| Eligibility |
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 (< 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.
6. WHO performance 0, 1, or 2
7. Life expectancy at least 3 months
8. Written informed consent
9. 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:
1. 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.
2. 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.
10. 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.]
11. 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.
12. 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.
13. 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.
Exclusion Criteria:
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. Treatment with prior iberdomide
3. Non-secretory MM
4. Systemic AL amyloidosis or plasma cell leukemia (>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 <1.0 x 109/L
7. Corrected serum calcium >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.
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