Study to Assess for Measurable Residual Disease (MRD) in Multiple Myeloma Patients

Multiple Myeloma Clinical Trial

Official title:

A Multimodality Approach to Minimal Residual Disease Detection to Guide Post-Transplant Maintenance Therapy in Multiple Myeloma (MRD2STOP)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04108624
• Other study ID #: IRB19-0339
• Status: Recruiting
• Phase: N/A
• Start date: October 30, 2019
• Est. completion date: July 1, 2025

Study information

• Verified date: January 2024
• Source: University of Chicago
• Contact: Andrzej Jakubowiak, MD
• Phone: 773-834-1592
• Email: ajakubowiak[@]medicine.bsd.uchicago.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to assess for Measurable Residual Disease (MRD) in multiple myeloma at a deeper level than what is currently available by combining novel imaging and laboratory techniques, determine if patients who are MRD-negative by these multiple modalities can safely and effectively discontinue post-transplant maintenance therapy, and determine if liquid biopsies is a more accurate and/or less invasive sampling technique for multiple myeloma.

The purpose of this research is to determine if patients who are MRD-negative by multiple modalities ("multimodality MRD-negative") can safely and effectively discontinue post-transplant maintenance therapy (single agent lenalidomide, pomalidomide, bortezomib, or ixazomib) after receiving at least one year of maintenance therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: July 1, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Males and females > 18 years of age

• ECOG performance status less than or equal to 2 (Karnofsky > 60%)

• Patients with a diagnosis of multiple myeloma who have undergone initial treatment, with or without autologous stem cell transplant, and currently treated with single-agent maintenance therapy (lenalidomide, pomalidomide, bortezomib, daratumumab, or ixazomib) for a duration of at least 1 year. The 1 year duration can include time spent receiving at least 8 cycles of doublet or triplet induction regimens OR multi-agent post-transplant maintenance prior to conversion to single agent maintenance therapy.

• Patients must have had their most recent bone marrow testing within the last 2 years and negative for MRD by flow cytometry (with a sensitivity of at least 10-5) or by NGS with a sensitivity of at least 10-5.

• Patients must have achieved a CR (CR) by IMWG consensus response criteria. For patients with a persistent low level paraprotein ('M-spike'), mass spectrometry may be used to determine if the paraprotein is significant or not. Results of mass spectrometry may be used to supercede results of serum protein electrophoresis.

• Patients must have a most recent PET/CT within the last 1.5 years without evidence of myeloma disease.

• Must have baseline bone marrow sample that can be used for clonality identification for NGS and mass spectrometry if not already performed.

• Willing and able to undergo a bone marrow biopsy and aspiration.

• Ability to understand and the willingness to sign a written informed consent document.

• Females of childbearing potential (FCBP) must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) if continued on lenalidomide as part of standard of care and 2) for at least 28 days after discontinuation of lenalidomide

• All participants in the US must have already been consented to and registered into the mandatory Revlimid REMS® program and be willing and able to comply with the requirements of Revlimid REMS®.

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the intervention are eligible for this trial.

Exclusion Criteria:

• Progressive disease as determined per IMWG consensus response criteria.

• Have not met the criteria for CR by IMWG consensus response criteria.

• MRD-positive disease by flow cytometry, NGS (1 in 1,000,000 cells), or PCR.

• Concomitant hematologic malignancy.

• Known or suspected amyloidosis.

• Unwilling to undergo a bone marrow biopsy.

• Unwilling to discontinue maintenance therapy.

• Any clinically significant medical disease or condition that, in the Treating Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Other:
• Screening Phase
This will identify subjects who are MRD (minimal residual disease) negative and eligible for the discontinuation phase.

Device:
• Discontinuation Phase
Patients will undergo discontinuation of their maintenance therapy if they are MRD negative by PET/CT (Positron Emission Tomography/Computed Tomography), flow cytometry and next generation sequencing

Locations

Country	Name	City	State
United States	University Of Chicago Medicine Comprehensive Cancer Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the MRD conversion rate	Determine the MRD conversion rate from 1 in 1,000,000 cells and 1 in 10,000,000 cells negative to positive after discontinuation of maintenance therapy.	3 years
Primary	Median Progression Free Survival rate	Assess progression free survival of double MRD-negative (1 in 1,000,000 cells negative/1 in 10,000,000 cells negative) patients and of the 1 in 1,000,000 cells negative/1 in 10,000,000 cells positive patients who have discontinued maintenance therapy	3 years
Primary	Median overall survival rate	Assess overall survival of double MRD-negative (1 in 1,000,000 cells negative/1 in 10,000,000 cells negative) patients and of the 1 in 1,000,000 cells negative/1 in 10,000,000 cells positive patients who have discontinued maintenance therapy.	3 years
Secondary	NGS-based Minimal Residual Disease testing determined by the ClonoSeq assay	Determine the feasibility of performing NGS-based MRD testing of bone marrow aspirate samples that have undergone CD138+ immunomagnetic cell separation (i.e. 1 in 10,000,000 cells depth) will be determined by the rate of achieving 20 million cells in raw aspirate sample with a sufficient DNA for analysis as determined by the ClonoSeq assay.	3 years
Secondary	Determine the difference in MRD detection by NGS	Determine the difference in MRD detection by NGS in the bone marrow at depths of 1 in 1,000,000 cells and 1 in 10,000,000 cells.	3 years