Iberdomide Combined With Low-dose Cyclophosphamide and Dexamethasone

NCT04392037 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: HAEM-2020-1NL72835.029.202019-004604-35
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 9

Brief Summary

Evaluation of the effect iberdomide combined with low-dose cyclophosphamide and dexamethasone in patients with relapsed/refractory multiple myeloma.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (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

  up to 5 years

Secondary Outcomes (7)

• Overall response rate

  up to 5 years

• Safety and toxicity

  up to 5 years

• Overall survival

  up to 5 years

• Time to response

  up to 5 years

• Duration of response

  up to 5 years

Study Arms (1)

Iberdomide plus low-dose cyclophosphamide and dexamethasone

EXPERIMENTAL

Iberdomide 1.6mg on days 1-21 Low-dose Cyclophosphamide 50 mg on days 1-28 of each 28 day cycle Dexamethasone 40 mg once weekly (20 mg in patients aged \> 75 years)

Drug: Iberdomide plus low-dose cyclophosphamide and dexamethasone

Interventions

Iberdomide plus low-dose cyclophosphamide and dexamethasone DRUG

Iberdomide, low dose Cyclophosphamide and Dexamethason will be given until progression or unacceptable toxicity

Also known as: CC-220

Iberdomide plus low-dose cyclophosphamide and dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• 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 (See Appendix A)
• 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.
• 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 )
• 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 International Myeloma Working Group criteria.
• WHO performance 0, 1, or 2
• Life expectancy at least 3 months
• Written informed consent
• 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:
• 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.
• 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. Contraception requirements are detailed in Appendix H.
• 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.
• \* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.\]

You may not qualify if:

• 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).
• Treatment with prior iberdomide
• Non-secretory MM
• Systemic AL amyloidosis or plasma cell leukemia (\>2.0x109/L circulating plasma cells by standard differential) or Waldenstrom's macroglobulinemia
• Subject has known meningeal involvement of multiple myeloma
• Inadequate marrow reserve as defined by a platelet count \<75 x 109/L or an absolute neutrophil count \<1.0 x 109/L
• Corrected serum calcium \>13.5 mg/dL (\>3.4 mmol/L)
• 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.
• 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
• 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
• 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:

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Celgene: collaborator

Study Sites (9)

NWZ

Alkmaar, Netherlands

Location

Amsterdam UMC, location AMC

Amsterdam, Netherlands

Location

Amsterdam UMC, location VUmc

Amsterdam, Netherlands

Location

Rijnstate

Arnhem, Netherlands

Location

Amphia Ziekenhuis

Breda, Netherlands

Location

Albert Schweitzer Ziekenhuis

Dordrecht, Netherlands

Location

UMC Groningen

Groningen, Netherlands

Location

Antonius ziekenhuis

Nieuwegein, Netherlands

Location

Radboud UMC

Nijmegen, Netherlands

Location

Related Publications (1)

• Korst CLBM, Plattel W, de Kort EA, Smits F, Croockewit AJ, Levin MD, Westerman M, de Weerdt O, Nijhof IS, Wegman J, Smit N, Verkleij CPM, Mutis T, Nasserinejad K, Kerstiens R, van der Klift M, Franssen LE, de Ruijter MEM, Groen K, van der Spek E, Roeloffzen WWH, Zweegman S, van de Donk NWCJ. Iberdomide plus low-dose cyclophosphamide and dexamethasone in patients with relapsed and refractory multiple myeloma (the ICON study): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2026 Jan;13(1):e30-e40. doi: 10.1016/S2352-3026(25)00298-4.

  PMID: 41482445 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

iberdomide; Cyclophosphamide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• N.W.C.J van de Donk, Prof. MD PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Niels W.C.J. van de Donk

Model Details: Patients will be treated with iberdomide plus low-dose cyclophosphamide and dexamethasone (IberCd)

Study Record Dates

• First Submitted: May 13, 2020
• First Posted: May 18, 2020
• Study Start: February 17, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 28, 2025

Record last verified: 2025-03

Locations

NL (9)