Open-label, Multi-center, Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Autologous CAR-BCMA T-cells (CT053) in Patients

Overview

About this study

The purpose of this study is to evaluate Chimeric Antigen Receptor T Cells targeting BCMA in patients with myeloma.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Please contact the study team to discuss whether or not you are eligible to participate in a study.

Inclusion Criteria:

  • Patients must have voluntarily signed ICF.
  • Patients must be ≥ 18 and ≤ 80 years old.
  • The patients have received at least 3 prior lines of therapy for MM, or in the presence of high-risk cytogenetics (del[17p], t[4;14], t[14;16] or gain[1q]) should have had at least 2 prior lines of therapy. Induction therapy followed by autologous transplantation and maintenance therapy represents one line of therapy; lines of therapy are defined per International Myeloma Workshop Consensus Panel (Rajkumar et al, 2011). For each line of therapy, the patient should have received at least one complete treatment cycle (2016 IMWG).
  • The patients should have received treatment with at least one proteasome inhibitor, one IMiD and daratumumab.
    • Note: Patients should be either relapsed or refractory to daratumumab or can’t tolerate the treatment of daratumumab.
  • The patient should be refractory to the last line of therapy (progression on or within 60 days of discontinuing treatment).
  • The patients should have measurable disease based on at least one of the following parameters:
    • Serum M-protein ≥ 0.5 g/dL;
    • Urine M-protein ≥ 200 mg/24 hrs;
    • Serum free light chain (FLC): involved FLC level ≥ 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal.
  • Estimated life expectancy > 12 weeks.
  • ECOG performance score 0-1.
  • Patients should meet the following:
    • Complete blood count (CBC) results (without transfusion and growth factor support) within 7 days of testing:
      • ANC ≥ 1.0 × 10^9 /L, platelet count ≥ 75 × 10^9/L (If the proportion of plasma cells in the bone marrow is > 50%, patients with platelet ≥ 50 × 10^9 /L will be eligible), Hb ≥ 7.0 g/dL;
        • Note: Platelet count ≥ 50 × 10^9/L will be eligible for leukapheresis after medical monitor’s approval.
    • Blood biochemistry:
      • Creatinine clearance ≥ 45 mL/min (Cockcroft –Gault formula), alanine aminotransferase (ALT) ≤ 2.5 × upper limit normal (ULN), aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin ≤ 2 × ULN (except patients with Gilbert’s syndrome who must have a total bilirubin ≤ 3 × ULN).
    • Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis.
    • Women of childbearing age must undergo a serum pregnancy test with negative results before screening, and are willing to use effective and reliable method of contraception for at least 6 months after T cell infusion.
    • Men must be willing to use effective and reliable method of contraception for at least 6 months after T cell infusion.

Exclusion Criteria:

  • Pregnant or lactating women.
  • Patients with HIV, active hepatitis C virus (HCV), or active hepatitis B virus (HBV) infection. History of treated hepatitis B or C is permitted if the viral load is undetectable per qPCR and or nucleic acid testing.
  • Patients with any uncontrolled active infection.
  • Patients with AEs from previous treatment that have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 ≤ 1, excluding hair loss, neuropathy and other events that the treating physician can determine are unlikely to lead to cumulative toxicity from lymphodepletion.
  • Patients who have had either:
    • Previous anti-BCMA therapy (antibody drug conjugate or bi-specific T cell engager) without response to treatment (≥ PR);
    • Previous anti-BCMA CAR-T therapy (with or without response to the treatment).
  • Patients who have active acute graft versus host disease (GvHD) or chronic GvHD, or patients who had previous Grade 2 or higher GvHD.
  • Patients have received stem cell transplantation less than 12 weeks before leukapheresis.
  • Patients have received any anti-cancer treatment 2 weeks before leukapheresis or 3 weeks before lymphodepletion. If the field of radiation covers ≤ 5% of the bone marrow, the subjects are eligible to participate in the study regardless of the radiotherapy end date; Note: Any treatment encroaching into the 14- or 21-day washout period listed under items 8 and 9 may be allowable if discussed with and approved by the study medical monitor.
  • Patients have received ≥ 20 mg prednisone daily or other equivalent dose of steroids within 14 days before leukapheresis or lymphodepletion.
  • Patients have plasma cell leukemia, Waldenström macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome or clinically significant symptomatic immunoglobulin light chain (AL) amyloidosis with evidence of end-organ damage.
  • Patients have been administered live attenuated vaccine 4 weeks before leukapheresis or lymphodepletion.
  • Patients allergic to Flu, Cy, tocilizumab, dimethyl sulfoxide (DMSO) or CT053 CAR-BCMA T cell.
  • Patients have any of the following cardiac conditions:
    • New York Heart Association (NYHA) stage III or IV congestive heart failure;
    • Myocardial infarction or coronary artery bypass graft 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;
    • Uncontrolled blood pressure as defined as systolic > 160 mmHg, diastolic > 100 mmHg;
    • Left ventricular ejection fraction (LVEF) < 45% as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan; or
    • Other conditions that researchers believe that participating in this clinical trial may endanger the health of the patients.
  • Patients have one of the following pulmonary conditions: a) forced expiratory volume in 1 second (FEV1) < 60%, b) patients have active obstructive chronic pulmonary disease, c) patients are oxygen dependent as defined by the blood oxygen saturation can only be maintained > 92% by oxygen inhalation (finger oxygen detection method).
  • Patients are known to have active autoimmune diseases including but not limited to psoriasis, rheumatoid arthritis and other needs of long-term immunosuppressive therapy.
  • Patients with second malignancies in addition to MM are not eligible if the second malignancy has required treatment within the past 3 years or is not in complete remission. There are two exceptions to this criterion: successfully treated non-metastatic basal cell or squamous cell skin carcinoma.
  • Patients have central nervous system (CNS) metastases or CNS involvement (including cranial neuropathies or mass lesions and leptomeningeal disease). Patients with history of spinal cord compression from MM are eligible provided spinal cord compression has been treated with surgery or radiation at least 28 days prior to study entry.
  • Patients have significant neurologic disorders such as seizures or dementia or prior brain bleeding (subarachnoid or subdural hematoma within the past 5 years) and unable to safely stop anticoagulation treatment during the screening and treatment phase.
  • Patients are unable or unwilling to comply with the requirements of clinical trial.
  • Patients have received major surgery 1 weeks prior to leukapheresis or 3 weeks prior to lymphodepletion (excluding cataract and other local anesthesia).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Jeremy Larsen, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

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Rochester, Minn.

Mayo Clinic principal investigator

Shaji Kumar, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Shaji Kumar, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20472611

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