Aging, Co-morbidity, Multiple Myeloma, Refractory, Relapse
Conditions
Keywords
Pomalidomide, Isatuximab, Dexamethasone, low dose
Brief summary
This research study aims to evaluate the safety and effectiveness of the combination of isatuximab, pomalidomide, and dexamethasone (Isa-Pd) for the treatment of relapsed or refractory multiple myeloma (RRMM), which refers to multiple myeloma that has returned or has not responded to prior treatment. The study will specifically investigate the impact of administering lower-than-standard doses of pomalidomide and dexamethasone. Using lower doses of pomalidomide and dexamethasone in this setting has not been approved by the Food and Drug Administration (FDA).
Detailed description
This study aims to address the challenges faced in selecting appropriate therapy for elderly or highly toxicity-vulnerable patients who are poor candidates for standard (full-dose) chemotherapy regimens. Traditional clinical trials often exclude these patients, limiting the generalizability of available data. This single-arm multicenter phase II study will enroll 49 older and/or toxicity-vulnerable patients with RRMM. The study will evaluate the safety and effectiveness of isatuximab when used in combination with pomalidomide and dexamethasone at lower than standard doses. The primary objective is to estimate the overall response rate (ORR), while secondary objectives include the estimation of additional measures of response, as well as measures of toxicity and tolerability. All participants in 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). Biomarkers of aging and frailty will also be studied. Duration of therapy: The duration of study participation will depend on the response to the treatment. In the absence of treatment delays due to adverse events, treatment with Isa-Pd will generally continue until disease progression, unacceptable side effects, other illness or condition that prevents further study treatment, or a subject's decision to withdraw from the study. On average, subjects will most likely be treated for approximately 10 months on this study. Duration of Follow-Up: All participants, including those withdrawn for adverse events (AEs) will be followed after removal from study treatment until death or full subject withdrawal from the study for other reasons. Participants removed from the study treatment for unacceptable AEs will be followed for resolution or stabilization of the AEs.
Interventions
DRUGIsatuximab
Pharmaceutical form: Solution for infusion. Route of administration: Intravenous 10 mg/kg will be administered intravenously once weekly during cycle 1 and every other week during each subsequent cycle.
DRUGPomalidomide
Pharmaceutical form: Pill for oral use. Route of administration: 3 mg Pomalidomide 3 mg pill will be taken by mouth once daily on days 1-21 of each 28-day cycle.
DRUGDexamethasone
Pharmaceutical form: Tablet for oral use Route of administration: Pill for oral use. Dexamethasone 20 mg tablet will be taken by mouth once per week.
Sponsors
UNC Lineberger Comprehensive Cancer Center
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information (PHI). Consent must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. 2. Age ≥ 18 years at the time of consent. 3. Documented symptomatic multiple myeloma that has previously responded to therapy (partial response or better) and is relapsed or relapsed and refractory to the last line of therapy. 4. Patients must also be refractory to at least one prior line of therapy that includes an IMiD and/or a PI, and should have received at least 2 cycles of that regimen to be evaluable for refractoriness . 5. If previously treated with an anti-CD38 containing regimen, the subject must have achieved at least a PR to that line of therapy and must not have received an anti- CD38 mAb for at least 6 months prior to enrollment. 6. Willing and able to adhere to the study visit schedule and other protocol requirements based on the judgement of the investigator. 7. Predicted high risk for severe toxicity from intensive regimens for RRMM, such as standard (full-dose) DPD, DVD, KPD, KRD, Ixa-PD, or Elo-PD as each regimen was published (such regimens often use, for example, twice-weekly bortezomib at 1.3 mg/m2, lenalidomide at 25 mg, or pomalidomide 4 mg). High-risk is defined as one of the following: A. Score ≥ 2 (indicating "frail") on the International Myeloma Working Group instrument (IMWG; Palumbo et al. \[Blood 2015\]) B.KPS ≤ 70 C. Not meeting criteria A or B above but felt by treating clinician to not be a candidate for a standard full-dose regimen on account of one of the following: i) History of clinically significant non-hematologic grade ≥3 (NCI CTCAE, version 5.0) toxicity attributed to prior anticancer therapy ii) History of requiring dose-reduction of at least two separate anticancer drugs during prior therapy for multiple myeloma.
Exclusion criteria
All subjects meeting any of the listed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 12 weeks | Overall response rate (ORR) is defined as the percentage of participants achieving a partial response or better (≥PR) per IMWG criteria. The number and percentage of participants achieving at least a partial response were reported. Complete response (CR) requires negative serum and urine immunofixation, disappearance of plasmacytomas, and \<5% bone marrow plasma cells; stringent complete response (sCR) requires CR plus a normal free light chain ratio and no clonal plasma cells in bone marrow. Very good partial response (VGPR) is defined as M-protein detectable by immunofixation but not electrophoresis, or a ≥90% reduction in serum M-protein with urine M-protein \<100 mg/24h. Partial response (PR) is defined as a ≥50% reduction in serum M-protein and a ≥90% reduction in 24-hour urine M-protein (or to \<200 mg/24h), with a ≥50% reduction in plasmacytomas if present at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Related Adverse Events Rate | Up to 12 weeks | All treatment-related adverse events as defined by changes from baseline utilizing 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. |
| Treatment Failure-free Survival (TFFS) | Up to 3 years | TFFS is defined as the time start from the first day of study therapy until discontinuation for any reason, including disease progression, toxicity, or death. Progressive disease: Serum M-protein: absolute increase must be ≥ 0.5 g/dL, ≥ 1 g/dL if the lowest M component was ≥ 5 g/dL; absolute Urine M-protein increase≥ 200 mg/24 h). In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels must be \> 10 mg/dL; without measurable involved FLC levels, bone marrow plasma cell percentage irrespective of baseline status Appearance of a new lesion(s), ≥ 50% increase from nadir \> 1 lesion, or ≥ 50% increase in the longest diameter of a previous lesion \>1 cm in short axis;≥ 50% increase e in circulating plasma cells (minimum of 200 cells per μL) if this is the only measure of disease. |
| Maximum Depth of Response | Up to 12 weeks | Maximum depth of response includes the summation of minimal response (MR), partial response (PR), very good partial response (VGPR), complete response (CR), and stringent complete response (sCR) based on IMWG criteria. Minimal response(MR): ≥ 25% but ≤ 49% reduction of serum M-protein and reduction in 24-h urine M-protein by 50-89%, if present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required. PR, VGPR, CR, and sCR were defined above. |
| Clinical Benefit Rate (CBR) | Up to 12 weeks | CBR is defined as a partial response or better (≥PR) + minimal response (MR) rate based on International Myeloma Working Group (IMWG) criteria. |
| Bone Marrow Minimal Residual Disease (MRD) Negativity | Up to 12 weeks | Bone marrow minimal residual disease (MRD) negativity will be defined as the ratio of subjects who achieved MRD to all subjects. MRD negativity will be assessed by next-generation sequencing with a minimum sensitivity of 1x10-5. |
| Time to First Response | Up to 12 weeks | Time to first response is defined as the time from the first study treatment to the achievement of PR or better as defined by IMWG criteria. |
| Time to Best Response | Up to 12 weeks | Time to best response is defined as the time from the first study treatment to the achievement of best response (PR, VGPR, CR, or sCR) based on IMWG criteria. |
| Duration of Response | Up to 3 years | Duration of response is defined as the time from the achievement of PR or better until progressive disease (PD) based on IMWG criteria. Subjects will be censored if they die of anything other than myeloma. |
| Progression-free Survival (PFS) | Up to 3 years | PFS is defined as the time from the first study treatment until confirmed PD based on IMWG criteria or death from any cause, whichever comes first. |
| Median Time to Next Treatment (TTNT) | Up to 3 years | Median time to next treatment (TTNT) is defined as the time from the start of the study treatment to the next type of Multiple Myeloma treatment or death from any cause, whichever occurs first. |
| Overall Survival | Up to 3 years | Overall survival is defined as the time from the first study treatment to death from any cause. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREben I Lichtman, MD
UNC Lineberger Comprehensive Cancer Center
Participant flow
Pre-assignment details
Six participants were enrolled at a single U.S. center between December 5, 2023, and March 20, 2025.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 72 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
None listed