Clinical Trials

Inclusion Criteria: 

• ≥ 18 years of age.
• Documented diagnosis of multiple myeloma according to IMWG diagnostic criteria.
• Measurable disease at Screening as defined by any of the following:
  • Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dL or urine M-protein level ≥ 200 mg/24 hours; or
  • Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
    • Note: Local laboratory assessments may be used to establish measurable disease at Screening, with local laboratory result ≥ 125% of requirements.
• Received at least 3 prior multiple myeloma treatment lines of therapy or are double refractory to an IMiD and PI (refractory multiple myeloma as defined by IMWG consensus criteria 29).
  • Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single line of therapy.
    • Undergone at least 1 complete cycle of treatment for each line of therapy, unless PD was the best response to the line of therapy.
• Received as part of previous therapy a PI, an IMiD, and an anti-CD38 antibody (prior exposure can be from different monotherapy or combination lines of therapy).
• Subject must have documented evidence of progressive disease based on investigator’s determination of response by the IMWG criteria on or within 12 months of their last line of therapy.  Confirmation may be from either central or local testing. Also, subjects with documented evidence of progressive disease (as above) within the previous 6 months and who are refractory or non-responsive to their most recent line of therapy afterwards are eligible.
• ECOG Performance Status grade of 0 or 1.
• Clinical laboratory values meeting the following criteria during the Screening Phase:
• HEMOTOLOGY
  • Hemoglobin
    • ≥ 8.0 g/dL (≥ 5 mmol/L) (without prior red blood cell [RBC] transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted).*
  • Platelets
    • ≥ 50 x 10^9/L (must be without transfusion support in the 7 days prior to the laboratory test)
  • Lymphocyte count
    • ≥ 0.3 x 10^9/L
  • Absolute Neutrophil Count (ANC)
    • 0.75×10^9/L (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test)
• CHEMISTRY
  • AST and ALT
    • ≤ 3.0 × upper limit of normal (ULN)
  • Creatinine clearance
    • ≥ 40 mL/min/1.73 m^2 based upon Modified Diet in Renal Disease formula calculation or a 24-hour urine collection.
  • Total bilirubin
    • ≤ 2.0 × ULN; except in subjects with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤.5 × ULN is required)
  • Corrected serum calcium
    • ≤ 12.5 mg/dL (≤3.1 mmol/L) or free ionized calcium ≤ 6.5 mg/dl (≤1.6 mmol/L)

* For subjects who meet the inclusion criteria at screening, transfusion of RBCs is permitted after screening as needed to maintain a hemoglobin level ≥ 8.0 g/dL.

• Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of cyclophosphamide and fludarabine using a highly sensitive serum pregnancy test (β human chorionic gonadotropin [β-hCG]).
• When a woman is of childbearing potential the following are required:
  • Subject must agree to practice a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) and agree to remain on a highly effective method of contraception from the time of signing the informed consent form (ICF) until 1 year after receiving a JNJ-68284528 infusion. Examples of highly effective contraceptives include
    • user-independent methods:
      • implantable progestogen-only hormone contraception associated with inhibition of ovulation; 
      • intrauterine device;
      • intrauterine hormone-releasing system;
      • vasectomized partner.
    • user-dependent methods:
      • combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral or intravaginal or transdermal;
      • progestogen-only hormone contraception associated with inhibition of ovulation (oral or injectable).
• In addition to the highly effective method of contraception a man:
  • Who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (e.g., condom with spermicidal foam/gel/film/cream/suppository) from the time of signing the ICF until 1 year after receiving a JNJ-68284528 infusion;
  • +Who is sexually active with a woman who is pregnant must use a condom.
• Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, during the study and for 1 year after the last dose of study treatment.
  • Note: Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the efficacy of the contraceptive method.
• Subject must sign an ICF indicating that he or she understands the purpose of procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard of-care for the subject’s disease.
• Willing and able to adhere to the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

• Prior treatment with CAR-T therapy directed at any target.
• Any therapy that is targeted to BCMA.
• Diagnosed or treated for invasive malignancy other than multiple myeloma, except:
  • Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before enrollment; or
  • Adequately treated non-melanoma skin cancer without evidence of disease.
• Prior antitumor therapy as follows, prior to apheresis:
  • Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least 5 halflives, whichever is less;
  • Monoclonal antibody treatment for multiple myeloma within 21 days;
  • Cytotoxic therapy within 14 days;
  • Proteasome inhibitor therapy within 14 days;
  • Immunomodulatory agent therapy within 7 days;
  • Radiotherapy within 14 days. However, if the radiation portal covered ≤ 5% of the bone marrow reserve, the subject is eligible irrespective of the end date of radiotherapy.
• Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.
• The following cardiac conditions:
  • New York Heart Association (NYHA) stage III or IV congestive heart failure
  • Myocardial infarction or coronary artery bypass graft (CABG) ≤ 6 months prior to enrollment
  • History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
  • History of severe non-ischemic cardiomyopathy
  • Impaired cardiac function (LVEF < 45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed ≤ 8 weeks of apheresis).
• Received a cumulative dose of corticosteroids equivalent to ≥ 70 mg of prednisone within the 7 days prior to apheresis
• Received either of the following:
  • An allogenic stem cell transplant within 6 months before apheresis. Subjects who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD).
  • An autologous stem cell transplant ≤ 12 weeks before apheresis.
• Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma.
• Stroke or seizure within 6 months of signing ICF.
• Plasma cell leukemia at the time of screening (> 2.0 x 10^9/L plasma cells by standard differential), Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary AL amyloidosis.
• Seropositive for human immunodeficiency virus (HIV).
• Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis.
• Hepatitis B infection. In the event the infection status is unclear, quantitative levels are necessary to determine the infection status.
• Hepatitis C infection defined as (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA positive) or known to have a history of hepatitis C. For subjects with known history of HCV infection, confirmation of sustained virologic response [SVR] is required for study eligibility, defined as ≥24 weeks after completion of antiviral therapy.
• Supplemental oxygen use to maintain adequate oxygenation.
• Known life threatening allergies, hypersensitivity, or intolerance to JNJ-68284528 or its excipients, including DMSO (refer to Investigator’s Brochure).
• Serious underlying medical condition, such as:
  • Evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection;
  • Active autoimmune disease or a history of autoimmune disease within 3 years;
  • Overt clinical evidence of dementia or altered mental status.
• Any issue that would impair the ability of the subject to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within 1 year after receiving study treatment.
• Plans to father a child while enrolled in this study or within 1 year after receiving study treatment.
• Major surgery within 2 weeks prior to apheresis, or has surgery planned during the study or within 2 weeks after study treatment administration.
  • Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.