A Study Comparing Iberdomide, Daratumumab And Dexamethasone VersusDaratumumab, Bortezomib, And Dexamethasone In Subjects With Relapsed OrRefractory Multiple Myeloma

Phase 3

Not yet recruiting

• Conditions: Multiple myeloma,

• Registration Number: CTRI/2024/01/062127
• Lead Sponsor: Celgene Corporation

Brief Summary

**This is a two-stage, multicenter, randomized, controlled, open-label, Phase 3 study comparing the efficacy and safety of IberDd versus DVd in subjects with Relapsed or Refractory Multiple Myeloma (RRMM).**



**India will participate in Stage 2 of the study.**



**Primary Objective**

·      Tocompare the efficacy of iberdomide, daratumumab and dexamethasone (IberDd) tothat of daratumumab, bortezomib and dexamethasone (DVd) in terms ofprogression-free survival (PFS) in subjects with relapsed or refractorymultiple myeloma (RRMM)

**Secondary Objective(s):**

·      Toevaluate overall survival (OS) in subjects with RRMM treated with IberDdcompared to DVd

·      Toevaluate achievement of minimal residual disease (MRD) negative status insubjects with RRMM (who achieve complete response [CR] or better) when treatedwith IberDd compared to DVd

·      Toevaluate additional efficacy parameters in subjects with RRMM treated withIberDd compared to DVd

·      Toevaluate safety of IberDd compared to DVd in subjects with RRMM

·      Toevaluate cancer-related symptoms and health-related quality of life (HRQoL)using the European Organization for Research and Treatment of Cancer – Qualityof Life C30 questionnaire (EORTC QLQ-C30) and the European Quality of LifeMultiple Myeloma Module (EORTC QLQMY20) in subjects with RRMM treated withIberDd compared to DVd

**Stage 2:**

In Stage 2 of the study, approximately 664 additionalsubjects will be randomized 1:1 between 2 treatment arms:

- Approximately 332 subjects will be randomized toreceive Treatment Arm A (IberDd)

- Approximately 332 subjects will be randomized toreceive Treatment Arm B (DVd)

The total number of subjects enrolled in Stage 2 willbe adjusted according to the number of subjects enrolled in the selectediberdomide dose level arm and in the DVd arm during Stage 1.

Overall, approximately 764 subjects are planned to beenrolled in these 2 arms considering Stage 1 and Stage 2 combined.

**Length of Study:**

The study will consist of the following consecutiveperiods: Screening, Treatment and Follow-up.

- The Screening period may not exceed a 28-day windowprior to randomization (Day -28 to Day -1).

- The Treatment period will extend from randomizationto discontinuation of all study treatment.

- The Follow-up period consists of the 28-dayFollow-up Visit, the PFS Follow-up Phase, and the Long-term Follow-up Phase.

Detailed Description

Not available

Study Timeline

• Last Update Posted: 2024-01-30
• Study Start: 2024-09-02

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 664

Inclusion Criteria

• Subjects must satisfy the following criteria to be enrolled in the study: 1.
• Subject is more than or equal to 18 years (there is no upper age limit) of age at the time of signing the informed consent form (ICF) 2.
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted 3.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements 4.
• Subject has documented diagnosis of MM and measurable disease, defined as any of the following: a.
• M-protein quantities more than or equal to 1 g/dL by serum protein electrophoresis (sPEP) or more than or equal to 200 mg/24-hour urine collection by urine protein electrophoresis (uPEP); or b.
• Light chain MM without measurable disease in serum or urine: serum-free light chain (FLC) levels > 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio 5.
• Subject has received one to 2 prior lines of anti-myeloma therapy 6.
• Subject achieved a response (partial response [PR] or better) to at least 1 prior antimyeloma regimen.
• Prior treatment with CD38-directed therapy: In Stage 1, subjects with prior CD38-directed therapy are not eligible.
• In Stage 2, prior treatment with CD38-directed therapy is permitted only if all the following are fulfilled: a.
• Best response achieved during CD38-directed-containing therapy was > PR.
• Subject did not progress while receiving CD38-directed therapy or within 60 days of last dose of therapy.
• Subject did not discontinue CD38-directed therapy due to a related AE.
• Last dose of daratumumab was more than or equal to 3 months prior to randomization.
• Prior treatment with bortezomib therapy is permitted, if all the following are fulfilled: a.
• Best response achieved during bortezomib-containing therapy was at least a minimal response (MR).
• Subject did not progress while receiving bortezomib therapy or within 60 days of last dose of therapy.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• Females of childbearing potential (FCBP) must:.

Exclusion Criteria

• The presence of any of the following will exclude a subject from enrollment: 1. Subject has any significant medical condition, including active or uncontrolled infection, presence of laboratory abnormality, or psychiatric illness that places the subject at an unacceptable risk for treatment-related complications, if he/she were to participate in the study. 2. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days for mild or asymptomatic infections or within 28 days for severe/critical illness prior to randomization. 3. Subject has any condition that confounds the ability to interpret data from the study. 4. Subject has any of the following laboratory abnormalities: a. Absolute neutrophil count (ANC) < 1,000 cells/µL. It is not permissible to administer granulocyte colony-stimulating factor (GCSF) to achieve minimum ANC levels. b. Platelet count: < 75,000 cells/µL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 50,000 cells/µL for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells. It is not permissible to transfuse subjects to achieve minimum platelet counts. c. Hemoglobin < 8 g/dL (< 4.9 mmol/L). d. Estimated glomerular filtration rate (eGFR) < 30 mL/min or requiring dialysis. The eGFR should be calculated using the Modification of Diet in Renal Disease (MDRD) formula adjusted for actual BSA e. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L). f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN). g. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert’s syndrome. 5. Subject has plasma cell leukemia, Waldenstrom’s macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically significant amyloidosis. 6. Subject has peripheral neuropathy Grade 3, Grade 4 or Grade 2 with pain. 7. Subject has gastrointestinal disease that may significantly alter the absorption of iberdomide and/or other oral study treatment. 8. Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for more than or equal to 5 years with the exception of the following noninvasive malignancies:.
• Basal cell carcinoma of the skin.
• Squamous cell carcinoma of the skin in situ (stage 0).
• Carcinoma in situ of the cervix.
• Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative 9. Subject with known central nervous system involvement with MM. 10. Subject has received immunosuppressive medication within the last 14 days of initiating study treatment. The following are exceptions to this criterion:.
• Intranasal, inhaled, topical or local corticosteroid injections (eg, intra-articular injection).
• Systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone.
• Steroids as premedication for hypersensitivity reactions 11. Subject has impaired cardiac function or clinically significant cardiac disease, including: a. Myocardial infarction within 1 year before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure New York Heart Association Class III-IV) b. Uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0 Grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities. 12. Subject received prior therapy with iberdomide. 13. Subject received any of the following: a. Plasmapheresis within the last 28 days of initiating study treatment b. Major surgery (as defined by the Investigator) within 28 days of initiating study treatment. c. Radiation therapy, other than local palliative therapy, for myeloma associated bone lesions within 14 days of initiating study treatment. d. Use of any systemic anti-myeloma drug therapy within 14 days of initiating study treatment 14. Subject received any investigational agent within 28 days.
• Subjects who are participating in other interventional trials may not participate in BMS clinical trials, except for those who have completed treatment with the prior investigational agent(s) and are currently in Long-term Follow up.
• Trial participation for subjects who have received an investigational vaccine (such as an investigational SARS-CoV-2 vaccine) will be determined by discussion between the Investigator and Sponsor Medical Monitor. 15. Subject has previously received a live vaccine within 3 months of initiating study treatment. 16. Concurrent administration of a strong inhibitor or inducer of cytochrome P450 (CYP3A4/5) (including within 14 days of initiating study treatment). 17. Subject is unable or unwilling to undergo protocol required thromboembolism or herpes zoster prophylaxis. 18. Subject has previously received allogeneic stem cell transplantation at any time during prior therapy or received autologous stem cell transplantation within 12 weeks of initiating study treatment. 19. Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal. Note that forced expiratory testing (FEV1) is required for subjects suspected of having COPD. 20. Subject has known moderate or severe persistent asthma within the last 2 years, or currently has uncontrolled asthma of any classification. 21. Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during participation in the study. 22. Subject is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, active hepatitis A, or active hepatitis C: a. Known to be seropositive for HIV. b. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR. c. Known to be seropositive for hepatitis C virus (HCV); anti-HCV antibody positive or HCV- ribonucleic acid (RNA) quantitation positive, except in the setting of a sustained virologic response (SVR), defined as aviremia at least 12 weeks after completion of antiviral therapy. 23. Subject has known allergies, hypersensitivity, or intolerance to boron or mannitol, hyaluronidase, sorbitol, corticosteroids, monoclonal antibodies or human proteins, cereblon modulating agents or their excipients 24. Subject has any contraindications to daratumumab, bortezomib or dexamethasone, per local PI. 25. Vulnerable, under judicial protection, people without freedom by administrative or judicial decision, people with psychiatric conditions without their consent, people accepted in a health or social institution for other purposes than the research, adults under legal guardianship, curatorship, and people incapable of giving consent personally.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression-free survival	Time from randomization to the first documentation of progressive disease according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma 2016 or death due to any cause, whichever occurs first.
(PFS)	Time from randomization to the first documentation of progressive disease according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma 2016 or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Time from randomization to death from any cause.
Minimal Residual Disease Negativity Rate	Sensitivity of a minimum of 1 in 10 raise to power of 5 nucleated cells by next generation flow cytometry in bone marrow aspirate for subjects who are CR or better per IMWG Uniform Response Criteria for Multiple Myeloma.
Overall response rate (ORR)	Proportion of subjects who achieve PR or better response according to the IMWG criteria
Time to response (TTR)	Time from randomization to the first documentation of response (PR or better).
Duration of response (DoR)	Time from initial documented response (PR or better) until the first date the response criteria are met for PD or death due to any cause, whichever occurs
Time to progression (TTP)	Time from randomization to the first documented disease progression.
Time to next treatment (TTNT)	Time from randomization to the start of the subject receiving any anti-myeloma treatment other than study treatment. Subjects who do not start new
Progression-free survival 2 (PFS2)	Time from randomization to documented disease progression on next-line therapy, or death from any cause, whichever occurs first.

Trial Locations

Locations (6)

Amrita Institute of Medical Sciences and Research Centre; 🇮🇳 Ernakulam, KERALA, India

Jawaharlal Institute of Postgraduate Medical Education and Research; 🇮🇳 Perambalur, TAMIL NADU, India

M.S. Ramaiah Medical College and Hospital; 🇮🇳 Bangalore, KARNATAKA, India

Mumbai Oncocare Centre (Unit of Cellcure Cancer Centre Pvt Ltd); 🇮🇳 Mumbai, MAHARASHTRA, India

Nil Ratan Sircar Medical College and Hospital; 🇮🇳 Kolkata, WEST BENGAL, India

Yashoda Hospitals; 🇮🇳 Hyderabad, TELANGANA, India

Amrita Institute of Medical Sciences and Research Centre

🇮🇳Ernakulam, KERALA, India

Dr Neeraj Sidharthan

Principal investigator

9946047464

neerajsidharthan@aims.amrita.edu