A PHASE 3, TWO-STAGE, RANDOMIZED, MULTICENTER, OPEN-LABEL STUDY COMPARING IBERDOMIDE, DARATUMUMAB AND DEXAMETHASONE (IberDd) VERSUS DARATUMUMAB, BORTEZOMIB, AND DEXAMETHASONE (DVd) IN SUBJECTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM) (EXCALIBER-RRMM)

JRCT ID: jRCT2051210043

Registered date:01/07/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Relapsed or refractory multiple myeloma (RRMM)
• Date of first enrollment: 01/12/2022
• Target sample size: 45
• Countries of recruitment: China,Japan,South Korea,Japan,Austlaria,Japan,Austria,Japan,Belgium,Japan,Canada,Japan,Czech Rep,Japan,Denmark,Japan,Finland,Japan,France,Japan,Germany,Japan,Greece,Japan,Ireland,Japan,Italy,Japan,Netherlands,Japan,Norway,Japan,Poland,Japan,Portugal,Japan,Russia,Japan,Spain,Japan,Sweden,Japan,Switzerland,Japan,Israel,Japan,Taiwan,Japan,Turkey,Japan,UK,Japan,US,Japan
• Study type: Interventional
• Intervention(s): [IberDd] At the First Stage, Iberdomide (CC-220) 1.0 mg, 1.3 mg or 1.6 mg will be administered orally once daily for 21 consecutive days, followed by a 7-day rest period. This procedure, constituting 1 cycle of administration, will be repeated. At the Second Stage, the dose at the Second Stage established based on the assessments at the First Stage will be administered orally once daily for 21 consecutive days, followed by a 7-day rest period. This procedure, constituting 1 cycle of administration, will be repeated. Daratumumab will be injected subcutaneously at a dose of 1800 mg as daratumumab and 30000 units as vorhyaluronidase alfa every week (Days 1, 8, 15, and 22) in Cycles 1 and 2, every 2 weeks (Days 1 and 15) in Cycles 3 to 6, and every 4 weeks (Day 1) in Cycle 7 and onwards. Dexamethasone will be administered orally at a dose of 40 mg weekly (Days 1, 8, 15, and 22). [DVd] Daratumumab will be injected subcutaneously in 21-day cycles at a dose of 1800 mg as daratumumab and 30000 units as vorhyaluronidase alfa every week (Days 1, 8, and 15) in Cycles 1 to 3 and every 3 weeks (Day 1) in Cycles 4 to 8. In Cycle 9 and onwards, subcutaneous injections will be performed every 4 weeks (Day 1) in 28-day cycles. Bortezomib will be administered subcutaneously at the dose of 1.3 mg/m2 on Days 1, 4, 8, and 11 in Cycles 1 to 8. Dexamethasone will be administered orally at the dose of 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 in Cycles 1 to 8.

Outcome(s)

Primary Outcome

Progression-free survival (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 or death due to any cause, whichever occurs first

Secondary Outcome

Overall survival (OS);
Time from randomization to time of death due to any Cause
Overall response rate (ORR);
Percentage of subjects who achieve best response of partial response (PR) or better according to the IMWG Uniform Response Criteria for Multiple Myeloma
Time to response (TTR);
Time from randomization to the first documentation of response (PR or better)
Duration of response (DoR);
Time from the first documentation of response (PR or better) to the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first
Time to progression (TTP);
Time from randomization to the first documentation of PD
Time to next treatment (TTNT);
Time from randomization to the start of the next antimyeloma Treatment
Progression-free survival 2 (PFS2);
Time from randomization to progression on the next anti-myeloma treatment or death due to any cause, whichever occurs first
Safety;
Type, frequency, seriousness and severity of adverse events (AEs), and relationship of AEs to study treatment
European Organization for Research and Treatment of Cancer-Quality of Life C30 questionnaire (EORTC QLQ-C30) and European Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20);
Mean changes from baseline in subscale scores in subject-reported health related quality of life outcomes and multiple myeloma-related symptoms as measured by the EORTC QLQ-C30 and the EORTC QLQ-MY20

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Documented diagnosis of MM and measurable disease, defined as any of the following:
a. M-protein quantities >= 1g/dL by serum protein electrophoresis (sPEP) or >= 200mg/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 > 100mg/L (10mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio
2. Received 1 to 2 prior lines of anti-myeloma therapy
3. Achieved a response (partial response [PR] or better) to at least 1 prior antimyeloma regimen
4. Must have documented disease progression during or after their last antimyeloma regimen
5. 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
b. Subject did not progress while receiving CD38-directed therapy or within 60 days of last dose of therapy
c. Subject did not discontinue CD38-directed therapy due to a related AE
6. 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)
b. Subject did not progress while receiving bortezomib therapy or within 60 days of last dose of therapy
7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.

Exclude criteria

1. Any of the following laboratory abnormalities:
a. Absolute neutrophil count (ANC) < 1,000/microL. It is not permissible to administer granulocyte colony-stimulating factor (GCSF) to achieve minimum ANC levels
b. Platelet count: < 75,000/microL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 50,000/microL 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 < 8g/dL (< 4.9mmol/L)
d. Estimated glomerular filtration rate (eGFR) < 30mL/min/1.73m^2 or requiring dialysis. The eGFR can be calculated using the modified diet in renal disease (MDRD) formula
e. Corrected serum calcium > 13.5mg/dL (> 3.4mmol/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 > 3.0mg/dL for subjects with documented Gilbert's syndrome
2. Has plasma cell leukemia, Waldenstrom's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically significant amyloidosis
3. Known central nervous system involvement with MM
4. Prior therapy with iberdomide
5. 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

Related Information

• Primary Sponsor: Kimura Shunsuke
• Secondary ID(s): NCT04975997