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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 04/16/2021.

Iberdomide Combined With Low-dose Cyclophosphamide and Dexamethasone

Clinicaltrials.gov identifier NCT04392037

Recruitment Status Not yet recruiting

First Posted May 18, 2020

Last update posted October 22, 2020

Study Description

Brief summary:

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

  • Condition or Disease:Multiple Myeloma
  • Intervention/Treatment: Drug: Iberdomide plus low-dose cyclophosphamide and dexamethasone
  • Phase: Phase 2
Detailed Description

Novel drugs such as lenalidomide (an immunomodulatory drug; IMiD) have markedly improved the prognosis of multiple myeloma patients. Over the recent years, lenalidomide is increasingly used as part of first line therapy, typically until the development of progressive disease. These lenalidomide-refractory patients can be treated with several regimens. However, these regimens frequently contain proteasome inhibitors which are associated with neuropathy (bortezomib) or cardiovascular complications (carfilzomib). These proteasome inhibitors also need to be administered subcutaneously or intravenously in the hospital, once or twice per week. Also these regimens have limited efficacy in lenalidomide-refractory patients. This indicates that there is still an unmet medical need for new treatment options for patients who develop lenalidomide-refractory disease. These new treatment regimens should be active and safe without induction of neuropathy or cardiovascular side effects Moreover, an all oral regimen is frequently preferred by patients. Iberdomide plus low-dose cyclophosphamide and dexamethasone Available data indicates that the Cereblon E3 ligase modifying drug (CELMoD) iberdomide (CC220) is pharmacologically distinct from lenalidomide and pomalidomide with a higher potency against Cereblon, leading to differentiated antitumor and immunostimulating effects. Since iberdomide plus dexamethasone is active and well-tolerated in heavily pretreated patients including those with lenalidomide/pomalidomide-refractory disease, this two-drug regimen forms a new platform to which other agents can be added. The combinations of bortezomib, carfilzomib, or daratumumab plus iberdomide and dexamethasone are currently being evaluated. Investigators have shown that low-dose cyclophosphamide can be effectively combined with the IMiDs lenalidomide and pomalidomide. These combinations are effective and are well-tolerated. To address the unmet medical need for new treatment options for lenalidomide-refractory MM patients, the investigators aim at further improving the efficacy of IMiD/CELMoD plus dexamethasone combination therapy in terms of response and progression-free survival, by adding low-dose cyclophosphamide to the iberdomide-dexamethasone backbone (IberCd). This all-oral regimen will be tested in a lenalidomide-refractory patient population with 2-4 prior lines of therapy. The goal of this trial is to investigate the efficacy and safety of the IberCd combination in multiple myeloma patients who have refractory disease or a relapse after prior treatment with lenalidomide. Besides, various correlative studies will be performed during this trial including immune monitoring.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 60 participants
  • Intervention Model: Single Group Assignment
  • Intervention Model Description: Patients will be treated with iberdomide plus low-dose cyclophosphamide and dexamethasone (IberCd)
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Phase 2 Study of CC220 (Iberdomide) Combined With Low-dose Cyclophosphamide and Dexamethasone in Relapsed/Refractory Multiple Myeloma (IberCd): ICON Study
  • Estimated Study Start Date: November 2020
  • Estimated Primary Completion Date: November 2023
  • Estimated Study Completion Date: November 2023
Arms and interventions
Arm Intervention/treatment
Experimental: Iberdomide plus low-dose cyclophosphamide and dexamethasone
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
Iberdomide, low dose Cyclophosphamide and Dexamethason will be given until progression or unacceptable toxicity
Outcome Measures
  • Primary Outcome Measures: 1. Progression free survival [ Time Frame: up to 5 years ]
    PFS; i.e. time from the first dose of iberdomide-cyclophosphamide-dexamethasone to progression or death from any cause, whichever comes first
  • Secondary Outcome Measures: 1. Overall response rate [ Time Frame: up to 5 years ]
    In this analysis the investigators will consider the best response obtained during treatment according to the international myeloma working group (IMWG) criteria
  • 2. Safety and toxicity [ Time Frame: up to 5 years ]
    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 [ Time Frame: up to 5 years ]
    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 [ Time Frame: up to 5 years ]
    defined as time from first dose of iberdomide-cyclophosphamide-dexamethasone to the first objective documentation of PR or better.
  • 5. Duration of response [ Time Frame: up to 5 years ]
    defined as time from documentation of tumor response to disease progression.
  • 6. Time to second objective disease progression (PFS2) [ Time Frame: up to 5 years ]
    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) [ Time Frame: up to 5 years ]
    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.
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

1. Age ≥ 18 years.

2. 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)

3. 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. 4. 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 ) 5. 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 (2.0x109/L circulating plasma cells
by standard differential) or Waldenstrom's macroglobulinemia

5. Subject has known meningeal involvement of multiple myeloma

6. Inadequate marrow reserve as defined by a platelet count <75 x 109/L or an absolute neutrophil count 13.5 mg/dL (>3.4 mmol/L)

8. 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.

9. 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

10. 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

11. 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:

- 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)

12. 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

13. Creatinine clearance <30 ml/min or requirement of dialysis. 14. 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) 15. Significant hepatic dysfunction (total bilirubin ≥ 3 times normal value or transaminases ≥ 3 times normal value), unless related to myeloma 16. 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. 17. Subject known to test positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, or active hepatitis A or C 18. Peripheral neuropathy of ≥grade 2. 19. Subjects with gastrointestinal disease that may significantly alter the absorption of CC-220 20. 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. 21. 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. 22. Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become pregnant during the participation in the study 23. Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis 24. 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.

Contacts and Locations
Contacts

Contact: N.W.C.J van de Donk, Prof. MD PhD +31204444444 n.vandedonk@amsterdamumc.nl

Contact: C.L.B.M. Korst, MD +31204444444 c.korst@amsterdamumc.nl

Locations
Show 11 Study Locations
Sponsors and Collaborators

VU University Medical Center

Celgene

Investigators

Principal Investigator: N.W.C.J van de Donk, Prof. MD PhD Amsterdam UMC, location VUmc

More Information
  • Responsible Party: VU University Medical Center
  • ClinicalTrials.gov Identifier: NCT04392037 History of Changes
  • Other Study ID Numbers: HAEM-2020-1, NL72835.029.20, 2019-004604-35
  • First Posted: May 18, 2020 Key Record Dates
  • Last Update Posted: October 22, 2020
  • Last Verified: October 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Undecided
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Product Manufactured in and Exported from the U.S.: Yes
  • Additional relevant MeSH terms: Neoplasms, Plasma Cell Multiple Myeloma