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

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

Status

Recruiting

Phases

Unknown

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06630104

Enrollment

Registered

2024-10-08

Start date

2024-11-22

Completion date

2027-12-16

Last updated

2026-08-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoproliferative Disorder, Multiple Myeloma

Brief 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, saliva, buccal swab, or skin 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 CFU 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.

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

SUPPORTIVE_CARE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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 or skin punch biopsy specimens (skin punch biopsy specimens will be obtained from Mayo Clinic Rochester patients only) for correlative research * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) * Willingness to provide mandatory saliva or buccal swab sample for correlative research

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame	Description
Pathogenic and likely pathogenic germline and somatic variants associated with increased risk	At baseline	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.
Unexplained cytopenia	At day 90	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.

Secondary

Measure	Time frame	Description
Development of myeloid neoplasm post-cytotoxic therapies (MN-pCT)	Up to 2 years	Assessed as development of MN-pCT at any time following CAR-T infusion. MN-pCT is defined per The World Health Organization- Five Well-Being Index (WHO-5). 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.

Countries

United States

Contacts

CONTACTClinical Trials Referral Office

mayocliniccancerstudies@mayo.edu855-776-0015

PRINCIPAL_INVESTIGATORMithun V. Shah, MD

Mayo Clinic in Rochester

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Aug 13, 2026