Inclusion Criteria:
1. Age ≥18 years.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status criteria of 0-2.
3. Must have archival bone marrow sample at time of diagnosis that can be used for
clonality identification for NGS if not already performed.
4. Presence of residual bone marrow minimal residual disease (MRD) positivity by
clonoSEQ® next-generation sequencing (NGS) 90-120 days post autologous stem cell
transplantation.
5. Histologically confirmed diagnosis of symptomatic multiple myeloma (patients with
multiple myeloma with secondary amyloidosis are eligible, but no amyloid treatment
will be allowed while on study).
6. Received autologous stem cell transplant as upfront therapy for myeloma (defined as
ASCT within one year of diagnosis of symptomatic MM).
7. Adequate organ function as defined below:
- - Absolute neutrophil count (ANC) ≥1,000/mm^3.
- - Platelet count ≥75,000/mm^3; platelet transfusions to help patients meet
eligibility criteria are not allowed within seven days before study enrollment.
- - Total bilirubin ≤1.5 x the upper limit of the normal range (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN.
8. Pregnancy It is not known what effects this treatment has on human pregnancy or
development of the embryo or fetus. Therefore, female subjects participating in this
study should avoid becoming pregnant, and male subjects should avoid impregnating a
female partner. Non-sterilized female subjects of reproductive age and male subjects
should use effective methods of contraception through defined periods during and after
study treatment as specified below.
Female participants: A female participant is eligible to participate if she is not
pregnant, not breastfeeding, and at least one of the following conditions applies:
- - Not a female of childbearing potential (FCBP), OR.
- - A FCBP who must have a negative serum or urine pregnancy test with a sensitivity
of at least 25 mIU/mL within 10-14 days prior to and again within 24 hours prior
to starting study medication and before each cycle of study treatment and must
either commit to continue abstinence from heterosexual intercourse or apply a
highly effective method of birth control during the intervention period and for
at least five months after the last dose of isatuximab treatment Male
participants: A male participant, even if surgically sterilized (i.e., status
post-vasectomy), must agree to use contraception during the intervention period
and for at least five months after the last dose of isatuximab treatment and
refrain from donating sperm during this period.
9. All study participants must be registered into the mandatory Revlimid REMS® program
and be willing to comply with its requirements.
10. Ability to understand a written informed consent document, and the willingness to sign
it.
Exclusion Criteria:
1. Evidence of MM disease progression any time prior to enrollment.
2. Administration or planned administration of any other concomitant chemotherapy,
immunotherapy, or any ancillary therapy that would be considered a treatment of
multiple myeloma from Day +30 post-transplant through discontinuation from study.
Local radiation therapy is allowed. Subjects may be on corticosteroids if they are
being given for disorders other than multiple myeloma (e.g., adrenal insufficiency,
rheumatoid arthritis, etc.)
3. Any serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with the completion of treatment according to this protocol.
4. Prior organ transplant requiring immunosuppressive therapy.
5. Known to be human immunodeficiency virus (HIV) positive.
6. Known to have hepatitis A, B, or C active infection. If hepatitis positive, patient
may still be per the notes below.
• Uncontrolled or active hepatitis B virus (HBV) infection: Patient with positive
HBsAg and/or HBV DNA.
Of Note:
- - Patient can be eligible if anti-HBc IgG positive (with or without positive
anti-HBs) but HBsAg and HBV DNA are negative.
- - If anti-HBV therapy in relation with prior infection was started before
initiation of investigational medicinal product, the anti-HBV therapy and
monitoring should continue throughout the study treatment period.
- - Patient with negative HBsAg and positive HBV DNA observed during screening period
will be evaluated by a specialist for start of anti-viral treatment: study
treatment could be proposed if HBV DNA becomes negative and all the other study
criteria are still met.
- - Active hepatitis C virus (HCV) infection: positive HCV RNA and negative
anti-HCV.
Of Note:
- - Patients with antiviral therapy for HCV started before initiation of
investigational medicinal product and positive HCV antibodies are eligible.
The
antiviral therapy for HCV should continue throughout the treatment period until
seroconversion.
- - Patients with positive anti-HCV and undetectable HCV RNA without antiviral
therapy for HCV are eligible.
7. Known allergy to any of the study medications, their analogues, or excipients in the
various formulations of any agent.
8. Concurrent hematologic or non-hematologic malignancy requiring treatment (other than
multiple myeloma and secondary amyloidosis).
9. Cardiac syncope, uncompensated New York Heart Association (NYHA) Class 3 or 4
congestive heart failure, myocardial infarction within the previous six months,
unstable angina pectoris, clinically significant repetitive ventricular arrhythmias
despite antiarrhythmic treatment, severe orthostatic hypotension, or clinically
important autonomic disease.
10. Major surgery within 14 days prior to start of study treatment (Note: vertebroplasty
and kyphoplasty are not considered major surgery).
11. Infection requiring systemic antibiotic therapy or other serious infection within 14
days prior to start of study treatment.
12. Participation in other clinical trials, including those where a subject received an
investigational drug within 30 days or five half-lives of the investigational drug
prior to start of study treatment, whichever is longer.
13. Any clinically significant, uncontrolled medical conditions that, in the
investigator's opinion, would expose the subject to excessive risk or may interfere
with compliance or interpretation of the study results.
14. Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized
starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine
hydrochloride, poloxamer 188, sucrose or any of the other components of study
intervention that are not amenable to premedication with steroids and H2 blockers or
would prohibit further treatment with these agents.
15. Pregnant or breastfeeding subjects.
