Phase I Trial of Loncastuximab Tesirine and Venetoclax for Treatment of Relapsed/ Refractory Non-Hodgkin Lymphoma
Phase I Trial of Loncastuximab Tesirine and Venetoclax for Treatment of Relapsed/ Refractory Non-Hodgkin Lymphoma
The purpose of this study is to determine the correct dose and safety of combining two new cancer drugs, loncastuximab tesirine and venetoclax, as a treatment for relapsed or refractory B cell lymphoma.These drugs are used to treat some lymphomas, but have not yet been tested in combination for the treatment of lymphoma. The main goal of this study is to determine the safety of the combination.
This is a phase I trial designed to evaluate the safety and tolerability of loncastuximab tesirine given in combination with venetoclax for treatment of relapsed/refractory non - Hodgkin lymphoma.
Loncastuximab tesirine is an investigational (experimental) drug that works by targeting a protein in cancer cells (called CD19) and delivering a small amount of chemotherapy directly to the cancer cells. Loncastuximab tesirine is experimental because it is not approved by the Food and Drug Administration (FDA). Venetoclax, is a targeted anti-cancer drug, which works by imitating a particular protein produced by the tumor and interrupting its normal processes, ultimately causing the tumor cells to die. Adding venetoclax to the loncastuximab tesirine regimen is believed to increase the chance of getting relapsed or refractory B cell lymphoma cancer in remission. Venetoclax is approved by the FDA for treatment in some types of cancer, but is not approved by the FDA for the treatment of lymphoma soit is considered experimental in this study. Up to 36 subjects will take in this phase I research study.
The primary objective for this study: To determine the safety and tolerability of the combination of loncastuximab tesirine and venetoclax to identify the recommended phase 2 dose (RP2D) of these agents.
Secondary objectives are:
Inclusion Criteria:
Participants must have histologic or cytologic diagnosis of non-Hodgkin lymphoma, with the exclusion of small lymphocytic lymphoma/chronic lymphocytic leukemia.
--Patients with mantle cell lymphoma are not eligible for the dose escalation part of the study. Inclusion of patients with mantle cell lymphoma to the dose expansion part of the study will be done after an amendment delineates a MCL - specific venetoclax ramp up and tumor lysis syndrome prophylaxis and monitoring regimen.
Participants must have received ≥2 prior systemic therapies for their lymphoma.
Participants must have measurable disease as defined by the 2014 Lugano Classification.
Participants must meet clinical indications for treatment.
ECOG performance status ≤ 2 (see Appendix I)
Adequate bone marrow function, defined by the following laboratory parameters
Adequate organ function, defined by the following laboratory parameters
Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
-For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
--With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of loncastuximab. Men must refrain from donating sperm during this same period.
With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of loncastuximab to avoid exposing the embryo.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Exclusion Criteria:
Prior treatment toxicities not resolved to grade <2 according to NCI CTCAE 5.0 (with the exception of alopecia or grade 2 sensory peripheral neuropathy).
Patients with spontaneous tumor lysis syndrome.
Autologous stem cell transplant within 30 days of start of study drug (C1D1).
Allogeneic stem cell transplant within 60 days of start of study drug (C1D1).
Women who are pregnant or breastfeeding.
Active graft versus host disease
Active autoimmune disease
Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus. Note: Testing is not mandatory to be eligible.
Malabsorption syndrome or other condition that precludes enteral route of administration.
Known allergy to both xanthine oxidase inhibitors and rasburicase. Allergy to only one of these agents does not constitute an exclusion criterion.
Use of strong CYP3A inhibitors or inducers.
• All medications that fall in these categories should be discontinued 14 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
Administration or consumption of any of the following within 3 days prior to the first dose of study drug:
Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: