Clinical Trials

Inclusion Criteria:

• Documented diagnosis of relapsed/refractory multiple myeloma as defined by the IMWG consensus criteria for response and minimal residual disease assessment in multiple myeloma (Kumar et al, 2016):
  • Relapsed and refractory multiple myeloma is a disease that has not attained at least partial response while on salvage therapy or that has progressed within 60 days of last therapy.
• Subjects must have measurable disease including at least one of the following criteria:
  • Serum M-protein ≥ 0.5 g/dL;
  • Urine M-protein ≥ 200 mg/24 hours;
  • Involved serum free light chain (FLC) level ≥ 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal.
• Subjects must have received ≥ 3 prior MM lines of therapy:
  • Induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single line;
  • Received prior proteasome inhibitor, immunomodulatory agent, and an anti-CD38 antibody (unless contraindicated) as monotherapy or in combination, with at least 2 consecutive cycles of each line unless progressive disease was the best response to the line;
  • Refractory to the last treatment line;
  • Previous exposure to an anti-BCMA antibody-based therapy (e.g., bispecific, conjugated, or other) is permitted. (Previous CAR T therapy is not permitted). Subjects must have had an objective response of PR or better for at least 3 months to the previous anti-BCMA therapy. Subjects who experienced Grade ≥3 CRS or neurotoxicity related to their anti-BCMA therapy are excluded.
• Male or female subjects age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Absence of donor (product)-specific anti-HLA antibodies.
• Adequate hematologic function (if these values are not maintained just before lymphodepletion, discuss with sponsor), including:
  • Absolute neutrophil count (ANC) ≥ 1,000/mm^3 in the absence of growth factor support (G-CSF within 7 days or peg-G-CSF within 14 days);
  • Platelet count ≥ 50,000/mm^3 in the absence of transfusion support (platelet transfusion within 7 days);
  • Hemoglobin ≥ 8 g/dL in the absence of transfusion support (RBC or whole blood within 7 days).
• Adequate renal function, including:
  • Estimated creatinine clearance (Cockcroft-Gault) or estimated glomerular filtration rate (GFR) (MDRD) ≥ 60 mL/min or directly measured with a 24-hour urine collection test.
• Adequate liver function, including:
  • Total bilirubin ≤ 1.5 x ULN except in subjects with Gilbert’s Syndrome who must have a total bilirubin ≤ 3 x ULN;
  • Aspartate and alanine aminotransferase (AST and ALT) ≤ 3 x ULN; ≥ 5.0 x ULN if there is liver involvement by the tumor;
  • Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN in case of bone metastasis).
• Normal blood oxygen saturation levels (SpO2) ≥ 91% on room air.
• Left ventricular ejection fraction (LVEF) ≥ 50% and no clinically significant pericardial or pleural effusion at screening.
• Life expectancy of at least 3 months without treatment.
• Resolved acute effects of any prior therapy to baseline severity or National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 Grade ≤ 1 except for adverse events (AEs) not constituting a safety risk by investigator judgment.
• If a subject experiences any Grade ≥ 2 AE, or any SAE, after signing informed consent and before starting lymphodepletion, the event(s) and the decision whether or not to proceed with study treatment must be discussed with the Sponsor before initiating lymphodepletion.
• Seronegative for hepatitis B surface antigen. If hepatitis B surface antigen is positive, the subject must be tested by RT-PCR and be HBV DNA negative. If positive, hepatitis B tests can be further evaluated by confirmatory tests, and if viral load is negative, the subject can be enrolled.
• Seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then subjects must be tested by RT-PCR and be HCV RNA negative.
• Serum pregnancy test (for females of childbearing potential) negative at screening.
• Female subjects of nonchildbearing potential must meet at least 1 of the following criteria:
  • Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormone level confirming the postmenopausal state;
  • Have undergone a documented hysterectomy and/or bilateral oophorectomy;
  • Have medically confirmed ovarian failure. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.

Exclusion Criteria:

• Subjects with known active or history of central nervous system (CNS) or leptomeningeal involvement of myeloma or plasma cell leukemia.
• Clinically significant CNS dysfunction; e.g., seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement.
• Current or history of thyroid disorder (including hyperthyroidism), except for subjects with hypothyroidism controlled on a stable dose of hormone replacement therapy.
• Any other active malignancies that required systemic treatment within 3 years prior to start of lymphodepletion (e.g., cancers that can be adequately treated with local measures like surgical resection or local radiation with limited chance of recurrence or spread such as basal cell or squamous cell skin cancer, carcinoma in situ, or low Gleason score prostate cancers are acceptable).
• Major surgery within 3 months prior to the start of lymphodepletion.
• Radiation therapy within 2 weeks prior to the start of lymphodepletion.
• Autologous stem cell transplantation within last 6 weeks prior to the start of lymphodepletion.
• Any prior allogeneic hematopoietic stem cell transplantation.
• Systemic anti-cancer therapy within 2 weeks prior to the start of lymphodepletion.
• Any exposure to rituximab or rituximab biosimilar within the past 2 years prior to the start of lymphodepletion.
• Participation in other studies involving investigational drug(s) within 28 days prior to lymphodepletion.
• Prior treatment with any gene therapy (including ALLO-715; other CAR T cell therapy is permitted).
• Prior treatment with anti-CD52 monoclonal antibody (ALLO-647 is permitted).
• On-going treatment with immunosuppressive agents:
  • Corticosteroid use within 1 week prior to first dose of ALLO-605 with the exception of inhaled steroid for asthma, topical steroid use, or another local corticosteroid administration;
  • Subjects requiring systemic steroids at daily doses ≥ 5 mg prednisone (or corticosteroid equivalent), or those who are administered steroids for myeloma control or WBC-count-lowering are not eligible for the study;
  • Infliximab must be stopped at least 45 days prior to administration of ALLO-605.
• Active and clinically significant autoimmune disease within the last 2 years including, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel disease, immune cytopenias, severe psoriasis, autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.
• Subject known to be refractory to platelet or red blood cell transfusions.
• Subjects with active uncontrolled bacterial, fungal, or viral infection, including known HIV infection or acquired immunodeficiency syndrome-related illness, not controlled by adequate treatment, at screening, and presence of positive blood cultures within 7 days before ALLO-605 infusion.
• Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted.
• Any form of primary or acquired immunodeficiency (e.g., severe combined immunodeficiency disease).
• Any of the following in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsade de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), left anterior hemiblock (bi-fascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF, New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other clinical significant episode of thrombo-embolic disease. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥ 2, or atrial fibrillation of any grade (or Grade ≥ 2 if asymptomatic). Subjects with cardiac amyloidosis are not eligible.
• History of hypertension crisis or hypertensive encephalopathy within 6 months prior to screening.
• Known or suspected hypersensitivity to murine or bovine products.
• Fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for at least 12 months after ALLO-605 infusion.
• Other acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
• Subjects unwilling to participate in an extended safety monitoring period.

Eligibility last updated 9/21/21. Questions regarding updates should be directed to the study team contact.