Lenalidomide Discontinuation Study

Sponsor

University College Cork (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05866757

Collaborator

Cancer Research@UCC (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

An interventional, non-randomised study to assess the risk of progression after discontinuation of maintenance therapy in sustained MRD negative complete remission by flow cytometry MM patients without high-risk features who have completed at least two years of maintenance therapy with lenalidomide or who have discontinued lenalidomide maintenance due to side effects. The primary endpoint is to assess the rates of sustained MRD negativity by NGF in the bone marrow at 12 months after discontinuation of maintenance therapy.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma Cancer Hematologic Cancer	Other: Discontinuation of maintenance treatment	N/A

Detailed Description

Up to 70 patients over 18 years of age who have a diagnosis of Multiple Myeloma and have completed at least 2 years of lenalidomide maintenance therapy. Participants would be divided in two groups: Group 1. Patients with detectable disease, failed to achieve Complete Remission (CR) or Very Good Partial Remission (VGPR) continuing on maintenance therapy. Group 2. Patients who meet International Myeloma working Group (IMWG) criteria for very good partial response (VGPR) or complete response (CR). Patients who have achieved sustained MRD negative remission by next generation flow cytometry (NGF),defined by IMWG as MRD-negative at two time points that are at least 1 year apart, To the participants in this group will be offered to discontinue maintenance therapy, and it will be further divided in the following subgroups: Subgroup A) Patients who are willing to continue maintenance therapy. Subgroup B) Patients who are willing to discontinue maintenance therapy and continue monitoring. This subgroup will also include patients who have discontinued maintenance therapy earlier than 2 years due to side effects but also achieved sustained MRD negative CR might be also included.

The number of the study participants will be limited by the number of patients treated in CUH who are meeting inclusion criteria.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients will be divided in the following groups: Group 1: Patients with biochemically detectable disease who have failed to achieve Complete remission (CR) or Very good Partial Remission (VGPR) by IMWG criteria and/or MRD-positive and/or high risk features. They will continue maintenance therapy until disease progression with monitoring every 3 months as per standard of care (SOC), or more often if required. Group 2: Patients in biochemical remission, who meet IMWG criteria for very good partial response (VGPR) or complete response (CR and and sustained MRD (defined as MRD-negative at two time points that are at least 1 year apart) without high risk features This group will be divided in the following subgroups: Subgroup A: Patients who prefer to continue on maintenance therapy. Maintenance will continue until disease progression. Subgroup B: Patients who prefer to discontinue maintenance therapy.Patients will be divided in the following groups:Group 1: Patients with biochemically detectable disease who have failed to achieve Complete remission (CR) or Very good Partial Remission (VGPR) by IMWG criteria and/or MRD-positive and/or high risk features. They will continue maintenance therapy until disease progression with monitoring every 3 months as per standard of care (SOC), or more often if required.Group 2: Patients in biochemical remission, who meet IMWG criteria for very good partial response (VGPR) or complete response (CR and and sustained MRD (defined as MRD-negative at two time points that are at least 1 year apart) without high risk features This group will be divided in the following subgroups:Subgroup A: Patients who prefer to continue on maintenance therapy. Maintenance will continue until disease progression. Subgroup B: Patients who prefer to discontinue maintenance therapy.

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Discontinuation of Lenalidomide Maintenance for the Patients Diagnosed With Multiple Myeloma in Sustainable Minimal Residual Disease (MRD) Negative Remission Without High Risk Features

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

May 1, 2025

Anticipated Study Completion Date :

May 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Group 1 Continuing Maintenance Therapy- Patients with biochemically detectable disease who have failed to achieve Complete remission (CR) or Very good Partial Remission (VGPR) by IMWG criteria and/or MRD-positive and/or high risk features. They will continue maintenance therapy until disease progression with monitoring every 3 months as per standard of care (SOC), or more often if required. In case of disease progression these patients will be switched to a different treatment and withdraw from the study. QOL will be assessed.
No Intervention: Group 2 Subgroup A Continuing Maintenance Therapy- Patients in biochemical remission, who meet IMWG criteria for very good partial response (VGPR) or complete response (CR and and sustained MRD (defined as MRD-negative at two time points that are at least 1 year apart) without high risk features. High-risk cytogenetics abnormalities defined as per IMWG criteria (del(17p) and/or t(4;14) and/or t(14;16)) , or any other features suggestive of high risk disease: extramedullary disease, poor response to first line therapy, plasma cell leukaemia, organomegaly secondary to infiltration by multiple myeloma. Maintenance will continue until disease progression, monitored every 3 months as per SOC or more often if required. In case of disease progression these patients will be switched to a different treatment and withdraw from the study. QOL will be assessed.
Other: Group 2 Subgroup B Patients who prefer to discontinue maintenance therapy. Patients who have discontinued maintenance therapy earlier than 2 years due to side effects but also achieved sustained MRD negative CR might be also included in this subgroup. This subgroup will be monitored and per SOC with blood tests, and BM MRD by NGF. In case of detectable disease in any of the samples (blood or BM) they will be offered to restart on maintenance therapy. Changing to a different type of treatment could be also offered to these patients, after discussion with treating physician. In case of being switched to a different treatment patient will withdraw from the study. QOL will be assessed	Other: Discontinuation of maintenance treatment The discontinuation of maintenance treatment in multiple myeloma. Classed as interventional due to treatment being taken away.

Arm

Intervention/Treatment

No Intervention: Group 1

Continuing Maintenance Therapy- Patients with biochemically detectable disease who have failed to achieve Complete remission (CR) or Very good Partial Remission (VGPR) by IMWG criteria and/or MRD-positive and/or high risk features. They will continue maintenance therapy until disease progression with monitoring every 3 months as per standard of care (SOC), or more often if required. In case of disease progression these patients will be switched to a different treatment and withdraw from the study. QOL will be assessed.

No Intervention: Group 2 Subgroup A

Continuing Maintenance Therapy- Patients in biochemical remission, who meet IMWG criteria for very good partial response (VGPR) or complete response (CR and and sustained MRD (defined as MRD-negative at two time points that are at least 1 year apart) without high risk features. High-risk cytogenetics abnormalities defined as per IMWG criteria (del(17p) and/or t(4;14) and/or t(14;16)) , or any other features suggestive of high risk disease: extramedullary disease, poor response to first line therapy, plasma cell leukaemia, organomegaly secondary to infiltration by multiple myeloma. Maintenance will continue until disease progression, monitored every 3 months as per SOC or more often if required. In case of disease progression these patients will be switched to a different treatment and withdraw from the study. QOL will be assessed.

Other: Group 2 Subgroup B

Patients who prefer to discontinue maintenance therapy. Patients who have discontinued maintenance therapy earlier than 2 years due to side effects but also achieved sustained MRD negative CR might be also included in this subgroup. This subgroup will be monitored and per SOC with blood tests, and BM MRD by NGF. In case of detectable disease in any of the samples (blood or BM) they will be offered to restart on maintenance therapy. Changing to a different type of treatment could be also offered to these patients, after discussion with treating physician. In case of being switched to a different treatment patient will withdraw from the study. QOL will be assessed

Other: Discontinuation of maintenance treatment

The discontinuation of maintenance treatment in multiple myeloma. Classed as interventional due to treatment being taken away.

Outcome Measures

Primary Outcome Measures

Number of participants that remain in sustained MRD negative remission by NGF in the bone marrow at 12 months after discontinuation of maintenance therapy. [12 months]

Secondary Outcome Measures

Number of participants that remain in sustained MRD negative remission by NGF in the bone marrow at 24 months after discontinuation of maintenance therapy. [24 months]
Progression-free survival in multiple myeloma patients at 1 year in both groups of patients (on maintenance therapy and those who have discontinued) [1 year]
Progression-free survival in multiple myeloma patients at 2 years in both groups of patients (on maintenance therapy and those who have discontinued) [2 years]
Compare health-related quality of life between MM patients discontinuing versus continuing maintenance therapy using a QOL questionnaire [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18 years of age or over
Patient with diagnosis of multiple myeloma as per IMWC in first line of treatment.
Received at least 2 years of maintenance therapy, defined as any anti-myeloma therapy to prevent disease recurrence and prolong time in remission (i.e., lenalidomide)
Patients who have discontinued maintenance therapy earlier than 2 years due to side effects but also achieved sustained MRD negative CR might be also included
Patients 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 who have received more than one line of therapy or patients who have not completer two years of maintenance therapy, unless maintenance was discontinued voluntarily and the patient has achieved sustainable MRD negative remission.
Patients with plasma cell disorders other than MM: lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia, AL amyloidosis, POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes), etc…
Prior organ transplant or condition requiring immunosuppressive therapy.
Prior allogenic haematopoietic cell transplant
Treatment with any investigational therapy that does not include maintenance as a part of the treatment strategy.
Unable to sign an informed consent form.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cork University Hospital	Cork		Ireland

Sponsors and Collaborators

University College Cork
Cancer Research@UCC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University College Cork

ClinicalTrials.gov Identifier:

NCT05866757

Other Study ID Numbers:

22107

First Posted:

May 19, 2023

Last Update Posted:

May 19, 2023

Last Verified:

May 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by University College Cork

Multiple Myeloma

Cancer

Additional relevant MeSH terms:

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Study Results

No Results Posted as of May 19, 2023