Myeloma Multiple
Conditions
Keywords
cancer, hematology, relapse, antibody
Brief summary
The BELAMI trial is an open label, multicenter, phase 2 study for patients with MM who relapsed following BCMA-directed CAR-T cells or bispecific antibodies with a Phase Ib Safety run-in. The primary hypothesis of this study is that a combination of ADC targeting BCMA and CELMoD will be efficient for these patients.
Detailed description
CAR-T cells and bispecific antibodies targeting BCMA have been approved in the treatment of patients with multiple myeloma (MM), at late stage of disease. Data from real-world situations showed poor outcomes of patients who relapsed following these treatments. Belantamab mafodotin is an antibody-drug conjugate (ADC) targeting BCMA. Mezigdomide is a novel oral CELMoD® agent (oral cereblon-modulating) with enhanced tumoricidal and immune-stimulatory effects compared to immunomodulatory drugs. The ALGONQUIN trial demonstrated that the anti-myeloma activities of Belantamab mafodontin were significantly increased by immunomodulatory drugs. In this context, investigator aim to evaluate Belantamab mafodontin in association with Mezigdomide.
Interventions
DRUGCAR-T cells
Combination of Belantamab and Mezigdomide treatments with patients previously treated with anti-BCMA CAR-T cells (with or without bispecific antibodies)
DRUGBCMA bispecific
Combination of Belantamab and Mezigdomide treatments with patients previously treated with anti-BCMA bispecific antibodies
Sponsors
Centre Hospitalier Universitaire de Saint Etienne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase Ib/II, multicenter, open-label, parallel-group study conducted in patients with relapsed multiple myeloma after treatment with anti-BCMA bispecific antibodies and/or CAR-T cells. A minimum wash-out period of 3 months is required between the last anti-BCMA treatment and inclusion in the BELAMI study. The study includes a Phase Ib safety run-in to confirm the tolerability of the treatment combination before expanding enrollment to the full Phase II cohort.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects who are ≥ 18 years of age * Participant has a histologically or cytologically confirmed diagnosis of MM as defined by IMWG criteria * Participant has Eastern Cooperative Oncology Group (ECOG) performance status of score of 0, 1, or 2 * Participant is considered transplant ineligible or for participants with a history of autologous stem cell transplant (ASCT), ASCT was \>100 days before initiating study treatment * Participant has measurable disease with at least one of the following criteria: * Serum M protein \>0.5 g/dL (\>5 g/L), or * Urine M protein \>200 mg/24h, or * Serum free light chain (FLC) assay: Involved FLC level \>5 mg/dL (\>50 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65) * Participant is quadruple-class exposed or refractory (anti-CD38 antibody (e.g., daratumumab, isatuximab) alone or in combination, immunomodulatory agent (e.g., lenalidomide, pomalidomide), a proteasome inhibitor (e.g., bortezomib, ixazomib, carfilzomib) and BCMA-directed CAR-T cells and/or anti-BCMA bispecific antibodies) and has failed at least 3 prior lines of anti-myeloma therapies * Documented presence of BCMA. * All prior treatment related toxicities (defined by NCI-CTCAE Version 5.0) must be Grade ≤1 at the time of enrollment, except for alopecia and Grade 2 hematological, hepatic and renal laboratory values. * Participant must have adequate organ function at minimum, defined in Table 2 "adequate organ function". * Life expectancy of at least 6 months, in the opinion of the investigator * Sex and Contraceptive/Barrier Requirements * Participants must adhere to contraceptive guidelines on contraception methods in clinical studies to minimize the risk of pregnancy * Signed informed consent * Participant affiliated to or a beneficiary of a social security category
Exclusion criteria
* Patients under guardianship or curators * Patients with insufficient proficiency in French to understand the study information * Prior treatment with an anti-BCMA targeted therapy within 90 days of receiving the first dose of study drugs, or treatment with an investigational agent or approved systemic anti-myeloma therapy (including systemic steroids) within 14 days or 5 half-lives of receiving the first dose of study drugs. * A known intolerance or immediate or delayed hypersensitivity to drugs chemically related to Belantamab mafodontin or Mezigdomide or any of of the components of the study treatment. * Prior treatment with an antibody-drug conjugate. * Prior treatment with Mezigdomide. * Prior allogeneic stem cell transplant. * Any major surgery within 4 weeks before the first dose of study drug (or 2 weeks if clinically stable). Additional exception allowed for bone-stabilizing surgery after consultation with medical monitor. * Has received a live or attenuated vaccine within 30 days before the first dose of study treatment. * Participant has received plasmapheresis ≤ 7 days before the first dose of study treatment. * Presence of active renal condition (infection, requirement for dialysis, or any other condition that could affect participant's safety). * Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent, or compliance with the study procedures. * Evidence of active mucosal or internal bleeding. * Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice. * Evidence of cardiovascular risk. * Participant has malignancies other than MM are excluded, except for any other malignancy from which the participant has been disease free for \>5 years with the exception of the following noninvasive malignancies: basal or squamous cell skin carcinoma, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histological findings of prostate cancer (T1a or T1b using the tumor, nodes, and metastases clinical staging system), or prostate cancer that is curative. * Active infection requiring antibiotic, antiviral, or antifungal therapy. * Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening. * Current corneal epithelial disease, except mild punctuate keratopathy. * Contact lenses are not allowed for participants while they are receiving Belantamab mafodontin treatment. Contact lens use may be restarted after discontinuation of Belantamab mafondontin treatment, provided the eye-care specialist confirms there are no other contraindications. * Treatment with strong CYP3A4/5 modulators or Potassium-Competitive Acid Blockers or Proton Pump Inhibitors or unable to absorb oral therapies (i.e. gastric surgery). * Participant is a pregnant or lactating female. * Participant with known HIV infection is excluded, unless the specific criteria (see relative section) are met. * Patient with a presence of hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) at screening or within 3 months before first dose of study treatment should be excluded, unless the criteria described in the relative section are met. * Participant with a positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before first dose of study treatment are excluded, unless the criteria described in the relative section are met.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Year 5 | Defined as the duration from the start date of treatment to the date of either progressive disease, or death, whichever occurs first. Progressive disease will be evaluated as defined by 2016 International Myeloma Working Group (IMWG) response criteria, as data permits, and assessed by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | Year 5 | ORR, defined as CR or VGPR or PR, according to the IMWG criteria at the time of data cutoff |
| Percentage of patients achieving very good partial response (VGPR) or better, complete response (CR), and partial response (PR). | Year 5 | Percentage of VGPR or better, CR, VGPR, PR, Progression Disease defined according to the IMWG criteria at the time of data cutoff |
| Time to response (TTR) | Year 5 | Time to response |
| Duration of response (DOR) | Year 5 | Response duration |
| Overall survival (OS) | Year 5 | OS measured from the date of inclusion to the date of the subject's death. If the subject is alive or the vital status is unknown at last contact, then the subject's data will be censored at the date the subject was last known to be alive. |
| Time to progression (TTP) | Year 5 | TTP defined as time from the start date of treatment to discontinuation of therapy for any reason including death, progression, toxicity. |
| Time to next treatment (TNT) | Year 5 | TNT defined as the time from the start date of treatment to the start of the next-line treatment. |
| Time-to-treatment failure (TTF). | Year 5 | Time-to-treatment failure, defined as time from the start date of treatement to discontinuation of therapy for any reason including death, progression, toxicity. |
| Assessing therapy-related adverse events according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 6.0), particularly ocular events, to understand corneal safety and tolerability. | Year 5 | Assessing therapy-related adverse events according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 6.0), particularly ocular events, to understand corneal safety and tolerability. |
| Evaluating changes in the Ocular Surface Disease Index (OSDI) | Year 5 | Simplified OSDI (Ocular Surface Disease Index). A score of 4 or higher indicates dry eyes |
Countries
France
Contacts
CONTACTEmilie CHALAYER, MD
PRINCIPAL_INVESTIGATOREmilie CHALAYER, MD
CHU de Saint-Etienne
Outcome results
None listed