Isa-Rd for Frail and/or Much Older Patients With Newly Diagnosed Multiple Myeloma
- Conditions
- Multiple MyelomaCancer
- Interventions
- Registration Number
- NCT05145400
- Lead Sponsor
- UNC Lineberger Comprehensive Cancer Center
- Brief Summary
This research study is investigating the safety and effectiveness of using combination of isatuximab, lenalidomide and dexamethasone for the treatment of newly diagnosed multiple myeloma (MM). The study team will use lower doses than is currently standard for these drugs. Lower doses will be used to avoid or possibly reduce any unwanted side effects commonly associated with these drugs. Using lower doses of the combination isatuximab, lenalidomide and dexamethasone, has not been approved by the Food and Drug Administration (FDA) for the treatment of newly diagnosed MM.
- Detailed Description
This study aims to determine the optimal treatment regimen for older and/or otherwise toxicity-vulnerable patients with newly diagnosed multiple myeloma (NDMM) who cannot receive approved standard therapy. As a result, this Phase II trial of isatuximab, lenalidomide, and dexamethasone (Isa-Rd) selectively enroll much older and/or otherwise highly toxicity-vulnerable participants. Furthermore, the safety and effectiveness of isatuximab when used in combination with lenalidomide and dexamethasone at lower doses will be evaluated. It is expected that using this combination at lower doses, may help patients achieve a better response while causing fewer or less severe side effects.
All participants on the trial will also be evaluated by Cancer and Aging Research Group Geriatric Assessments (CARG-GA) and patient-reported outcome (PRO) measures of quality of life (QOL). "Geriatric assessment" will be referred to as "global assessment" for study purposes, to reflect the fact that younger participants will likely participate in the study. Optional correlative blood samples will be collected to study biomarkers of aging and frailty with a focus on both the relation to isatuximab specifically, as well as treatment response and risk for intolerability.
Duration of Therapy:
The length of study participation will depend on the response to the treatment, and it may last approximately 2 years. Participants will receive isatuximab for two years, and then isatuximab will be discontinued. Dexamethasone administration will occur weekly for the first eight cycles. Lenalidomide will be continued as maintenance until disease progression or unacceptable toxicity.
In the absence of treatment delays due to adverse events, treatment should continue until:
* Disease progression
* Inter-current illness that prevents further administration of treatment
* Treatment delay of more than 12 weeks.
* Unacceptable adverse event(s)
* Pregnancy
* Subject decides to withdraw from study treatment, or
* General or specific changes in the subject's condition render the subject unacceptable for further treatment in the judgment of the investigator.
* Subject is lost to follow up
Duration of Follow Up:
All participants (including those withdrawn for AE (Adverse Event) will be followed after removal from study treatment until death or full subject withdrawal from the study for other reasons. Participants removed from study treatment for unacceptable AEs will be followed for resolution or stabilization of the adverse event(s).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Single Arm Isatuximab All subjects will receive the same treatment on the study, consisting of isatuximab, lenalidomide, and dexamethasone with 28 days cycles. Single Arm Lenalidomide All subjects will receive the same treatment on the study, consisting of isatuximab, lenalidomide, and dexamethasone with 28 days cycles. Single Arm Dexamethasone All subjects will receive the same treatment on the study, consisting of isatuximab, lenalidomide, and dexamethasone with 28 days cycles.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) From Day 1 of study treatment up to 60 months ORR, percentage of patients achieving a partial response or better per Revised Uniform Response Criteria by the International Myeloma Working Group (IMWG) criteria. Complete response (CR): Negative immunofixation of serum and urine, disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas
- Secondary Outcome Measures
Name Time Method Rate of achievement of bone marrow minimal residual disease (MRD) negativity From Day 1 of study treatment up to 60 months MRD status is determined by next-generation sequencing with a minimum sensitivity of 1 × 10-5. MRD refers to myeloma cells that are present in the bone marrow after a clinical response has been measured while signs and symptoms of MM are reduced or disappeared.
Clinical Benefit Rate (minimal response (MR) + ORR) From Day 1 of study treatment up to 60 months The clinical benefit rate is the percentage of participants achieving overall response or minimal response. Description of overall response as defined as the percentage of subjects achieving a partial response or better (≥ PR) to study therapy at any time. Minimal response (MR) is ≥ 25% but ≤ 49% reduction of serum M-protein and reduction in 24-h urine M-protein by 50-89%. In addition to the above listed criteria, if present at baseline, a ≥ 50% reduction in the size (SPD) of soft tissue plasmacytomas is also required.
Treatment failure-free survival (TFFS) Time From Day 1 of study treatment up to 60 months Treatment failure-free survival (TFFS): The length of time from therapy start until therapy discontinuation for any reason, including disease progression, toxicity, or death.
Maximum Depth of Response From Day 1 of study treatment up to 60 months Maximum depth of response (from PR to CR, including sCR) at any time will be determined based on IMWG criteria. Descriptions of partial, complete, or stringent-complete type treatment responses are summarized in the primary outcome section.
Progression-Free Survival (PFS) From Day 1 of study treatment up to 60 months PFS is the length of time from start of study treatment until day of confirmed progression or death. The (IMWG) defines progression as any one or more: Increase of 25% from lowest response value in Serum M-protein (absolute increase (AI) ≥ 0.5 g/dL); Serum M-protein increase ≥ 1 g/dL, if lowest M component was ≥ 5 g/dL; or Urine M-protein Difference of involved \& uninvolved FLC (free light chain) levels (AI \> 10 mg/dL) Bone marrow plasma cell percentage irrespective of baseline status (AI ≥ 10%) New lesion(s), ≥ 50% increase from nadir, or ≥ 50% increase in longest diameter of previous lesion \>1 cm in short axis; ≥ 50% increase in circulating plasma cells if only measure of disease New or definite increase in size of existing soft tissue plasmacytomas or bone lesions; Decrease in hemoglobin of ≥ 2 g/dL not related to therapy; Rise in serum creatinine by ≥2 mg/dL; Hyperviscosity related to serum paraprotein
Time to Response From Day 1 of study treatment up to 60 months Time to response is the length of time from start of study treatment until documentation of confirmed partial response (PR) or better based on IMWG criteria. Response description is given in the primary outcome section.
Duration of Response From Day 1 of study treatment up to 60 months Duration of response is the length of time from achievement of PR or better until myeloma progression per IMWG criteria. PR description is given in the primary outcome section.
Time to Next Treatment From Day 1 of study treatment up to 60 months Time to next treatment is the length of time time from start of study treatment to next MM treatment or death from any cause.
Overall Survival From Day 1 of study treatment up to 60 months Overall Survival is the length of time from start of study treatment to death from any cause.
Toxicity Rate From Day 1 of study treatment up to 60 months Toxicity rate is percentage of participants who experience treatment related Adverse Events (AE) as evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0. NCI-CTCAE is a descriptive terminology utilized for AE reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Trial Locations
- Locations (5)
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Duke Comprehensive Cancer Center
🇺🇸Durham, North Carolina, United States
Novant Health New Hanover Regional Medical Center
🇺🇸Wilmington, North Carolina, United States
The Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States