Fixed Duration vs Continuous Daratumumab in Transplant Ineligible Older Adults With Newly Diagnosed Multiple Myeloma

Study Overview
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Brief Summary
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Currently, daratumumab, lenalidomide, and dexamethasone are given continuously (non-stop). Some recent observations suggest that stopping daratumumab after about a year and a half of treatment may work just as well as giving it continuously with lenalidomide and dexamethasone. This study is being done to answer the question: is less daratumumab treatment as good as more?

Detailed Description
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The usual approach for people with myeloma who are not having a stem cell transplant is treatment with the combination of daratumumab, lenalidomide, and dexamethasone. These drugs are given continuously until they are no longer effective or cause major side effects. Those that decide to take part in this study, will be randomly placed in one of two groups. If in the usual care group, patients will continue all the myeloma medicines currently being taken. If in the experimental group, patients will stop the daratumumab injection, and continue taking the myeloma tablets currently being taken. Regardless of which group, patients will stay on treatment indefinitely as long they are benefiting from it.

Official Title
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A Phase III Non-Inferiority Randomized Controlled Trial of Fixed Duration Versus Continuous Daratumumab Among Transplant Ineligible Older Adults With Newly Diagnosed Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Daratumumab
* Drug: Lenalidomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with newly diagnosed multiple myeloma that are transplant-ineligible Measurable disease at the time of diagnosis, as defined by at least one of the following criteria: Serum M-protein ≥ 5 g/L; Urine M-protein ≥ 200 mg/24 hours; Involved serum free light chain measurement ≥ 100 mg/L, provided serum FLC ration is abnormal; For IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin ≥ 750 mg/dL Received daratumumab-lenalidomide-dexamethasone for 18-20 cycles Obtained at least a partial response per the standard 2016 IMWG criteria ECOG performance status 0-3 Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life and/or health utility questionnaires in English, French, or a provided validated language. Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Participants must be accessible for treatment and follow-up. In accordance with CCTG policy, protocol treatment is to begin within 2 working days of participant enrollment. Participants of childbearing potential must have agreed to use a highly effective contraceptive method. Exclusion Criteria: Known history of concurrent amyloid light chain amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), and Waldenstrom's macroglobulinemia. Patients receiving concurrent treatment with other anti-cancer therapy that would impact the ability to comply with protocol treatment are ineligible. Note: Participants 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 protocol treatment are eligible for this trial Active, uncontrolled bacterial, fungal, or viral infection within 7 days prior to enrollment. Known human immunodeficiency virus (HIV) with CD4 count < 350 cells/microliter. Note that patients who are HIV positive are eligible, provided: They are under treatment with antiretroviral therapy for at least 4 weeks prior to enrollment, with acceptable pharmacokinetic interactions and minimal overlapping toxicity with protocol therapy AND HIV viral load must be < 400 copies/ml within 16 weeks prior to enrollment AND No history of opportunistic infections within the past year.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide & Dexamethasone<br> | Drug: Lenalidomide<br>* Dose determined at enrollment<br>Drug: Dexamethasone<br>* Dose determined at enrollment<br>|
| Active Comparator: Daratumumab, Lenalidomide & Dexamethasone<br>Standard of Care | Drug: Daratumumab<br>* Dose determined at enrollment<br>Drug: Lenalidomide<br>* Dose determined at enrollment<br>Drug: Dexamethasone<br>* Dose determined at enrollment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival | PFS is defined as the time from date of enrollment to date of first documentation of disease progression | 8.1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time from enrollment to death from any cause | 8.1 years | 
| Partial Response or Better as assessed by IMWG Criteria |  | 8.1 years | 
| Incidence of Treatment-Related Grade 3-5 Adverse Events and all infections based on CTCAE 5.0 |  | 8.1 years | 
| Time to Next Treatment | Time from enrollment to the start of next-line treatment | 8.1 years | 
| Post-protocol Therapy Documentation checklist | Documentation of patients 2nd line treatment after treatment completion of daratumumab, lenalidomide, and dexamethasone | 8.1 years | 
| Quality of Life Utilizing EORTC QLQ-C30 |  | 8.1 years | 
| Quality of Life Utilizing FACIT-COST |  | 8.1 years | 
| Health Economic Analyses Utilizing EQ-5D-5L | Value is calculated by determining the incremental costs and benefits (life years, quality adjusted life years) across the two treatment arms from two perspectives, a health system and a societal perspective | 8.1 years |