Myeloma Multiple
Conditions
Brief summary
This is a single-arm, non-inferiority study in which patients who have achieved a very good partial response (VGPR) or better, according to International Myeloma Working Group (IMWG) response criteria, following 6 to 9 months of treatment with teclistamab, a B-cell maturation antigen (BCMA)-directed T-cell engager (anti-BCMAxCD3 bispecific antibody), will be offered monitored drug discontinuation. Teclistamab is typically dosed on a regular schedule (every 1-4 weeks) indefinitely until disease progression (continuous therapy). Here, a limited-duration regimen will be studied in which patients achieving ≥VGPR after 6-9 months of standard teclistamab dosing will discontinue therapy and resume if laboratory or clinical parameters suggest early disease progression (limited-duration therapy). Patients will enter the clinical trial protocol after completing 6-9 months of standard teclistamab monotherapy and achieving ≥VGPR. The study's hypothesis is that the failure probability six months after stopping teclistamab in this patient population will be non-inferior compared to that of historical controls treated with continuous therapy. Reducing drug exposure may be beneficial by reducing risk of infection and reducing anti-BCMA selective pressure toward generation of BCMA-negative relapses. Analysis of minimal residual disease (MRD), tumor features, and bone marrow microenvironment parameters, which will be pursued as exploratory correlative analyses in this study, may identify factors that predict durable response to limited-duration therapy and thereby enable more precise selection of patients likely to benefit from this approach. A subset of patients will be enrolled on a biomarker study for analysis of these exploratory endpoints.
Interventions
OTHEROff Drug Surveillance
After stopping teclistamab, participants will be monitored monthly by standard serum paraprotein studies for disease progression. Participants will resume teclistamab at time of disease progression. After Teclistamab therapy re-initiation on-study, monthly response assessments and data for other study endpoints will be obtained. All participants will undergo peripheral blood collection for correlative research studies at baseline and every two months on-study. Participants who enroll on the biomarker sub-study will undergo bone marrow examination and peripheral blood collection for correlative studies at study entry, at time of disease progression and at six months from enrollment.
Sponsors
Abramson Cancer Center at Penn Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Teclistamab is the study drug. The intervention is the cessation of the drug.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be age ≥18 and able to give written, informed consent. * Participants must have initiated teclistamab (first full dose) 6-9 months prior to enrollment and received an average teclistamab dose of at least 1.5 mg/kg/month since the date of the first 1.5 mg/kg dose. * Participants must have received a teclistamab dose within 4 weeks prior to enrollment. * Participants must have had measurable disease according to IMWG criteria within 1 month prior to teclistamab initiation or first full teclistamab dose * Participants must have achieved a confirmed VGPR or better to teclistamab therapy at any assessment prior to enrollment and have ongoing response (i.e., no disease progression) at time of enrollment per IMWG consensus criteria (Appendix 14.3). * Prior to initiating teclistamab, participants must have received therapy with a proteasome inhibitor, thalidomide analog (lenalidomide or pomalidomide), and an anti-CD38 antibody and meet one of the following criteria: 1. ≥3 prior lines of therapy (with lines-of-therapy delineated according to IWMG guidelines) 2. Refractory to both a proteasome inhibitor and a thalidomide analog. * Participants must have had an ECOG performance status of 0-2 at time of teclistamab initiation; in addition, ECOG performance status must be 0-1 at time of enrollment. * Participants must not have known diagnoses of systemic amyloidosis or POEMS syndrome.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Failure free at six months following teclistamab discontinuation | Six months after teclistamab discontinuation | Failure-free survival is defined as the rate of evaluable individuals who have not experienced any of the following predefined failure events within 6 months of discontinuing teclistamab. Failure is defined as earliest occurrence of any of the following: Participants who progress by IMWG criteria after discontinuing teclistamab, failure to achieve at least minimal response within 90 days after reinitiating teclistamab or failure to resume teclistamab within 90 days of IMWG-defined disease progression. Participants who reinitiate teclistamab due to rise in disease markers before IMWG criteria for disease progression are met, disease progression by IMWG criteria after reinitiation of teclistamab. Initiation of non-teclistamab systemic multiple myeloma therapy. Failure date will be defined as the date of initiating subsequent therapy. Death due to complications of multiple myeloma, teclistamab therapy, or infection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-to-treatment failure | Two years after teclistamab discontinuation | Time-to-treatment failure as defined in the primary endpoint |
| Re-initiation rate | Six months after teclistamab discontinuation | Proportion of subjects who re-initiate teclistamab within six months following discontinuation |
| Rate of response to teclistamab re-initiation | Two years after teclistamab discontinuation | Among subjects with IMWG-defined measurable disease at time of teclistamab re-initiation, overall response rate (PR or better) and clinical benefit rate (minimal response or better) to teclistamab upon re-initiating therapy. |
| Time to progression and progression-free survival | Two years after teclistamab discontinuation. | Time-to-progression and progression-free survival by IMWG criteria from time of teclistamab discontinuation, using the best response to initial teclistamab course as the baseline for scoring disease progression. |
| Rate and type of clinical complications of progressive disease | Six months after teclistamab discontinuation | Frequency of the type and rate of clinical complications of progressive disease (e.g., new osteolytic lesions) from time of teclistamab discontinuation through 6 months post-discontinuation. |
| Quality of life | Two years after teclistamab discontinuation | QOL is measured using the MM-FACT instrument. Health-related quality of life (HRQoL) as measured by Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) questionnaire score at enrollment and monthly post-enrollment assessments. The higher the score, the better the quality of life. Two scores will be derived - FACT-MM Trial Outcome Index (TOI) (range: 0-112) and FACT-MM total score (range: 0-164). |
| Mean percent change in peripheral blood studies | Two years after teclistamab discontinuation | Mean percent change in peripheral blood cell counts, immunoglobulin levels, and T cell counts (total and CD4/CD8 subsets) from the time of enrollment through teclistamab resumption and through the end-of-study. |
| Rate of infectious complications | 12 months after teclistamab discontinuation | Frequency of infectious complications from time of teclistamab discontinuation. |
Countries
United States
Contacts
Primary ContactLeonard Fiannaca, MS
Backup ContactAlfred Garfall, MD
Outcome results
None listed