Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05272826
Other study ID # CMRG 010
Secondary ID
Status Not yet recruiting
Phase Phase 2
First received
Last updated
Start date October 2024
Est. completion date March 2031

Study information

Verified date April 2024
Source Canadian Myeloma Research Group
Contact Aniba Khan
Phone 4164779849
Email cmrg@cmrg.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study will evaluate efficacy and tolerability of iberdomide, bortezomib, dexamethasone and isatuximab on demand administered in combination.


Description:

This is a phase II, multicenter, single arm, response adapted, open label study of iberdomide, weekly bortezomib and dexamethasone (IberBd) for upfront treatment of transplant ineligible patients with Multiple Myeloma. Isatuximab will be added to treatment regimen for those who do not attain VGPR after 4 cycles or MRD negativity at 4 cycles of IberBd. This study will have an Induction phase (cycle 1-4), an Intensification phase (cycle 5-8) and a Maintenance phase (cycle 9 onwards).


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 75
Est. completion date March 2031
Est. primary completion date March 2028
Accepts healthy volunteers No
Gender All
Age group 65 Years and older
Eligibility Inclusion Criteria: 1. Must understand and voluntarily sign informed consent form 2. Age = 65 years at the time of signing consent 3. Must be able to adhere to the study visit schedule and other protocol requirements. 4. Previously untreated, transplant ineligible, symptomatic multiple myeloma as defined by the criteria below. Both criteria a and b must be met: 1. Clonal bone marrow plasma cells =10% or biopsy-proven bony or extramedullary plasmacytoma 2. Any one or more of the following myeloma defining events (MDE): I. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: i.Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL) ii. Renal insufficiency: creatinine clearance 177 µmol/L (>2 mg/dL) iii. Anemia: hemoglobin value of >2 g/dL below the lower limit of normal, or a hemoglobin value <10g/dL iv. Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT) II. Biomarker criteria or MDE: i. Clonal bone marrow plasma cell percentage = 60% ii. Involved: uninvolved serum free light chain (FLC) ratio =100 (involved FLC level must be =100 mg/L) iii. > 1 focal lesions on magnetic resonance imaging (MRI) studies (at least 5 mm in size) 5. Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. 6. Females of child-bearing potential (FCBP) must have a negative serum test and follow the guidelines in the pregnancy prevention program. FCBP and males must either commit to continued abstinence from heterosexual intercourse or must abide by birth control requirements as described in Appendix 9 for the pregnancy prevention program. 7. 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 as described in Appendix 9 of the pregnancy prevention program. 8. Life expectancy of = 3 months. 9. Able to take oral medications. 10. The following laboratory results must be met within 10 days prior to first study drug administration: 1. Absolute neutrophil count (ANC) = 1.0 x 109/L. Growth factors cannot be given within 10 days of study drug administration. 2. Serum AST and ALT = 1.5 x upper limit of normal (ULN). 3. Creatinine clearance = 30 mL/min either directly measured via 24-hour urine collection or calculated using MDRD (Appendix 1). 4. Platelet count = 50 x 109/L. Platelet transfusions to help subjects meet eligibility criteria are not allowed within 10 days before study enrollment. 5. Hemoglobin = 80 g/L. Exclusion Criteria: 1. 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]). 2. 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. 3. Pregnant or lactating females. 4. Renal failure requiring hemodialysis or peritoneal dialysis. 5. Prior history of malignancies, other than multiple myeloma, unless the patient has been free of the disease for = 3 years. Exceptions include the following: 1. Basal cell carcinoma of the skin 2. Squamous cell carcinoma of the skin 3. Carcinoma in situ of the cervix 4. Carcinoma in situ of the breast 5. Incidental histological finding of prostate cancer (TNM stage of T1a or T1b) 6. Patients who are unable or unwilling to undergo antithrombotic therapy. 7. Peripheral neuropathy of = grade 2 severity. 8. Known HIV positivity or active infectious hepatitis, type A, B, or C. 9. Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis. 10. Plasma Cell Leukemia 11. Evidence of cardiovascular risk including any of the following: 1. QTc interval = 470 msecs. Note that the QT interval should be corrected for heart rate by Fridericia's formula (QTcF) 2. Evidence of current clinically significant uncontrolled arrhythmias; including clinically significant ECG abnormalities; including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block. 3. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of screening. 4. Class III or IV heart failure as defined by the New York Heart Association functional classification system (Appendix 2) 5. Uncontrolled hypertension 12. Patients with hypersensitivity to boron or any of its excipients or to the active substance of Iberdomide or its excipients 13. Patients requiring strong inhibitors or inducers of CYP3A4/5. See Appendix 10 for a list of these drugs 14. Any concurrent severe and/or uncontrolled medical condition or psychiatric disease that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study or that confounds the ability to interpret data from the study. 15. Patients that have had severe acute respiratory syndrome coronavirus 2 infection within 14 days for mild or asymptomatic infections or 28 days for severe/critical illness prior to initiating study treatment. 16. Patients that have undergone major surgery (as defined by the investigator) within 28 days of initiating study treatment. 17. Active systemic infection that is likely to interfere with the study procedures or results or that, in the opinion of the investigator, would constitute a hazard for participating in this study. 18. Patients with a gastrointestinal disease that may significantly alter the absorption of iberdomide 19. Patients that have received a live vaccine within 3 months of initiating study treatment.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Iberdomide
Available as formulated capsules and administered as oral medication
Bortezomib
Administered as subcutaneous injection
Dexamethasone
Administered as oral medication
Isatuximab
Administered as subcutaneous injection

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Canadian Myeloma Research Group

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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)
See also
  Status Clinical Trial Phase
Recruiting NCT05027594 - Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02412878 - Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma Phase 3
Completed NCT01947140 - Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies Phase 1/Phase 2
Recruiting NCT05971056 - Providing Cancer Care Closer to Home for Patients With Multiple Myeloma N/A
Recruiting NCT05243797 - Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation Phase 3
Active, not recruiting NCT04555551 - MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma Phase 1
Recruiting NCT05618041 - The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies N/A
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Recruiting NCT03412877 - Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer Phase 2
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Recruiting NCT03570983 - A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion Phase 2
Completed NCT03665155 - First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody Phase 1/Phase 2
Terminated NCT03399448 - NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells) Phase 1
Completed NCT02812706 - Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients Phase 1/Phase 2
Active, not recruiting NCT05024045 - Study of Oral LOXO-338 in Patients With Advanced Blood Cancers Phase 1
Active, not recruiting NCT03792763 - Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients Phase 2
Active, not recruiting NCT03989414 - A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM) Phase 1/Phase 2
Withdrawn NCT03608501 - A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation Phase 2
Recruiting NCT04537442 - Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02546167 - CART-BCMA Cells for Multiple Myeloma Phase 1