Study of Iberdomide, Bortezomib, and Dexamethasone for ND-NTE MM Patients

Study Overview
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Brief Summary
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This study will evaluate efficacy and tolerability of iberdomide, weekly bortezomib and dexamethasone administered in combination.

Detailed Description
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This is a phase II, multicenter, single arm, open label study of iberdomide, weekly bortezomib and dexamethasone for upfront treatment of transplant ineligible patients with Multiple Myeloma. This study will evaluate efficacy and tolerability of iberdomide, bortezomib and dexamethasone administered in combination. The study will have an induction phase and a maintenance phase.

Official Title
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A Single Arm, Multicentre, Open Label Study of Iberdomide, Weekly Bortezomib and Dexamethasone for Transplant-ineligible, Newly Diagnosed Multiple Myeloma Patients: the BOREALIS Trial

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Iberdomide
* Drug: Bortezomib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must understand and voluntarily sign informed consent form Age ≥ 65 years at the time of signing consent Must be able to adhere to the study visit schedule and other protocol requirements. Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below: Monoclonal plasma cells in the bone marrow ≥10% and/or presence of a biopsy proven plasmacytoma Monoclonal protein present in the serum and/or urine Myeloma-related organ dysfunction (at least one of the following); i. [C] Calcium elevation in the blood (serum calcium >2.75 mmol/L or >0.25 mmol/L higher than the upper limit of normal) ii. [R] Renal insufficiency (serum creatinine >177 µmol/L) iii. [A] Anemia (hemoglobin <100 g/l or 2 g < laboratory normal) iv. [B] Lytic bone lesions or osteoporosis AND have measurable disease by protein electrophoresis analyses as defined by the following: IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥10 g/l or urine M-protein level ≥ 200 mg/24 hours IgA multiple myeloma: Serum M-protein level ≥ 5 g/l or urine M-protein level ≥ 200 mg/24 hours IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level ≥ 10 g/l or urine M-protein level ≥ 200 mg/24hours IgD multiple myeloma: Serum M-protein level ≥ 0.5 g/l or urine M-protein level ≥ 200 mg/24 hours Serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved free light chain is at least 100 mg/L Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. Females of child-bearing potential (FCBP) must have a negative serum test and register with the RevAid® program. FCBP and males must either commit to continued abstinence from heterosexual intercourse or must abide by birth control requirements as described in Appendix 1 for the Lenalidomide for the RevAid® program. Men must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy Life expectancy of ≥ 3 months. Able to take oral medications. The following laboratory results must be met within 10 days of first study drug administration: Absolute neutrophil count (ANC) ≥ 1.0 x 109/L. Growth factors cannot be given within 10 days of study drug administration. Serum AST and ALT ≤ 1.5 x upper limit of normal (ULN). Creatinine clearance ≥ 30 mL/min either directly measured via 24-hour urine collection or calculated using MDRD (Appendix 2). Platelet count ≥ 50 x 109/L. Platelet transfusions to help subjects meet eligibility criteria are not allowed within 10 days before study enrollment. Hemoglobin ≥ 80 g/L. NOTE: Laboratory results obtained during screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the investigator may opt to retest the subject and the subsequent within range screening result may be used to confirm eligibility. Exclusion Criteria: Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [i.e. less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of treatment start]). Any serious medical condition that places the patient at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, patient with unstable cardiac disease as defined by: Cardiac events such as MI within the past 6 months, NYHA heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; patients with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment. Pregnant or lactating females. Renal failure requiring hemodialysis or peritoneal dialysis. Prior history of malignancies, other than multiple myeloma, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following: Basal cell carcinoma of the skin Squamous cell carcinoma of the skin Carcinoma in situ of the cervix Carcinoma in situ of the breast Incidental histological finding of prostate cancer (TNM stage of T1a or T1b) Patients who are unable or unwillingly to undergo antithrombotic therapy. Peripheral neuropathy of ≥ grade 2 severity. Known HIV positivity or active infectious hepatitis, type A, B, or C. Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis. Plasma cell leukemia. Evidence of cardiovascular risk including any of the following: QTc interval ≥ 470 msecs. Note that the QT interval should be corrected for heart rate by Fridericia's formula (QTcF) Evidence of current clinically significant uncontrolled arrhythmias; including clinically significant ECG abnormalities; including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of screening. Class III or IV heart failure as defined by the New York Heart Association functional classification system (Appendix 3) Uncontrolled hypertension

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Iberdomide|Available as formulated capsules and administered as oral medication|
|Drug: Bortezomib|Administered as subcutaneous injection|
|Drug: Dexamethasone|Administered as oral medication|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Rate of Stringent Complete Response (sCR) transplant ineligible multiple myeloma patients. | Evaluate the rate of stringent complete response (sCR) after 4 cycles of therapy of Iber+ weekly Bd in newly diagnosed transplant ineligible multiple myeloma patients. | After 4 cycles of therapy (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Objective Response | Evaluate objective response as per IMGW criteria: progressive disease, stable disease, partial response, very good partial response, complete response and stringent complete response according to IMGW criteria. Multiple measurements will be aggregated to arrive at one reported value (e.g., weight and height will be combined to report BMI in kg/m^2). | After 4 cycles of therapy (each cycle is 28 days) |