Clinical trial NCT06182774: Fixed Duration vs Continuous Daratumumab in Transplant Ineligible Older Adults With Newly Diagnosed Multiple Myeloma
Official title: A Phase III Non-Inferiority Randomized Controlled Trial of Fixed Duration Versus Continuous Daratumumab Among Transplant Ineligible Older Adults With Newly Diagnosed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Myeloma Canada
First posted: 2023-12-27
Enrollment: 559
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-Free Survival
timeFrame: 8.1 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 8.1 years
measure: Partial Response or Better as assessed by IMWG Criteria
timeFrame: 8.1 years
measure: Incidence of Treatment-Related Grade 3-5 Adverse Events and all infections based on CTCAE 5.0
timeFrame: 8.1 years
measure: Time to Next Treatment
timeFrame: 8.1 years
measure: Post-protocol Therapy Documentation checklist
timeFrame: 8.1 years
measure: Quality of Life Utilizing EORTC QLQ-C30
timeFrame: 8.1 years
measure: Quality of Life Utilizing FACIT-COST
timeFrame: 8.1 years
measure: Health Economic Analyses Utilizing EQ-5D-5L
timeFrame: 8.1 years
Other outcomes:
Locations:
city: Kelowna
country: Canada
facility: BCCA - Kelowna
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Moncton
country: Canada
facility: The Moncton Hospital
state: New Brunswick
city: Saint John
country: Canada
facility: Regional Health Authority B, Zone 2
state: New Brunswick
city: St. John's
country: Canada
facility: Dr. H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Brampton
country: Canada
facility: William Osler Health System
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Kitchener
country: Canada
facility: Waterloo Regional Health Network (WRHN)
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre Research Inc.
state: Ontario
city: Newmarket
country: Canada
facility: Stronach Regional Health Centre at Southlake
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Sault Ste. Marie
country: Canada
facility: Algoma District Cancer Program
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Joseph's Health Centre
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de l'Est-de-I'lle-de-Montreal
state: Quebec
city: Montreal
country: Canada
facility: The Jewish General Hospital
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Ontario Canada
name: Hira Mian
role: STUDY_CHAIR
References: