Free From Maintenance Drug Therapy in Multiple Myeloma (The FREEDMM Trial) for Minimal Residual Disease (MRD (HEME-20)

Free From Maintenance Drug Therapy in Multiple Myeloma (The FREEDMM Trial): A Pilot Study of Minimal Residual Disease (MRD)-Driven Discontinuation of Maintenance (HEME-20)

A pilot study to assess the risk of progression after stopping post-autologous stem cell transplant (ASCT) maintenance therapy in Minimal Residual Disease (MRD)-negative MM patients.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Other: Discontinue maintenance therapy SOC

Detailed Description

This is a pilot study to assess the risk of progression after stopping post-autologous stem cell transplant (ASCT) maintenance therapy in Minimal Residual Disease (MRD)-negative Multiple Myeloma (MM) patients. Patients will be eligible if they have a diagnosis of active MM, have completed at least 2 years of maintenance therapy post-ASCT, and meet International Myeloma Working Group (IMWG) criteria for very good partial response (VGPR) or complete response (CR). Once eligibility is confirmed and informed consent is signed, MRD testing will be performed on routine bone marrow aspirate using standard of care next-generation sequencing (NGS) testing and will be defined at a threshold of 10-6. Patients who are in VGPR or CR and sustained MRD (defined as MRD-negative at two time points that are at least 1 year apart) will go on to discontinue maintenance therapy. MRD-positive patients will continue to be treated as per standard of care (i.e., continue maintenance). Both MRD-positive and MRD-negative patients will be followed as per standard of care for progression using IMWG criteria and for MRD. Quality of life will be assessed at baseline and at 3 months after discontinuing maintenance therapy in MRD-negative patients and at baseline and at the time of next follow-up after MRD testing in MRD-positive patients. In patients who stop maintenance therapy, MRD status will be re-assessed by yearly bone marrow aspirate as per standard of care. Treatment for relapsed/ refractory myeloma will be instituted at the treating physician's discretion for documented clinical and/or biochemical progression. For all patients, a 5-mL peripheral blood and bone marrow sample will be collected and stored at the time of each standard of care bone marrow biopsy and at time of documented disease progression for correlative testing.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Karen Sweiss, PharmD; Phone Number: 312-996-0875; Email: KSweis2@UIC.EDU

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois Cancer Center
      • Contact: Karen Sweiss, PharmD; Phone Number: 312-996-0875; Email: KSweis2@UIC.EDU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ECOG Performance Status equal to or less than 2 within 30 days prior to registration
• Revised International Staging System (R-ISS) I,2 or 3
• Patients with multiple myeloma as defined by IMWG
• Received at least 2 years of post ASCT maintenance (patients may have received any number of prior lines of therapy).
• Maintenance therapy is defined as any anti-myeloma therapy initiated after ASCT to prevent disease recurrence and prolong time in remission (i.e., lenalidomide, bortezomib, RVD, etc.)
• Disease response is VGPR or CR at the time of enrollment as defined by IMWG criteria.
• Patients or their legally authorized representative must be able to understand and be willing to sign a voluntary informed consent form and agree to compliance with the protocol schedule; with the knowledge that they may withdraw consent at any time without impact on future medical care

Exclusion Criteria:

• Patients with plasma cell leukemia, AL amyloidosis or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin (POEMS) syndrome
• Prior organ transplant or condition requiring immunosuppressive therapy
• Prior allogeneic hematopoietic cell transplant
• Treatment with any investigational drug within 30 days prior to enrollment
• Unable to sign an informed consent or their legally authorized represnetative

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Bone marrow MRD-negative VGPR or CR; Discontinue maintenance therapy after at least three years	Other: Discontinue maintenance therapy SOC; Continue maintenance therapy SOC
Other: Bone marrow MRD-positive VGPR or CR; Continue maintenance therapy as per SOC	Other: Discontinue maintenance therapy SOC; Continue maintenance therapy SOC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants that have a sustained MRD-negative VGPR or CR measured by a bone marrow biopsy	Number of participants that have a sustained MRD-negative VGPR or CR measured by a bone marrow biopsy (MRD defined as 10-6)	12 months after stopping maintenance therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants that have a sustained MRD-negative VGPR or CR measured by a bone marrow biopsy	Number of participants that have a sustained MRD-negative VGPR or CR measured by a bone marrow biopsy (MRD defined as 10-6)	2 years after stopping maintenance therapy
Number of participants that relapse per IMWG at 1 year after stopping maintenance therapy	Number of participants that relapse per IMWG	1 year after stopping maintenance therapy
Number of participants that relapse per IMWG at 2 years after stopping maintenance therapy	Number of participants that relapse per IMWG	2 years after stopping maintenance therapy
Progression-free survival (PFS) in multiple myeloma patients	PFS in multiple myeloma patients at 1 year	I year
Progression-free survival (PFS) in multiple myeloma patients	PFS in multiple myeloma patients at 2 years	2 years
Progression-free survival (PFS) in multiple myeloma patients	PFS in multiple myeloma patients at 3 years	3 years
Compare health-related quality of life (HRQoL) between MM patients stopping versus continuing maintenance therapy	Compare health-related quality of life (HRQoL) between MM patients stopping versus continuing maintenance therapy therapy using the European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma questionnaire (EORTC QLQ-MY20) questionnaire	Baseline
Compare health-related quality of life (HRQoL) between MM patients stopping versus continuing maintenance therapy	Compare health-related quality of life (HRQoL) between MM patients stopping versus continuing maintenance therapy using the European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma questionnaire (EORTC QLQ-MY20) questionnaire	3 months
Correlate peripheral blood circulating myeloma cell numbers (CELLSEARCH) with conventional IMWG response	Measuring the disease response	1 year
Correlate peripheral blood circulating myeloma cell numbers (CELLSEARCH) with conventional IMWG response	Measuring the disease response	2 years
Correlate peripheral blood circulating myeloma cell numbers (CELLSEARCH) with conventional IMWG response	Measuring the disease response	3 years
Correlate peripheral blood circulating myeloma cell numbers (CELLSEARCH) with conventional IMWG response	PFS in multiple myeloma patients at 1 year	1 year
Correlate peripheral blood circulating myeloma cell numbers (CELLSEARCH) with conventional IMWG response	PFS in multiple myeloma patients at 2 years	2 years
Correlate peripheral blood circulating myeloma cell numbers (CELLSEARCH) with conventional IMWG response	PFS in multiple myeloma patients at 3 years	3 years

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Investigators: Principal Investigator: Karen Sweiss, PhamD, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2021
• Primary Completion (Anticipated): January 1, 2029
• Study Completion (Anticipated): January 1, 2029

Study Registration Dates

• First Submitted: January 7, 2022
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 14, 2022

Study Record Updates

• Last Update Posted (Actual): October 6, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplastic Processes; Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasm, Residual
• Other Study ID Numbers: 2021-1196

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No