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Free from Maintenance Drug Therapy in Multiple Myeloma (The FREEDMM Trial) for Minimal Residual Disease (MRD

Phase 1
Recruiting
Conditions
Multiple Myeloma
Interventions
Other: Discontinue maintenance therapy SOC
Registration Number
NCT05192122
Lead Sponsor
University of Illinois at Chicago
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
50
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Bone marrow MRD-negative VGPR or CRDiscontinue maintenance therapy SOCDiscontinue maintenance therapy after at least three years
Bone marrow MRD-positive VGPR or CRDiscontinue maintenance therapy SOCContinue maintenance therapy as per SOC
Primary Outcome Measures
NameTimeMethod
Number of participants that have a sustained MRD-negative VGPR or CR measured by a bone marrow biopsy12 months after stopping maintenance therapy

Number of participants that have a sustained MRD-negative VGPR or CR measured by a bone marrow biopsy (MRD defined as 10-6)

Secondary Outcome Measures
NameTimeMethod
Number of participants that relapse per IMWG at 1 year after stopping maintenance therapy1 year after stopping maintenance therapy

Number of participants that relapse per IMWG

Compare health-related quality of life (HRQoL) between MM patients stopping versus continuing maintenance therapy3 months

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

Number of participants that relapse per IMWG at 2 years after stopping maintenance therapy2 years after stopping maintenance therapy

Number of participants that relapse per IMWG

Progression-free survival (PFS) in multiple myeloma patients3 years

PFS in multiple myeloma patients at 3 years

Number of participants that have a sustained MRD-negative VGPR or CR measured by a bone marrow biopsy2 years after stopping maintenance therapy

Number of participants that have a sustained MRD-negative VGPR or CR measured by a bone marrow biopsy (MRD defined as 10-6)

Correlate peripheral blood circulating myeloma cell numbers (CELLSEARCH) with conventional IMWG response3 years

PFS in multiple myeloma patients at 3 years

Trial Locations

Locations (1)

University of Illinois Cancer Center

🇺🇸

Chicago, Illinois, United States

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