Fixed Duration vs Continuous Anti-CD38 Antibody Therapy Among Transplant Ineligible Older Adults With Newly-Diagnosed Multiple Myeloma

A Phase III Non-Inferiority Randomized Controlled Trial of Fixed Duration Versus Continuous Anti-CD38 Antibody Therapy Among Transplant Ineligible Older Adults With Newly-Diagnosed Multiple Myeloma

Currently, daratumumab or isatuximab are given continuously (non-stop), along side lenalidomide, and dexamethasone as part of multiple myeloma treatment. are given continuously (non-stop). Recent observations suggest that stopping daratumumab or isatuximb after about a year and a half of treatment may work just as well as giving them continuously with lenalidomide and dexamethasone. Sometimes, bortezomib is also given. This study is being done to answer the question: is less daratumumab or isatuximab treatment as good as more?

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide; Drug: Dexamethasone; Drug: Daratumumab; Drug: Isatuximab

Detailed Description

The usual approach for people with myeloma who are not having a stem cell transplant is treatment with daratumumab or isatuximab in combination with 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 or isatuximab 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
• Enrollment (Estimated): 570
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Annette Hay; Phone Number: 613-533-6430; Email: ahay@ctg.queensu.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Cross Cancer Institute
      • Contact: Steven Shih
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Recruiting
      • BCCA - Kelowna
      • Contact: Erma Gardner; Phone Number: 250 712-3900
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Recruiting
      • BCCA - Vancouver
      • Contact: Christopher Venner
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Recruiting
      • CancerCare Manitoba
      • Contact: Rami R. Kotb; Phone Number: 204 787-2108
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Recruiting
      • The Moncton Hospital
      • Contact: Nizar Abdel-Samad; Phone Number: 506 870-2404
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Recruiting
      • Regional Health Authority B, Zone 2
      • Contact: Anthony J. Reiman; Phone Number: 506 648-6884
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Recruiting
      • Dr. H. Bliss Murphy Cancer Centre
      • Contact: Debra Bergstrom; Phone Number: 709 777-7557
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Recruiting
      • Royal Victoria Regional Health Centre
      • Contact: Rouslan Kotchetkov
    • Brampton, Ontario, Canada, L6R 3J7
      • Recruiting
      • William Osler Health System
      • Contact: Shyam Ravisankar
    • Hamilton, Ontario, Canada, L8V 5C2
      • Recruiting
      • Juravinski Cancer Centre at Hamilton Health Sciences
      • Contact: Hira Mian; Phone Number: 905 387-9495
    • Kingston, Ontario, Canada, K7L 2V7
      • Recruiting
      • Kingston Health Sciences Centre
      • Contact: Bethany Monteith
    • Kitchener, Ontario, Canada, N2G 1G3
      • Recruiting
      • Waterloo Regional Health Network (WRHN)
      • Contact: Armela Dicu; Phone Number: 519 749-4370
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • London Health Sciences Centre Research Inc.
      • Contact: Martha Louzada; Phone Number: 519 685-2391
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Recruiting
      • Stronach Regional Health Centre at Southlake
      • Contact: Peter James Anglin; Phone Number: 905 895-4521
    • Oshawa, Ontario, Canada, L1G 2B9
      • Recruiting
      • Lakeridge Health Oshawa
      • Contact: Ariah Joshua Schattner; Phone Number: 905 576-8711
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Ottawa Hospital Research Institute
      • Contact: Arleigh B. Robertson McCurdy; Phone Number: 613 737-7700
    • Sault Ste. Marie, Ontario, Canada, P6B 0A8
      • Recruiting
      • Algoma District Cancer Program
      • Contact: Danny Hill; Phone Number: 4450 705 759-3434
    • St. Catharines, Ontario, Canada, L2S 0A9
      • Recruiting
      • Niagara Health System
      • Contact: Huma Qawi; Phone Number: 43801 905 684-7271
    • Toronto, Ontario, Canada, M5B 1W8
      • Recruiting
      • St. Michael's Hospital
      • Contact: Martina Trinkaus; Phone Number: 416 864-5632
    • Toronto, Ontario, Canada, M6R 1B5
      • Recruiting
      • St. Joseph's Health Centre
      • Contact: Christie Kim
    • Windsor, Ontario, Canada, N8W 2X3
      • Recruiting
      • Windsor Regional Cancer Centre
      • Contact: Sindu Mary Kanjeekal; Phone Number: 58616 519 253-5253
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • The Jewish General Hospital
      • Contact: Rayan Kaedbey; Phone Number: 614 340-8222
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • The Research Institute of the McGill University
      • Contact: Michael Sebag; Phone Number: 514 398-8307
    • Montreal, Quebec, Canada, H1T 2M4
      • Recruiting
      • CIUSSS de l'Est-de-I'lle-de-Montreal
      • Contact: Richard LeBlanc; Phone Number: 3404 514 252-3400
    • Montreal, Quebec, Canada, H3T 1M5
      • Recruiting
      • St. Mary's Hospital
      • Contact: Tanya Skamene; Phone Number: 514 340-8222
    • Québec, Quebec, Canada, G1J 1Z4
      • Recruiting
      • CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)
      • Contact: Julie Cote; Phone Number: 63115 418 525-4444
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Recruiting
      • Allan Blair Cancer Centre
      • Contact: Ibraheem Mohammed Othman; Phone Number: 306 766-2691
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Recruiting
      • Saskatoon Cancer Centre
      • Contact: Julie Stakiw; Phone Number: 306 655-2980

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 monoclonal protein (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
• Completed 18-20 cycles of daratumumab-lenalidomide-dexamethasone or isatuximab-lenalidomide-dexamethasone.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenalidomide & Dexamethasone	Drug: Lenalidomide; Dose determined at enrollment; Drug: Dexamethasone; Dose determined at enrollment
Active Comparator: Daratumumab, Lenalidomide, Dexamethasone & Isatuximab; Standard of Care	Drug: Lenalidomide; Dose determined at enrollment; Drug: Dexamethasone; Dose determined at enrollment; Drug: Daratumumab; Dose determined at enrollment; Drug: Isatuximab; Dose determined at enrollment

What is the study measuring?

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	9.1 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from enrollment to death from any cause	9.1 years
Partial Response or Better as assessed by IMWG Criteria		9.1 years
Incidence of Treatment-Related Grade 3-5 Adverse Events and all infections based on CTCAE 5.0		9.1 years
Time to Next Treatment	Time from enrollment to the start of next-line treatment	9.1 years
Post-protocol Therapy Documentation checklist	Documentation of patients 2nd line treatment after treatment completion of daratumumab, or isatuximab, lenalidomide, and dexamethasone	9.1 years
Quality of Life Utilizing EORTC QLQ-C30		9.1 years
Quality of Life Utilizing FACIT-COST		9.1 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	9.1 years

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Collaborators: Canadian Institutes of Health Research (CIHR); Myeloma Canada
• Investigators: Study Chair: Hira Mian, Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, Ontario Canada

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2024
• Primary Completion (Estimated): January 31, 2032
• Study Completion (Estimated): July 31, 2032

Study Registration Dates

• First Submitted: December 13, 2023
• First Submitted That Met QC Criteria: December 26, 2023
• First Posted (Actual): December 27, 2023

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Polycyclic Compounds; Piperidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Dexamethasone; daratumumab; isatuximab
• Other Study ID Numbers: MY13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No