Overview

This is a phase II study where patients will undergo isatuximab and lenalidomide maintenance if they are MRD-positive after Autologous Stem Cell Transplant (ASCT)

Eligibility

NOTE: Females are considered of childbearing potential unless they are surgically sterile

        (have undergone a hysterectomy or bilateral oophorectomy) or they are naturally
        postmenopausal for at least 12 consecutive months.
        12. Patients must be willing to take appropriate DVT prophylaxis, either aspirin, low
        molecular weight heparin, direct oral anticoagulants, or warfarin while receiving
        lenalidomide.
        Inclusion Criteria:
          1. Age > 18 years
          2. Patients must have a confirmed diagnosis of multiple myeloma according to IMWG
             criteria. Patients with smoldering multiple myeloma, or plasma cell leukemia are not
             eligible. Patients must not have significant amyloid organ dysfunction per the study
             chair.
          3. R-ISS stage 1, 2 or 3 at diagnosis. If stage at diagnosis is not known, patient may be
             enrolled if the intent is to treat with post -ASCT maintenance therapy.
          4. Received up to or less than 2 lines of therapy prior to ASCT (as long as they did not
             meet IMWG refractory disease for CD38 monoclonal antibody or lenalidomide therapies as
             defined in exclusion).
          5. Patients are planned to undergo ASCT with high dose melphalan, or have completed ASCT
             with high dose melphalan within the last 180 days and have not yet initiated post-ASCT
             maintenance.
          6. Obtain at least partial response according to IMWG criteria after induction therapy
             and ASCT
          7. ECOG performance status of 0, 1, or 2 within 30 days prior to enrollment.
          8. Demonstrate adequate organ function as defined in the table below; all screening labs
             are to be obtained within 30 days prior enrollment.
             Hematologic White blood cell (WBC) ≥ 1500/mm3 Absolute Neutrophil Count (ANC) ≥
             1000/mm3 Platelets ≥ 50,000/mm3 Renal Calculated creatinine clearance ≥ 30 mL/min
             using either the Cockcroft-Gault formula or estimated GFR, and not requiring
             continuous or intermittent dialysis Hepatic Bilirubin ≤ 2.5 × upper limit of normal
             (ULN) Aspartate aminotransferase (AST) ≤ 2.5 × ULN Alanine aminotransferase (ALT) ≤
             2.5 × ULN Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)
             Activated Partial Thromboplastin Time (aPTT)1 ≤ 2 × ULN Note: Patients on
             anticoagulation are exempt from meeting this criterion
          9. Standard of care lenalidomide will not be provided by the sponsor or study and
             therefore study subjects must have confirmed access to lenalidomide for use during the
             study at the time of enrollment.
         10. Must be able to take and swallow oral medication (capsules) whole. Patients may not
             have any known impairment of gastrointestinal function or gastrointestinal disease
             that may significantly alter the absorption of study drug (e.g. ulcerative disease,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
             resection).
         11. Females of childbearing potential and males must be willing to abstain from
             heterosexual activity or to use 2 forms of effective methods of contraception from the
             time of informed consent until 5 months for females, and 1 month for males after
             treatment discontinuation. The two contraception methods can be comprised of two
             barrier methods, or a barrier method plus a hormonal method. Interventions such as
             IUD, tubal ligation, hormonal (birth control pills, injections, hormonal patches,
             vaginal rings, or implants), or partner's vasectomy, all count as one method. For
             women of childbearing potential (WOCBP), a second form must also be used. Men must
             agree to use a latex condom during sexual activity with a female of childbearing
             potential, irrespective of a prior vasectomy, during the study treatment and for 1
             month after the end of treatment. Females of childbearing potential agree to not plan
             a pregnancy for 1 month after the last dose of study medication. Females of
             childbearing potential must agree to ongoing pregnancy testing during the treatment
             period.
             NOTE: Females are considered of childbearing potential unless they are surgically
             sterile (have undergone a hysterectomy or bilateral oophorectomy) or they are
             naturally postmenopausal for at least 12 consecutive months.
         12. Patients must be willing to take appropriate DVT prophylaxis, either aspirin, low
             molecular weight heparin, direct oral anticoagulants, or warfarin while receiving
             lenalidomide.
        Exclusion Criteria:
          1. Refractory to anti-CD38 monoclonal antibody therapy OR lenalidomide as defined by the
             IMWG (defined as non-responsive or progressive disease on therapy or within 60 days of
             last treatment).
          2. MRD negative CR (at a resolution of 10-5) at screening.
          3. Prior intolerance to isatuximab or lenalidomide.
          4. Prior allogeneic stem cell transplant.
          5. Prior solid organ transplant requiring immunosuppressive therapy.
          6. Known additional malignancy that is active and/or progressive requiring treatment;
             exceptions include adequately treated basal cell or squamous cell skin cancer, in situ
             cervical cancer, adequately treated Stage I or II cancer from which the patient is
             currently in complete remission, or any other cancer from which the patient has been
             disease free for three years.
          7. Known CNS involvement by multiple myeloma, defined by positive CSF cytology for plasma
             cells, leptomeningeal involvement, or parenchymal CNS plasmacytoma at time of
             enrollment. Lumbar puncture is not required.
          8. Treatment with any investigational drug within 30 days prior to enrollment.
          9. Planned transplant is considered part of tandem autologous transplant approach for
             newly diagnosed MM.
         10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris or coronary
             angioplasty, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI Common
             Terminology Criteria for Adverse Events [CTCAE] v5.0 Grade ≥ 2), intracardiac
             defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (≥
             Grade 3), or known psychiatric illness/social situations that would limit compliance
             with study requirements.
         11. Pregnant women are excluded from this study because lenalidomide is an agent with the
             potential for teratogenic or abortifacient effects. Because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with lenalidomide, breastfeeding should be discontinued if the mother is
             treated with lenalidomide.
         12. Patients with known history of testing positive for human immunodeficiency virus (HIV)
             or known acquired immunodeficiency syndrome (AIDS) may be enrolled if the viral load
             by polymerase chain reaction (PCR) is undetectable with active treatment and absolute
             lymphocyte count ≥ 350/ul. Antiviral therapy for HIV should continue throughout the
             study.
         13. Patients with a positive test for hepatitis B virus surface antigen (HBsAg) and/or HBV
             DNA indicating uncontrolled or active HBV infection. Patients with negative HBsAg and
             positive HBV viral load can be evaluated by a specialist for start of anti-viral
             therapy and study treatment can be proposed if HBV viral load becomes negative and
             other study criteria are met. Participants can be eligible if anti-HBc IgG is
             positive, but HBsAg and HBV viral load is negative (i.e., cleared infection).
         14. Patients with known hepatitis C virus (HCV) viral load indicating acute or chronic
             infection might be enrolled if the viral load by PCR is undetectable with/without
             active treatment. If a patient was started on antiviral therapy prior to study
             enrollment, antiviral therapy should continue throughout the study.
        NOTE: HIV, Hep B, and Hep C viral testing is not required and this criterion apply only to
        patients with a known history of HCV infection.