A Study of Venetoclax in Combination With Isatuximab and Dexamethasone for Relapsed/Refractory Multiple Myeloma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
AgeNot listed
SponsorOncotherapeutics
About this trial
A phase 2 study of venetoclax in combination with isatuximab and dexamethasone for relapsed/refractory multiple myeloma patients with t(11;14)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Clonal bone marrow plasma cells >10%
Biopsy-proven bony or extramedullary plasmacytoma
Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically
Hypercalcemia: serum calcium >0.25 mmol/L (>1mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11mg/dL)
Disqualifiers
Participant has a history of intolerability to any of the study drugs
Participant has any of the following conditions: amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), known human immunodeficiency viral (HIV) infection, active hepatitis B or C infection based on blood screen tests, significant cardiovascular disease, including uncontrolled angina, severe or uncontrolled arrhythmia, recent myocardial infarction within 6 months of screening, or congestive heart failure New York Heart Association (NYHA) Class greater than or equal to 3, Major surgery within 4 weeks prior to screening, acute infections requiring parenteral therapy (antibiotic, antifungal, or antiviral) within 14 days prior to screening, uncontrolled diabetes or uncontrolled hypertension within 14 days prior to screening, any other medical condition that, in the opinion of the Investigator, would adversely affect the participant's participation in the study
Participant has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions: previous malignancy with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study
If participant had prior allogeneic stem cell transplant (SCT), participant has evidence of ongoing graft-versus-host disease (GvHD)
Trial design
Design model
Single group
Treatments tested in this trial
Venetoclax
DrugAll subjects in Dose Level 0 will receive 1) venetoclax, PO, at 400 mg every day (QD) on Days 1-28 of a 28-day cycle, 2) dexamethasone 40 mg IV, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle; and 3) isatuximab 10mg/kg, IV, on Days 1, 8, 15, and 22 of the first 28-day cycle, and then Days 1 and 15 during subsequent 28-day cycles.
Treatment groups
39 Participants
are divided into 1 treatment groupGroup A: open-labelExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of Treatment-Emergent Adverse Events [Safety]
Safety will be measured by counting the occurrence of adverse events throughout the study, graded via Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 criteria
Time frame
[Time Frame: 54 months]2
Overall response rate (ORR) as a measure of efficacy
To assess the overall response rate (ORR = CR + VGPR + PR)
Time frame
[Time Frame: 54 months]3
Clinical benefit rate (CBR) as a measure of efficacy
(CBR = CR + VGPR + PR + MR)
Time frame
[Time Frame: 54 months]Secondary outcomes
1
Assessment of the time to progression as a measure of efficacy (TTP)
Time to progression, defined as the time (in months) from the initiation of therapy to progressive disease.Time to progression, defined as the time (in months) from the initiation of therapy to progressive disease.
Time frame
[Time Frame: 54 months]2
Progression Free Survival (PFS)
Progression-free survival will be measured in months as the time from initiation of therapy to progressive disease or death from any cause, whichever occurs first
Time frame
[Time Frame: 54 months]3
Time to first response (TTFR)
Time to first response (TTFR), defined as the time from the initiation of therapy to the first evidence of confirmed clinical benefit defined as \> MR including patients who achieved a CR, VGPR, PR, or MR
Time frame
[Time Frame: 54 months]4
Duration of response (DOR)
Duration of response, defined as the time (in months) from the first response to progressive disease
Time frame
[Time Frame: 54 months]Other outcomes
1
Biomarker (sBCMA) screening for all patients
In this study, we will assess the serum levels of a new serum biomarker for MM, BCMA. It is a tumor necrosis factor receptor family member that is expressed on the surface of normal and malignant B-cells, including MM cells. Serum (s)BCMA levels have been shown to be elevated among MM patients with progressive disease and low among those responding to treatment. In addition to correlating with clinical status, baseline sBCMA levels have been shown to predict PFS and OS. Changes in its levels also mirror those that occur in M protein levels.
Time frame
[Time Frame: 54 months]Sponsors and contacts
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Source ClinicalTrials.gov