Inclusion Criteria:
1. Patient has signed an informed consent form (ICF) indicating that he or she
understands the purpose of the procedures required for the study and are willing to
participate in the study. Patients must be willing and able to adhere to the
prohibitions and restrictions specified in this protocol, as referenced in the ICF.
2. Male or female patients aged 18 years or older at the time of the ICF signature.
3. Patients who have received ONLY one prior line of anti-myeloma therapy, which included
lenalidomide (at least 2 cycles, either alone or in combination) and a proteasome
inhibitor (e.g. bortezomib, carfilzomib, ixazomib). Patients must have achieved at
least a response of MR or better based on the investigator's determination of response
as defined by the IMWG criteria.
Note:
An induction treatment followed by ASCT and consolidation/maintenance will be
considered as one line of treatment.
4. Patients with a documented diagnosis of MM and with current evidence of measurable
disease defined as:
- - Serum monoclonal protein (M-protein) level ≥0.5 g/dL, measured using serum
protein electrophoresis (SPEP) and/or.
- - Urine M-protein level ≥200 mg/24 hours, measured using urine protein
electrophoresis (UPEP), or.
- - Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin
kappa lambda free light chain ratio.
5. Patients must have documented evidence of PD, based on the investigator's
determination of response as defined by the IMWG criteria, on or after the last line
of treatment.
6. Adequate bone marrow and hepatic function as defined by ALL the laboratory criteria:
- - Absolute Neutrophil Count (ANC) ≥1.0 x 109/L; GCSF administration is not allowed
to reach this level.
- - Hemoglobin level ≥7.5 g/dL (≥4.65 mmol/L);
- Platelet count ≥75 x 109/L in patients in whom <50% of bone marrow nucleated
cells are plasma cells OR Platelet count ≥50 x 109/L in patients in whom ≥50% of
bone marrow nucleated cells are plasma cells; [transfusions are not permitted to
reach this level]
- Alanine aminotransferase (ALT) level ≤2.5 x ULN.
- - Aspartate aminotransferase (AST) level ≤2.5 x ULN.
- - Total bilirubin level ≤1.5 x ULN (except for Gilbert Syndrome: direct bilirubin
≤1.5 x ULN)
- Creatinine clearance ≥30 mL/min; calculated using Cockcroft Gault.
- - Serum calcium corrected for albumin ≤14.0 mg/dL (≤3.5 mmol/L), or free ionized
calcium ≤ 6.5 mg/dL (≤1.6 mmol/L)
7.
Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2. 8. For patients experiencing toxicities resulting from previous therapy, the toxicities
must be resolved or stabilized to ≤ Grade 1.
Exclusion Criteria:
1. Previous therapy with any anti-CD38 monoclonal antibody.
2. Previous exposure to pomalidomide.
3. Patient has received anti-myeloma treatment within two weeks or five pharmacokinetic
half-lives of the treatment, whichever is longer, before Cycle 1, Day 1 (C1D1). The
only exception is emergency use of a short course of corticosteroids (the equivalent
of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment before
C1D1.
4. Previous allogeneic stem cell transplant or autologous stem cell transplantation
(ASCT) within 12 weeks before C1D1.
5. History of malignancy (other than MM) within three years before C1D1 (exceptions are
squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or
breast, or other non-invasive lesions that in the opinion of the investigator, with
concurrence with the Sponsor's medical monitor, is considered cured with minimal risk
of recurrence within three years).
6. Clinical signs of meningeal involvement of MM.
7. Clinically significant cardiac disease, including:
1. Myocardial infarction within six months before C1D1, or unstable or uncontrolled
condition (e.g., unstable angina, congestive heart failure, New York Heart
Association Class III-IV).
2. Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] Grade
3 or higher) or clinically significant electrocardiogram (ECG) abnormalities.
3. Electrocardiogram showing a baseline QT interval as corrected QTc >470 msec.
8. Known:
1. Active hepatitis A. 2. To be seropositive for hepatitis B (defined by a positive test for hepatitis B
surface antigen [HBsAg]). Patients with resolved infection (i.e., patients who
are positive for antibodies to hepatitis B core antigen [antiHBc] and/or
antibodies to hepatitis B surface antigen [antiHBs]) must be screened using
real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV)
DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Patients with
serologic findings suggestive of HBV vaccination (antiHBs positivity as the only
serologic marker) AND a known history of prior HBV vaccination, do not need to be
tested for HBV DNA by PCR.
3. To be seropositive for hepatitis C (defined by a positive test for Hepatitis C
virus (HCV) antibodies. A positive HCV antibody test should be confirmed by a HCV
RNA test. EXCEPTION: Patients in the setting of a sustained virologic response,
defined as aviremia at least 12 weeks after completion of antiviral therapy, are
not excluded).
9. Known to be seropositive for human immunodeficiency virus (defined by positive testing
for human immunodeficiency virus (HIV) antibodies).
10. Gastrointestinal disease that may significantly alter the absorption of pomalidomide.
11. Patient has plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard
differential) or Waldenström's macroglobulinemia or POEMS syndrome (polyneuropathy,
organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.
12. Any concurrent medical or psychiatric condition or disease (e.g., active systemic
infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that
is likely to interfere with the study procedures or results or that, in the opinion of
the investigator, would constitute a hazard for participating in this study.
13. Ongoing ≥Grade 2 peripheral neuropathy.
14. Patient had ≥Grade 3 rash during prior therapy.
15. Patient has had major surgery within two weeks before C1D1, or has not fully recovered
from an earlier surgery, or has a surgery planned during the time the patient is
expected to participate in the study or within two weeks after the last dose of study
drug administration. Note: patients with planned surgical procedures to be conducted
under local anesthesia may participate. Kyphoplasty or vertebroplasty are not
considered major surgery.
16. Patient has known allergies, hypersensitivity, or intolerance to any of the study
drugs, monoclonal antibodies, human proteins, or their excipients (refer to isatuximab
IB) or known sensitivity to mammalian-derived products.
17. Patient was vaccinated with live vaccines within four weeks prior to C1D1.
18. Pregnant or nursing women.
19. a. Females of childbearing potential (FCBP) unwilling to prevent pregnancy with the
use of two reliable methods of contraception for ≥4 weeks before the start of study
treatment, during treatment (including dose interruptions), and up to five months
following the last dose of isatuximab or three months following the last dose of the
rest of the study treatment, whichever is longer. This includes one highly effective
form of contraception (tubal ligation, intrauterine device, hormonal [birth control
pills, injections, hormonal patches, vaginal rings or implants] or partner's
vasectomy) and one additional effective contraceptive method (male latex or synthetic
condom, diaphragm, or cervical cap).
b. FCBP who are unwilling or unable to be tested for pregnancy: a) before study
treatment initiation, b) weekly during 1st month of treatment and then prior to each
treatment cycle administration or c) every two weeks in case of irregular menstrual
cycles, and d) up to five months following the last dose of isatuximab or three months
following the last dose of the rest of the study treatment, whichever is longer.
20. Male participants who refuse to practice true abstinence or use a condom during sexual
contact with a pregnant female or an FCBP while participating in the study, during
dose interruptions and at least five months following the last dose of isatuximab or
three months following the last dose of the rest of the study treatment, whichever is
longer, even if he has undergone a successful vasectomy.
Note 1: an FCBP is a female who: 1) has achieved menarche at some time 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).
Note 2: True abstinence is acceptable when this is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of contraception.
