Blinatumomab Expanded T-cells (BET) in Indolent Non-Hodgkin Lymphomas/Chronic Lymphocytic Leukemia (BET2017)

This is an interventional treatment trial for Indolent Non-Hodgkin Lymphomas/Chronic Lymphocytic Leukemia Read More

Inclusion Criteria:

• 1. Male or female patients 18 years or older 2. Confirmed diagnosis of the following CD20+ iNHL or CLL according to (World Health Organization ) WHO criteria:

  • Follicular NHL
  • Marginal zone NHL (splenic, extranodal or nodal)
  • Lymphocytic lymphoma/CLL without del(17p) or TP53 mutations 3. No previous chemotherapy. Previous radiotherapy for localized disease is admitted 4. Requirement for treatment:
  • For CLL, active disease is defined as meeting at least one of the International Workshop on CLL guidelines (Hallek et al., 2008)
  • For iNHL, active disease is defined as meeting at least one of the Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria (Brice et al., 1997) 5. Indication to treatment with either fludarabine, cyclophosphamide and rituximab or bendamustine and rituximab 6. Presence of peripheral blood clone ≥10% of total lymphocytes (with absolute lymphocyte count >800 x106/L) at study entrance 7. Written informed consent prior to any study procedures being performed

Additional inclusion criteria to be met at study entry (i.e. before BET infusion):

8. Achieving at least a partial response after three chemo-immunotherapy cycles 9. Absence of any serious therapy-related complications that might affect interpretation of the results of the study or render the subject at high risk from treatment complications 10. Production of adequate BET numbers (counted on CD3+ cells: ≥0.5 x 109) 11. For female patients:

1. being postmenopausal for at least 1 year before the screening visit, OR
2. being surgically sterile, OR
3. if they are of childbearing potential, must agree to practice highly effective method of contraception and one additional effective (barrier) method from the time of signing the informed consent until the end of study. Highly effective method of contraception includes: (i) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal; (ii) progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable (intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, sexual abstinence) OR
4. must agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject from the time of signing the informed consent until the end of study. [Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.]

For male patients, even if surgically sterilized (i.e., status postvasectomy):

1. with female partners of childbearing potential: must agree to practice barrier contraception (condom with or without spermicide) from the time of signing the informed consent until the end of study and his female partner must agree to practice method of contraception including one of the following: estrogen and progestogen containing hormonal contraception; inhibition of ovulation: oral, intravaginal, transdermal; progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable (intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion) from the time of signing the informed consent until the end of study.
2. must agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject from the time of signing the informed consent until the end of study. [Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.]
3. must agree to refrain from donating sperm

Exclusion Criteria:

1. ECOG (Eastern Cooperative Oncology Group) Performance Status >2
2. Active central nervous system (CNS) disease
3. Calculated creatinine clearance (by Cockroft-Gault) of < 50 ml/min or serum creatinine > 1.5x ULN (Upper Limit of Normal )
4. Concomitant or previous diagnosis of autoimmune hemolytic anemia or thrombocytopenia
5. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition requiring the sole hormone replacement are allowed to participate. Psoriasis requiring systemic treatment, or conditions expected to recur at the presence of an external trigger are excluded.
6. Known infection with human immunodeficiency virus (HIV) or treponema
7. Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections
8. Any suspected or known active infection
9. History of other diseases, metabolic dysfunctions, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications
10. Residual CD19+ B cells in BET final cell product ≥0.5%