A clinical study that compares a treatment with Iberdomide, Daratumumab and Dexamethasone against a treatment with Daratumumab, Bortezomib, and Dexamethasone in patients with a non-responsive or progressive blood cancer called Multiple Myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Jun 2022 → ongoing

Decision date (initial)

2024-08-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Celgene Corporation

External identifiers

EU CT number

2024-510800-35-00

EudraCT number

2020-000431-49

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenomic, Pharmacokinetic, Pharmacodynamic, Safety, Therapy

To compare the efficacy of iberdomide (also known as BMS-986382), daratumumab and dexamethasone (IberDd) to that of daratumumab, bortezomib and dexamethasone (DVd) in subjects with relapsed or refractory multiple myeloma (RRMM) in terms of minimal residual disease (MRD) negative CR at any time, and progression-free survival (PFS)

Secondary objectives 1

1. In Stage 1, to determine the dose of iberdomide in combination with dexamethasone and daratumumab to continue in Stage 2 of the study In Stage 1, to assess the PK of iberdomide in combination with daratumumab and dexamethasone To evaluate overall survival in subjects with RRMM treated with IberDd compared to DVd To evaluate the sustainability of MRD negativity in subjects with RRMM treated with IberDd compared to DVd To evaluate additional efficacy parameters in subjects with RRMM treated with IberDd compared to DVd To evaluate safety of IberDd compared to DVd in subjects with RRMM To evaluate cancer-related symptoms and health-related quality of life (HRQoL) using the European Organization for Research and Treatment of Cancer – Quality of Life C30 questionnaire (EORTC QLQ-C30) and the European Quality of Life Multiple Myeloma Module (EORTC QLQ-MY20) in subjects with RRMM treated with IberDd compared to DVd

Conditions and MedDRA coding

Relapsed or Refractory Multiple Myeloma (RRMM)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 1.Subject is ≥ 18 years of age at the time of signing the ICF.
2. 2.Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
3. 3.Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. 4.Subject has documented diagnosis of MM and measurable disease, defined as any of the following: a.M-protein quantities ≥ 1 g/dL by sPEP or ≥ 200 mg/24-hour urine collection by uPEP; or b.Light chain MM without measurable disease in serum or urine: serum FLC levels ≥ 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio
5. 5.Subject has received one to 2 prior lines of anti-myeloma therapy.
6. 6.Subject achieved a response (PR or better) to at least 1 prior anti-myeloma regimen.
7. 7.Subject must have documented disease progression during or after their last anti-myeloma regimen.
8. 8. Prior treatment with CD38-directed therapy: In Stage 1, subjects with prior CD38-directed- containing 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. 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. d.Last dose of daratumumab was ≥ 3 months prior to randomization.
9. 9.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.
10. 10.Subject has an ECOG performance status score of 0, 1 or 2.
11. 11. Individuals of childbearing potential (IOCBP) must: a.Have two negative pregnancy tests as verified by the Investigator prior to starting study treatment. They must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact. b.Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, 2 forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting study treatment, during the study treatment (including dose interruptions), and for at least 28 days after the last dose of iberdomide, 3 months after the last dose of daratumumab or 7 months after the last dose of bortezomib, whichever is longest.
12. 12. Individuals assigned male at birth must: a. Practice true abstinence (which must be reviewed on a monthly basis and source documented) or agree to use a condom during sexual contact with a pregnant partner or an individual of childbearing potential while participating in the study, during dose interruptions and for at least 28 days after the last dose of iberdomide, 3 months after the last dose of daratumumab, or 4 months after the last dose of bortezomib, whichever is longer even if he has undergone a successful vasectomy. Contraception requirements are detailed in APPENDIX E and local PI of bortezomib and daratumumab
13. 13. Male (as assigned at birth) subjects must agree to refrain from donating sperm while receiving iberdomide, during dose interruptions and for at least 28 days following last dose of iberdomide, 3 months after the last dose of daratumumab or 4 months after the last dose of bortezomib whichever is later.
14. 14.Subjects must agree to refrain from donating blood while on study treatment, during dose interruptions and for at least 28 days following the last dose of study treatment.
15. 15. All subjects must follow all requirements defined in the Pregnancy Prevention Program (v8.0). See APPENDIX E and local PI of bortezomib and daratumumab (see current version of PI, SmPC, or equivalent document for the specific country/region).

Exclusion criteria 25

1. 1.Subject has any significant medical condition
2. 2. Coronavirus Disease 2019 (COVID-19) within 7 days for mild or asymptomatic infections or 14 days for moderate/severe infections prior to initiating study treatment. A longer duration may be needed based on the investigator’s clinical judgment.
3. 3.Subject has any condition that confounds the ability to interpret data from the study.
4. 4.Subject has any of the following laboratory abnormalities: a.ANC <1,000 cells/µL. It is not permissible to administer GCSF to achieve minimum ANC levels. b. Platelet count: < 50,000 cells/µL. It is not permissible to transfuse subjects to achieve minimum platelet counts c.Hemoglobin <8 g/dL (<4.9 mmol/L) d.eGFR <30 mL/min or requiring dialysis. e.Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L). f.Serum AST or ALT >2.5 × ULN g.Serum total bilirubin >1.5 × ULN or >3.0 mg/dL for subjects with documented Gilbert's syndrome.
5. 5.Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia or POEMS syndrome, or clinically significant amyloidosis
6. 6.Subject has peripheral neuropathy Grade 3, 4 or 2 with pain.
7. 7.Subject has gastrointestinal disease that may significantly alter the absorption of iberdomide and/or other oral study treatment.
8. 8.Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥3 years with the exception of some noninvasive malignancies.
9. 9.Subject with known central nervous system involvement with MM.
10. 10.Subject has received immunosuppressive medication within the last 14 days of initiating study treatment .
11. 11.Subject has impaired cardiac function or clinically significant cardiac disease.
12. 12.Subject received prior therapy with iberdomide.
13. 13.Subject received any of the following a.Plasmapheresis within the last 28 days of initialting study treatment b.Major surgery within 28 days of initialting study treatment c.Radiation therapy, other than local palliative therapy, for myeloma associated bone lesions within 14 days of initialting study treatment d.Use of any systemic anti-myeloma drug therapy within 14 days of initialting study treatment
14. 14.Subject received any investigational agent within 28 days.
15. 15.Subject has previously received a live vaccine within 3 months of of initialting study treatment.
16. 16.Concurrent administration of a strong inhibitor or inducer of CYP450 (including within 14 days of initialting study treatment).
17. 17.Subject is unable or unwilling to undergo protocol required thromboembolism or herpes zoster prophylaxis.
18. 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 initialting study treatment.
19. 19.Subject has known COPD with a FEV1 <50% of predicted normal.
20. 20.Subject has known moderate or severe persistent asthma within the last 2 years, or currently has uncontrolled asthma of any classification.
21. 21.Subject is an individual of childbearing potential who is pregnant, nursing or breastfeeding, or who intends to become pregnant during participation in the study.
22. 22.Subject is positive for human immunodeficiency virus, chronic or active hepatitis B, A or C.
23. 23.Subject has prior history of systemic or clinically significant allergies, hypersensitivity, or intolerance to boron or mannitol, hyaluronidase, sorbitol, corticosteroids, monoclonal antibodies or human proteins, cereblon modulating agents or their excipients or known sensitivity to mammalian-derived products.
24. 24.Subject has any contraindications to daratumumab, bortezomib or dexamethasone, per local PI.
25. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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 2016 or death due to any cause, whichever occurs first.
2. Minimal Residual Disease (MRD) negative CR at any time: Achievement of MRD negativity defined as less than 1 in 10^5 nucleated cells (by next generation flow cytometry) in bone marrow aspirate for subjects who achieve CR or better at any time after randomization

Secondary endpoints 1

1. Recommended iberdomide dose for Stage 2, based on the totality of safety, efficacy, PK and PD data; In Stage 1, PK of iberdomide; Overall survival, Sustainability of MRD negativity; Overall response; Time to response; Duration of response; Time to progression; Time to next treatment; Progression-free survival 2; Safety; EORTC QLQ-C30 and EORTC QLQ-MY20

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene Corp.

Sponsor organisation

Celgene Corp.

Address

Route 206 And Province Line Road

City

Princeton

Postcode

08543-4000

Country

United States

Scientific contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Public contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Third parties 13

Locations

16 EU/EEA countries · 78 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 152 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications