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

January 6, 2026 updated by: Mayo Clinic

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

82

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic in Arizona
        • Contact:
        • Principal Investigator:
          • Cecilia Y. Arana Yi, MD
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Recruiting
        • Mayo Clinic in Florida
        • Contact:
        • Principal Investigator:
          • Talha Badar, MD
    • Minnesota
      • Albert Lea, Minnesota, United States, 56007
        • Recruiting
        • Mayo Clinic Health System in Albert Lea
        • Contact:
        • Principal Investigator:
          • Mina S. Hanna, MD
      • Mankato, Minnesota, United States, 56001
        • Recruiting
        • Mayo Clinic Health System-Mankato
        • Contact:
        • Principal Investigator:
          • Amrit B. Singh, MBBS
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:
        • Principal Investigator:
          • Mithun V. Shah, MD, PhD
    • Wisconsin
      • Eau Claire, Wisconsin, United States, 54701
        • Recruiting
        • Mayo Clinic Health System-Eau Claire Clinic
        • Contact:
        • Principal Investigator:
          • Eyad S. Al-Hattab, MD
      • La Crosse, Wisconsin, United States, 54601
        • Recruiting
        • Mayo Clinic Health System-Franciscan Healthcare
        • Contact:
        • Principal Investigator:
          • Scott H. Okuno, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Supportive care (bone marrow aspiration, CFU)
Patients undergo bone marrow aspiration and hair, buccal, 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.
Procedure: Bone Marrow Aspiration
Undergo bone marrow aspiration
Other: Electronic Health Record Review
Ancillary studies
Procedure: Follow-Up
Undergo CFU
Other Names:
  • Active Follow-up
  • Clinical Signs Follow-up
  • CLSFUP
  • Follow Up
  • follow_up
  • Followed
  • Followup
Other: Genetic Counseling
Receive genetic counselor consultation
Other: Genetic Testing
Undergo sequencing analysis
Other Names:
  • Genetic Examination
  • Genetic Test
  • Genetic Analysis
Procedure: Biospecimen Collection
Undergo hair, buccal, and saliva sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Development of myeloid neoplasm post-cytotoxic therapies (MN-pCT)
Time Frame: 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.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Investigators

  • Principal Investigator: Mithun V. Shah, MD, Mayo Clinic in Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 22, 2024

Primary Completion (Estimated)

December 16, 2027

Study Completion (Estimated)

December 16, 2027

Study Registration Dates

First Submitted

October 3, 2024

First Submitted That Met QC Criteria

October 3, 2024

First Posted (Actual)

October 8, 2024

Study Record Updates

Last Update Posted (Actual)

January 8, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MC230818 (Other Identifier: Mayo Clinic)
  • NCI-2024-07738 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • 24-005734 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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