| Eligibility |
Inclusion Criteria:
1. Signed informed consent form.
2. Patient is =18 years of age.
3. Patient is willing and able to adhere to the protocol requirements.
4. Patient with diagnosis of MM who has been treated with at least 2 prior lines of
treatment, including at least one cycle of high-dose chemotherapy with autologous
hematopoietic stem cell transplantation if the patient was eligible, and exposure to
an immunomodulatory imide drug (e.g. lenalidomide and/or pomalidomide), a proteasome
inhibitor, and an anti-CD38 antibody.
(Note: Induction therapy, up to 2 cycles of high-dose chemotherapy with autologous
hematopoietic stem cell transplantation, and subsequent consolidation and/or
maintenance therapy are considered one line of treatment).
5. At least one of the following subcriteria must be measured in the patient:
- Serum M-protein greater or equal to 0.5 g/dL
- Urine M-protein greater or equal to 200 mg/24 h
- Serum free light chain (FLC) assay: involved FLC level greater or equal to 10
mg/dL (100 mg/L) provided serum FLC ratio is abnormal
- A biopsy-proven evaluable plasmacytoma
- Bone marrow plasma cells >10% of total bone marrow cells (>30% if bone marrow
plasma cells are the only marker of measurable disease)
6. Patients previously treated with an anti-SLAMF7 antibody are eligible.
7. Karnofsky performance status =60%. If patient has a Karnofsky performance status <60%
(e.g. after a spinal cord injury) but is judged to be medically fit by the
investigator, patient is eligible.
8. Female patients of childbearing potential must:
1. have a negative pregnancy test (blood) at screening.
2. either commit to true abstinence from heterosexual contact or agree to use, and
be able to comply with, effective measures of contraception without interruption,
from screening through 1 year following the investigantional medicinal product
(IMP) infusion. A highly effective method of contraception or birth control
(failure rate less than 1% per year when used consistently and correctly) must be
practiced. The patient should be informed of the potential risks associated with
becoming pregnant while enrolled in this clinical trial. Reliable methods for
this trial are: combined (estrogen and progestogen containing) hormonal
contraception associated with inhibition of ovulation (oral, intravaginal,
transdermal), progestogen-only hormonal contraception associated with inhibition
of ovulation (oral, injectable, implantable), intrauterine device, intrauterine
hormone-releasing system, bilateral tubal occlusion, sexual abstinence or
vasectomized sexual partner. Abstinence is only accepted as true abstinence: 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.) Postmenopausal (no
menses for at least 1 year without alternative medical cause) or surgically
sterile female patients (tubal ligation, hysterectomy or bilateral oophorectomy)
may be enrolled.
3. Agree to abstain from breast feeding during the study participation and for 1
year after the IMP infusion.
9. Male patients must practice true abstinence or agree to use a condom during sexual
contact with a pregnant female or a female of childbearing potential for at least 1
year after IMP infusion, even if he has undergone a successful vasectomy.
Exclusion Criteria:
1. Patient has undergone a prior allogeneic stem cell transplant with either standard or
reduced intensity conditioning =12 months prior to leukapheresis.
2. Patient has undergone a prior allogeneic stem cell transplant with either standard or
reduced intensity conditioning >12 months, and suffers on chronic Graft-versus-Host
Disease and/or is on systemic immune-suppressants.
3. Patient with diagnosis of MM
1. in first relapse following an autologous stem cell transplantation or
2. in second relapse that subsequently achieves a complete response that is
considered being a candidate for an allogeneic stem cell transplantation, unless
the patient explicitly denies undergoing an allogeneic stem cell transplantation.
4. Patient has received anti-CD38 and/or anti-SLAMF7 antibodies =8 weeks prior to
leukapheresis.
5. Ongoing treatment with systemic immune-suppressants (e.g. systemic cyclosporine or
systemic steroids at any dose).
(Note: Physiologic steroid replacement therapy, topical immune-suppressants as e.g.
cyclosporine/tacrolimus eye drops and topical steroids are permitted.)
6. Echocardiogram with left ventricular ejection fraction <45%.
7. Inadequate renal function defined by creatinine clearance (CrCl) =45 mL/min using
Cockcroft-Gault equation.
8. Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine
aminotransferase (ALT) >2.5 x upper limit of normal (ULN) and total bilirubin >1.5 x
ULN (unless due to Gilbert's syndrome and direct bilirubin is =1.5 x ULN; unless due
to intrahepatic myeloma lesions as demonstrated by MRI or positron emission tomography
(PET)/computed tomography (CT) not older than 4 weeks prior to screening).
9. International ratio (INR) or partial thromboplastin time (PTT) >1.5 x ULN, unless on a
stable dose of anti-coagulant.
10. Evidence of human immunodeficiency virus (HIV) infection.
11. Seropositive for and with evidence of active viral infection with hepatitis B virus
(HBV), excluding
- Patients who are hepatitis B surface antigen negative and HBV viral DNA negative
- Patients who had hepatitis B but have received an antiviral treatment and show
non-detectable viral DNA for 6 months
- Patients who are seropositive because of hepatitis B virus vaccine
- Patients with known HBV infection but undetectable HBV viral load and on
anti-viral therapy to prevent HBV reactivation.
12. Seropositive for and with active viral infection with hepatitis C virus (HCV),
excluding
- Patients who had hepatitis C but had received an antiviral treatment and show no
detectable HCV viral RNA for 6 months.
13. Seropositive for syphilis on treponema pallidum hemagglutination test, excluding
- Patients with negative treponema pallidum antibody absorption test result
14. Patients with active infection (e.g. asymptomatic and symptomatic severe acute
respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) or other serious medical or
psychiatric disorder on investigators decision.
15. Pregnant or lactating women.
16. Current or previous (within 30 days of enrollment) treatment with another IMP.
17. Known abuse of alcohol, drugs, or medicinal products.
18. Employees of the sponsor, or employees or relatives of the investigator.
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