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

Not Applicable

Recruiting

• Conditions: Lymphoproliferative Disorder; Multiple Myeloma
• Interventions: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Other: Electronic Health Record Review; Procedure: Follow-Up; Other: Genetic Counseling; Other: Genetic Testing

• Registration Number: NCT06630104
• Lead Sponsor: Mayo Clinic

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.

SECONDARY OBJECTIVE:

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

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. Additionally, patients a receive genetic counselor consultation on study.

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.

Study Timeline

• Study First Submitted: 2024-10-03
• Study First Submitted QC: 2024-10-03
• Study First Posted: 2024-10-08
• Study Start: 2024-11-22
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-18
• Last Update Posted: 2025-04-23
• Primary Completion: 2025-12-16
• Study Completion: 2025-12-16

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 82

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Supportive care (bone marrow aspiration, CFU)	Electronic Health Record Review	Patients undergo bone marrow aspiration and hair and saliva sample collection up to 14 days prior to LD therapy. Patients undergo 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 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. Additionally, patients receive a genetic counselor consultation on study.
Supportive care (bone marrow aspiration, CFU)	Biospecimen Collection	Patients undergo bone marrow aspiration and hair and saliva sample collection up to 14 days prior to LD therapy. Patients undergo 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 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. Additionally, patients receive a genetic counselor consultation on study.
Supportive care (bone marrow aspiration, CFU)	Bone Marrow Aspiration	Patients undergo bone marrow aspiration and hair and saliva sample collection up to 14 days prior to LD therapy. Patients undergo 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 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. Additionally, patients receive a genetic counselor consultation on study.
Supportive care (bone marrow aspiration, CFU)	Follow-Up	Patients undergo bone marrow aspiration and hair and saliva sample collection up to 14 days prior to LD therapy. Patients undergo 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 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. Additionally, patients receive a genetic counselor consultation on study.
Supportive care (bone marrow aspiration, CFU)	Genetic Counseling	Patients undergo bone marrow aspiration and hair and saliva sample collection up to 14 days prior to LD therapy. Patients undergo 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 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. Additionally, patients receive a genetic counselor consultation on study.
Supportive care (bone marrow aspiration, CFU)	Genetic Testing	Patients undergo bone marrow aspiration and hair and saliva sample collection up to 14 days prior to LD therapy. Patients undergo 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 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. Additionally, patients receive a genetic counselor consultation on study.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (7)

Mayo Clinic in Arizona; 🇺🇸 Scottsdale, Arizona, United States

Mayo Clinic in Florida; 🇺🇸 Jacksonville, Florida, United States

Mayo Clinic Health System in Albert Lea; 🇺🇸 Albert Lea, Minnesota, United States

Mayo Clinic Health System-Mankato; 🇺🇸 Mankato, Minnesota, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States

Mayo Clinic Health System-Eau Claire Clinic; 🇺🇸 Eau Claire, Wisconsin, United States

Mayo Clinic Health System-Franciscan Healthcare; 🇺🇸 La Crosse, Wisconsin, United States