Iberdomide combined with low-dose cyclophosphamide and dexamethasone: ICON study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Nov 2024 → ongoing

Decision date (initial)

2024-11-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Celgene BV · Amsterdam UMC

External identifiers

EU CT number

2023-508902-66-00

EudraCT number

2019-004604-35

ClinicalTrials.gov

NCT04392037

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To evaluate progression-free survival

Secondary objectives 8

1. To investigate the efficacy of IberCd, as determined by the (s)CR+VGPR+PR rate according to the international myeloma working group (IMWG) criteria
2. To evaluate toxicity
3. To evaluate overall survival
4. To evaluate time to response
5. To evaluate duration of response
6. To evaluate Time to Second Objective Disease
7. Progression (PFS2)
8. To evaluate time to next treatment (TTNT)

Conditions and MedDRA coding

relapsed / refractory multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Age ≥ 18 years.
2. Male subjects 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 female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 90 days following the last dose of study treatment, even if he has undergone a successful vasectomy
3. All 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.
4. All male and female subjects must follow all requirements defined in the Pregnancy Prevention Program (v5.1). See Appendix H for CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials.
5. Males must agree to refrain from donating sperm while on study treatment, during dose interruptions and for at least 90 days following last dose of study treatment.
6. Subject must have documented diagnosis of multiple myeloma and have measurable disease as defined by any of the following: • Serum monoclonal paraprotein (M-protein) level ≥5 g/L (0.5 g/dL); or urine M-protein level ≥200 mg/24 hours; or serum immunoglobulin free light chain ≥100 mg/L (10 mg/dL) and abnormal serum immunoglobulin kappa lambda free light chain ratio
7. Relapsed or refractory disease. Relapse is defined as progression of disease after an initial response to previous treatment, more than 60 days after cessation of treatment. Refractory disease is defined as <50% reduction in M-protein or progression of disease during treatment or within 60 days after cessation of treatment.
8. Subject had 2-4 prior anti-myeloma regimens. (Note: Induction, bone marrow transplant with or without maintenance therapy is considered one regimen; Prior pomalidomide is allowed )
9. Subject has developed lenalidomide-refractory disease (any dose) during prior treatment with lenalidomide or a lenalidomide-containing regimen Lenalidomide-refractory MM is defined as progressive disease during therapy, no response (< PR) to prior lenalidomide-containing therapy, or progression within 60 days of discontinuation from lenalidomide-containing regimens, according to the IMWG criteria.
10. WHO performance 0, 1, or 2
11. Life expectancy at least 3 months
12. A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) and must: a. Have two negative pregnancy tests as verified by the Investigator prior to starting study treatment. She 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 two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting investigational product, during the study treatment (including dose interruptions), and for at least 28 days after the last dose of CC-220, 90 days after the last dose of cyclophosphamide, whichever is longer.
13. Written informed consent

Exclusion criteria 24

1. Subjects who previously received continuous low-dose cyclophosphamide alone or in combination with other anti-MM agents are excluded (cyclophosphamide once weekly such as in bortezomib-cyclophospahmide-dexametahsone regimen (VCD) is allowed).
2. Peripheral neuropathy of ≥grade 2.
3. Subject has received any of the following within the last 14 days of initiating IberCd: - Plasmapheresis - Major surgery (as defined by the Investigator) - Radiation therapy other than local therapy for MM associated bone lesions - Use of any systemic myeloma drug therapy
4. Subject has been treated with an investigational agent (ie, an agent not commercially available) within 28 days or 5 half-lives (whichever is longer) of initiating IberCd treatment
5. Systemic AL amyloidosis or plasma cell leukemia (>2.0x109/L circulating plasma cells by standard differential) or Waldenstrom's macroglobulinemia
6. Uncontrolled or severe cardiovascular disease (NYHA class III or IV heart failure; myocardial infarction within the last 6 months of study entry); unstable angina; unstable cardiac arrhythmias; clinically significant pericardial disease)
7. History of active malignancy during the past 3 years, except squamous cell and basal cell carcinomas of the skin and carcinoma in situ of the cervix or breast and incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is cured, or malignancy that in the opinion of the local investigator, with concurrence with the principal investigator, is considered cured with minimal risk of recurrence within 3 years.
8. Subject has previously received an allogeneic stem cell transplantation within 1 year before the date of registration and has not used immunosuppressive drugs within one month before the date of registration.
9. Treatment with prior iberdomide
10. Inadequate marrow reserve as defined by a platelet count <75 x 109/L or an absolute neutrophil count <1.0 x 109/L
11. Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L)
12. Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide, dexamethasone, or cyclophosphamide. Subject has known or suspected hypersensitivity to the excipients contained in the formulation of iberdomide, dexamethasone, or cyclophosphamide.
13. Subject has current or prior use of immunosuppressive medication within 14 days prior to the first dose of IP. The following are exceptions to this criterion: Protocol: ICON study, Version number: 4, date October 14, 2020 26 of 117 - Intranasal, inhaled, topical or local steroid injections (eg, intra-articular injection) - Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of prednisone or equivalent - Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication)
14. Subject has taken a strong inhibitor or inducer of CYP3A4/5 including grapefruit, St. John’s Wort or related products within two weeks prior to dosing and during the course of study
15. Subject known to test positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, or active hepatitis A or C
16. Non-secretory MM
17. Subject has known meningeal involvement of multiple myeloma
18. Creatinine clearance <45 ml /min or requirement of dialysis.
19. Significant hepatic dysfunction (total bilirubin >3 times normal value or transaminases > 3 times normal value), unless related to multiple myeloma
20. Subject has any concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, respiratory disease, infection, hypertension, etc.) 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
21. Subjects with gastrointestinal disease that may significantly alter the absorption of CC-220
22. Subject is known or suspected of not being able to comply with the study protocol (eg, because of alcoholism, drug dependency, or psychological disorder) or the subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments
23. Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during the participation in the study
24. Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival (PFS; i.e. time from the first dose of iberdomide-cyclophosphamide-dexamethasone to progression or death from any cause, whichever comes first)

Secondary endpoints 7

1. Overall response rate. In this analysis we will consider the best response obtained during treatment according to the international myeloma working group (IMWG) criteria
2. Safety and toxicity as defined by type, frequency and severity of adverse events as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03
3. Overall survival measured from first dose of iberdomide-cyclophosphamide-dexamethasone, to time of death from any cause. Patients still alive or lost to follow up are censored at the date they were last known to be alive.
4. Time to response defined as time from first dose of iberdomide-cyclophosphamidedexamethasone to the first objective documentation of PR or better.
5. Duration of response defined as time from documentation of tumor response to disease progression.
6. Time to second objective disease progression (PFS2) defined as time from first dose of iberdomide-cyclophosphamide-dexamethasone to 2nd disease progression or death from any cause.
7. Time to next treatment (TTNT) defined as the date from first dose of iberdomide- cyclophosphamide-dexamethasone to first day when subject receives another myeloma treatment. Subjects who do not start new myeloma therapy are censored at the last known alive date or first dose date, whichever is later.

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

Sponsor organisation

Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC

Contact name

Prof. Dr. N.W.C.J. van de Donk

Public contact point

Organisation

Amsterdam UMC

Contact name

Prof. Dr. N.W.C.J. van de Donk

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 6 files

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

Application history

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