A Study to Evaluate the Effectiveness and Safety of bb2121 in Subjects with Relapsed and Refractory Multiple Myeloma and in Subjects with Clinical High-Risk Multiple Myeloma

Overview

About this study

The purpose of this study is to determine the effectiveness and safety of bb2121 in subjects with relapsed and refractory MM (Cohort 1) and in subjects with HR MM having progressed within one year of initial treatment (Cohort 2). Approximately 122 subjects will be enrolled into one of two cohorts. Cohort 1 will enroll approximately 73 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens. Cohort 2 will enroll approximately 49 MM subjects with 1 prior anti-myeloma treatment regimen and HR disease defined as Stage III by the Revised International Staging System (R-ISS) and early relapse. The cohorts will start in parallel and independently.

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. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
  • Subject has measurable disease, defined as:
    • M-protein (serum protein electrophoresis [sPEP] or urine protein electrophoresis [uPEP]): sPEP ≥0.5 g/dL or uPEP ≥200 mg/24 hours; and/or
    • Light chain MM without measurable disease in the serum or urine: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
  • Subjects with one of the following cohort specific requirements:
    • Cohort 1 RRMM subjects with ≥3 prior anti-myeloma treatment regimens:
      • Subject must have received at least 3 prior anti-myeloma treatment regimens'
        • Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen.
      • Subject must have undergone at least 2 consecutive cycles of treatment for each regimen, unless PD was the best response to the regimen;
      • Subject must have received prior treatment with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody;
      • Subject has evidence of PD on or within 60 days of the most recent prior treatment regimen;
      • Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen.
    • Cohort 2 subjects with 1 prior anti-myeloma treatment regimen:
      • Subject must have received only 1 prior anti-myeloma treatment regimen. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen;
      • Subject must have the following HR factors: R-ISS stage III
  • AND
  • Early relapse defined as:
    • Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must contain induction, ASCT (single or tandem) and LEN containing maintenance;
    • Cohort 2b: PD < 18 months since date of start of initial therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone;
    • Cohort 2c: Subject must have received minimum 3 cycles of induction therapy which must contain at minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone. Subjects must have had ASCT (single or tandem).
  • AND

    • < VGPR (excluding PD) at first assessment between 70 to 110 days after last ASCT, with initial therapy without consolidation and maintenance.

  • Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy.
  • Subject must have adequate vascular access for leukapheresis.
  • Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  • Subject is willing and able to adhere to the study visit schedule and other protocol requirements as well as agrees to continued follow up for up to 15 years as mandated by the regulatory guidelines for gene therapy trials.
  • Female subjects of childbearing potential (FCBP*) must:
    • Have a negative pregnancy test as verified by the Investigator, one negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test result at screening, prior to LD chemotherapy. This applies even if the subject practices true abstinence** from heterosexual contact;
    • 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 at least 1 year following last bb2121 infusion. Contraception methods must include 1 highly effective and 1 additional effective (barrier) method of contraception from screening until at least 12 months following bb2121 infusion and until CAR T cells are no longer present by qPCR on two consecutive tests;
    • Agree to abstain from breastfeeding during study participation and for at least 1 year post-bb2121 infusion and until CAR T cells are no longer present by qPCR on two consecutive tests.
      • *A female of childbearing potential (FCBP*) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
      • **True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Male subjects must:
    • Practice true abstinence** or agree to use a condom during sexual contact with a pregnant female or a female of childbearing for at least 1 year post bb2121 infusion, even if he has undergone a successful vasectomy from screening until at least 1 year following last bb2121 infusion and until CAR T cells are no longer present by qPCR on two consecutive tests.
    • Must not donate sperm for at least 12 months following last bb2121 infusion and until CAR T cells are no longer present by qPCR on two consecutive tests.
      • Note: Highly effective methods are defined as those that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. The following are examples of highly effective and additional effective methods of contraception:
        • Intrauterine device (IUD);
        • Hormonal (birth control pill, injections, implants);
        • Tubal ligation;
        • Partner's vasectomy;
        • Male condom (additional effective method);
        • Diaphragm (additional effective method);
        • Cervical cap (additional effective method.

* A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).

** True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

  • Subject used any investigational agents within 14 days of leukapheresis.
  • Subject received any of the following within the last 14 days of leukapheresis:
    • Plasmapheresis;
    • Major surgery (as defined by the investigator);
    • Radiation therapy other than local therapy for myeloma associated bone lesions;
    • Use of any systemic anti-myeloma drug therapy.
  • Subject with known central nervous system (CNS) involvement with myeloma.
  • Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation.
  • History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or other CNS bleed, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
  • Subject with active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically significant amyloidosis.
  • Subject has nonsecretory MM.
  • Subject has any of the following laboratory abnormalities:
    • Absolute neutrophil count (ANC) < 1,000/μL;
    • Platelet count < 50,000 mm3 in the absence of transfusion support (platelet transfusion within 7 days of screening);
    • Hemoglobin < 8 g/dL (< 4.9 mmol/L) (it is not permissible to transfuse a subject to reach this level);
    • Serum Creatinine Clearance (CrCl) < 45 mL/min;
    • Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L);
    • Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN);
    • Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert’s syndrome;
    • International ratio (INR) or partial thromboplastin time (PTT) > 1.5 × ULN, or history of Grade ≥ 2 hemorrhage within 30 days, or subject requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors).
  • Echocardiogram (ECHO) or multi-gated acquisition (MUGA) with left ventricular ejection fraction < 45%.
  • Subject with a history of Class III or IV congestive heart failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months prior to starting study treatment.
  • Inadequate pulmonary function defined as oxygen saturation (Sa02) < 92 % on room air.
  • Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine or systemic steroids at any dose). Intermittent topical, inhaled or intranasal corticosteroids are allowed.
  • Previous history of an allogeneic hematopoietic stem cell transplantation or treatment with any gene therapy-based therapeutic for cancer or investigational cellular therapy for cancer or BCMA targeted therapy.
  • Subject has received ASCT within 12 weeks prior to leukapheresis.
  • Subject has history of primary immunodeficiency.
  • Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B or active hepatitis A or C.
  • Subject has uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
  • Subject with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years with the exception of the following noninvasive malignancies:
    • Basal cell carcinoma of the skin;
    • Squamous cell carcinoma of the skin;
    • Carcinoma in situ of the cervix;
    • Carcinoma in situ of the breast;
    • Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
  • Subject is a female who is pregnant, nursing, or breastfeeding, or who intends to become pregnant during participation in the study.
  • Subject with known hypersensitivity to any component of bb2121 product, cyclophosphamide, fludarabine, and/or tocilizumab.
  • Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  • Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. This includes systemic fungal, bacterial, viral, or other infection that is uncontrolled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antimicrobial treatment) or requiring IV antimicrobials for management.
  • Subject has any condition that confounds the ability to interpret data from the study.

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

Peter Bergsagel, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20453738

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