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

Official title

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

Overview

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?

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.

Interventions

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

Primary outcome measures

• Progression-Free Survival [Time frame: 9.1 years]

Secondary outcome measures (8)

• Overall Survival [Time frame: 9.1 years]
• Partial Response or Better as assessed by IMWG Criteria [Time frame: 9.1 years]
• Incidence of Treatment-Related Grade 3-5 Adverse Events and all infections based on CTCAE 5.0 [Time frame: 9.1 years]
• Time to Next Treatment [Time frame: 9.1 years]
• Post-protocol Therapy Documentation checklist [Time frame: 9.1 years]
• Quality of Life Utilizing EORTC QLQ-C30 [Time frame: 9.1 years]
• Quality of Life Utilizing FACIT-COST [Time frame: 9.1 years]
• Health Economic Analyses Utilizing EQ-5D-5L [Time frame: 9.1 years]

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 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 28 centers

• Cross Cancer Institute — Edmonton
• BCCA - Kelowna — Kelowna
• BCCA - Vancouver — Vancouver
• CancerCare Manitoba — Winnipeg
• The Moncton Hospital — Moncton
• Regional Health Authority B, Zone 2 — Saint John
• Dr. H. Bliss Murphy Cancer Centre — St. John's
• Royal Victoria Regional Health Centre — Barrie
• … and 20 more centers

Identifiers

NCT: NCT06182774 · MY13

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗