A phase 2 study of CC220 (iberdomide) combined with low-dose cyclophosphamide and dexamethasone in relapsed/refractory multiple myeloma (IberCd): ICON STUDY

1. Age >= 18 years.

2. Subject must have documented diagnosis of multiple myeloma and have
measurable disease as defined by any of the following:
o 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:
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.
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.

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.