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

• ClinicalTrials.gov Identifier: NCT06182774
• Recruitment Status: Recruiting
• First Posted: December 27, 2023
• Last Update Posted: April 12, 2024
• Sponsor: Canadian Cancer Trials Group
• Collaborators: Canadian Institutes of Health Research (CIHR); Myeloma Canada
• Information provided by (Responsible Party): Canadian Cancer Trials Group

Tracking Information

• First Submitted Date: December 13, 2023
• First Posted Date: December 27, 2023
• Last Update Posted Date: April 12, 2024
• Actual Study Start Date: April 10, 2024
• Estimated Primary Completion Date: January 31, 2032 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 26, 2023)

Progression-Free Survival [ Time Frame: 8.1 years ]

PFS is defined as the time from date of enrollment to date of first documentation of disease progression

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 26, 2023)

• Overall Survival [ Time Frame: 8.1 years ]
  Time from enrollment to death from any cause
• Partial Response or Better as assessed by IMWG Criteria [ Time Frame: 8.1 years ]
• Incidence of Treatment-Related Grade 3-5 Adverse Events and all infections based on CTCAE 5.0 [ Time Frame: 8.1 years ]
• Time to Next Treatment [ Time Frame: 8.1 years ]
  Time from enrollment to the start of next-line treatment
• Post-protocol Therapy Documentation checklist [ Time Frame: 8.1 years ]
  Documentation of patients 2nd line treatment after treatment completion of daratumumab, lenalidomide, and dexamethasone
• Quality of Life Utilizing EORTC QLQ-C30 [ Time Frame: 8.1 years ]
• Quality of Life Utilizing FACIT-COST [ Time Frame: 8.1 years ]
• Health Economic Analyses Utilizing EQ-5D-5L [ Time Frame: 8.1 years ]
  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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: Daratumumab
  Dose determined at enrollment
• Drug: Lenalidomide
  Dose determined at enrollment
• Drug: Dexamethasone
  Dose determined at enrollment

Study Arms

• Experimental: Lenalidomide & Dexamethasone
  Interventions:

  • Drug: Lenalidomide
  • Drug: Dexamethasone
• Active Comparator: Daratumumab, Lenalidomide & Dexamethasone
  Standard of Care
  Interventions:

  • Drug: Daratumumab
  • Drug: Lenalidomide
  • Drug: Dexamethasone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 26, 2023): 559
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 31, 2032
• Estimated Primary Completion Date: January 31, 2032 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Annette Hay; 613-533-6430; ahay@ctg.queensu.ca

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT06182774
• Other Study ID Numbers: MY13
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Individual patient data may be shared once the final analysis is complete following the Canadian Cancer Trials Group Data Sharing Policy available at https://ctg.queensu.ca/
• URL: http://ctg.queensu.ca/

• Current Responsible Party: Canadian Cancer Trials Group
• Original Responsible Party: Same as current
• Current Study Sponsor: Canadian Cancer Trials Group
• Original Study Sponsor: Same as current

Collaborators

• Canadian Institutes of Health Research (CIHR)
• Myeloma Canada

Investigators

• Study Chair: Hira Mian; Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Ontario Canada

• PRS Account: Canadian Cancer Trials Group
• Verification Date: April 2024