysis

Outcome measures

Primary

Pathogenic and likely pathogenic germline and somatic variants associated with increased risk
The count and percentage of patients with the presence of somatic or germline variants will be reported. The number, type, and function of somatic variants will also be reported.
Time frame: At baseline
Unexplained cytopenia
Unexplained cytopenia will be defined per World Health Organization (WHO)-5 as a combination of any of the following: hemoglobin \< 12 g/dL in females, hemoglobin \< 13 g/dL in males, absolute neutrophil count \< 1.8 x 10\^9/L and platelets \< 150 x 10\^9/L. Logistic regression will be used to identify the presence or absence of baseline germline and somatic mutations associated with unexplained cytopenia. An odds ratio and 95% confidence interval will be reported.
Time frame: At day 90

Secondary

Development of myeloid neoplasm post-cytotoxic therapies (MN-pCT)
Time frame: Up to 2 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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