Inclusion Criteria:
1. Diagnosis of newly-diagnosed multiple myeloma (NDMM) per International Myeloma Working
Group (IMWG) criteria documented initially prior to induction treatment.
2. Documentation of having received a triplet or quadruplet based initial combination
therapy containing at least two of the following: Immunomodulatory drug (IMiD),
proteosome inhibitor (PI), and/or anti-cluster of differentiation 38 (anti-CD38).
3. Documentation of attaining a best response of very good partial response (VGPR) or
better but MRD+ (sensitivity: ≤10^-5) after at least 4 cycles of combination therapy.
Note: Patients who at baseline prior to initial combination therapy did not have IMWG
evaluable disease and therefore a response assessment of VGPR was unable to be made
but currently have residual MM by M-protein and/or involved light chains and/or MRD
positivity may enroll. Also, patients who have no apparent bone marrow (BM) residual
disease but rather extramedullary disease as evidenced by positron emission tomography
(PET)/computed tomography (CT) may enroll.
4. Age ≥18 years.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1. Patients with
ECOG 2 solely due to local symptoms of myeloma (eg, pain) may be allowed after
discussion with the PI (APPENDIX A).
6. Adequate organ function, which is defined as follows:
Absolute neutrophil count (ANC) ≥1,000 cells/microliter (mcL) (unless patient
has ethnic/cyclic neutropenia or if neutropenia is thought to be due to MM)
Platelets ≥50,000 platelets/mcL.
Hemoglobin ≥8 g/dL (transfusions permitted)
Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) or direct bilirubin
≤ ULN for patients with total bilirubin levels > 1.5 ULN (except patients with
Gilbert's syndrome who must have a total bilirubin of <3 X ULN)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
(SGOT)) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase
(SGPT)) ≤ 2.5 X ULN.
Serum creatinine ≤ 1.5 X ULN (except if due to myeloma) or estimated
glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 (note that measured
glomerular filtration rate [GFR], ie, 24-hour urine, can also be used) based on
institutional standard.
Female patients of childbearing potential must have a negative serum pregnancy
test at Screening. Female patients of childbearing potential and fertile male
patients who are sexually active with a female of childbearing potential must use
highly effective methods of contraception throughout the study and for 6 months
following the last dose of study treatment. For more information on contraception
requirements, please refer to Section 4.11.
Willing and able to provide written informed consent in accordance with
federal, local, and institutional guidelines. The patient must provide informed
consent prior to the first screening procedure. For more information on the
informed consent process, please refer to Section 15.1.
7. Willing and able to comply with clinic visits and study-related procedures.
Exclusion Criteria:
1. Patients who have received prior systemic therapies for MM other than initial
IMiD/PI/anti-CD38-based combination therapy (receiving limited cycles of other
induction therapies, eg, cyclophosphamide, bortezomib and dexamethasone (CyBorD) or
pulse dexamethasone prior to main induction is allowed). Exclusions include high-dose
melphalan with autologous stem cell transplant (HDM-ASCT) and allogeneic stem cell
transplant (SCT).
Note: Continuous systemic corticosteroid treatment with more than 10 mg per day of
prednisone or anti-inflammatory equivalent within 72 hours of start of study drug is
not permitted.
2. Patients who are receiving any other investigational agents for any reasons.
3. Patients who receive a live attenuated vaccine within 4 weeks of scheduled study
treatment administration.
4. Contraindication to any concomitant medication, including those medications
administered for infusion reaction, antiviral, antibacterial, anticoagulation, tumor
lysis, or hydration prophylaxis given prior to therapy (Sections 4.8, 4.9, and 7).
5. Patient has any of the following:
1. Human immunodeficiency virus (HIV)-positive with 1 or more of the following:
History of acquired immune deficiency syndrome (AIDS)-defining conditions
cluster of differentiation 4 (CD4) count <350 cells/mm3.
Detectable viral load during screening or within 6 months prior to
screening.
Not receiving highly active anti-retroviral therapy.
Had a change in anti-retroviral therapy within 6 months of the start of
screening.
Receiving anti-retroviral therapy that may interfere with study treatment
as assessed after discussion with the Sponsor-Investigator in consultation
with study pharmacist. 2. Hepatitis B infection (ie, hepatitis B surface antigen (HBsAg) or hepatitis B
virus (HBV)-deoxyribonucleic acid [DNA] positive). Patients with resolved
infection (ie, patients who are HBsAg negative but positive for antibodies to
hepatitis B core antigen (anti-HBc) and/or antibodies to hepatitis B surface
antigen (anti-HBs)) must be screened using real-time polymerase chain reaction
(PCR) measurement of HBV DNA levels. Those who are PCR positive will be excluded.
In the event the infection status is unclear, quantitative viral levels are
necessary to determine the infection status. EXCEPTION: Patients with serologic
findings suggestive of HBV vaccination (anti-HBs 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. Active hepatitis C infection as measured by positive hepatitis C virus
(HCV)-ribonucleic acid (RNA) testing. Participants with a history of HCV antibody
positivity must undergo HCV-RNA testing. If a participant with history of chronic
hepatitis C infection (defined as both HCV antibody and HCV RNA positive)
completed antiviral therapy and has undetectable HCV-RNA 12 weeks following the
completion of therapy, the participant is eligible for the study.
6. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to the experimental agents used in study.
7. Female patient refuses to discontinue breastfeeding her infant during study treatment
or within 6 months after receiving the last dose of study treatment (Section 4.11).
8. Women of childbearing potential (WOCBP) and men who are unwilling to practice highly
effective contraception prior to the initial dose/start of the first treatment, during
the study, and for at least 6 months after the last dose.
- - Highly effective contraceptive measures for women include: stable use of combined
(estrogen and progestogen containing) hormonal contraception (oral, intravaginal,
transdermal) or progestogen-only hormonal contraception (oral, injectable,
implantable) associated with inhibition of ovulation initiated 2 or more
menstrual cycles prior to screening intrauterine device (IUD); intrauterine
hormone-releasing system (IUS) bilateral tubal ligation vasectomized partner
(provided that the male vasectomized partner is the sole sexual partner of the
study participant and that the partner has obtained medical assessment of
surgical success for the procedure) and/or sexual abstinence.
- - WOCBP are defined as women who are fertile following menarche until becoming
post-menopausal, unless permanently sterile.
Permanent sterilization methods
include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A
post-menopausal state is defined as no menses for 12 months without an
alternative medical cause. A high follicle stimulating hormone (FSH) level in the
postmenopausal range may be used to confirm a post-menopausal state in women not
using hormonal contraception or hormonal replacement therapy. However, in the
absence of 12 months of amenorrhea, a single FSH measurement is insufficient to
determine the occurrence of a post-menopausal state.
- - Male study participants with WOCBP partners are required to use condoms unless
they are vasectomized or practice sexual abstinence.
Male study participants
should not donate sperm during the study, and for at least 6 months after the
last dose. Vasectomized partner or vasectomized study participant must have
received medical assessment of the surgical success.
- - Sexual abstinence is considered a highly effective method only if defined as
refraining from heterosexual intercourse during the entire period of risk
associated with the study treatments.
The reliability of sexual abstinence needs
to be evaluated in relation to the duration of the clinical trial and the
preferred and usual lifestyle of the patient.
Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods),
withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method
(LAM) are not acceptable methods of contraception. Female condom and male condom
should not be used together (Section 4.11).
9. Presence of the following cardiac conditions:
New York Heart Association stage III or IV congestive heart failure.
Myocardial infarction or coronary artery bypass graft ≤ 6 months prior to
study enrollment.
History of clinically significant ventricular arrhythmia or unexplained
syncope, not believed to be vasovagal in nature or due to dehydration.
Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG)
abnormalities.
Unstable or uncontrolled disease/condition related to or affecting cardiac
function (eg, unstable angina)
10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, venous thromboembolic disease, hemorrhage, pulmonary fibrosis, pneumonitis,
neurological condition, active autoimmune disease or a documented history of
autoimmune disease with the exception of vitiligo, type I diabetes, and prior
autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and
laboratory testing, or psychiatric illness/social situations within 2 weeks that would
limit compliance with study requirements.
11. Active malignancy other than MM requiring treatment in the past 12 months.
Malignancies treated within the past 12 months that are considered cured with minimal
risk of recurrence are allowed.
12. Have any condition that, in the opinion of the Investigator, would compromise the
well-being of the patient or the study or prevent the patient from meeting or
performing study requirements.
13. Patients with impaired decision-making capacity will not be enrolled on this trial.
