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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Other: Discontinue maintenance therapy SOC


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Discontinue maintenance therapy after 3 years for Bone marrow MRD-negative VGPR or CR (on 2 separate occasions 12 months apart) Continue maintenance therapy per standard of care (SOC) for Bone marrow MRD-positive VGPR or CR
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |