A Phase 1 interventional study of Loncastuximab tesirine and Venetoclax in Relapsed Non Hodgkin Lymphoma and Refractory Non-Hodgkin Lymphoma, sponsored by Paolo Caimi, MD. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-05.
Sponsored by Paolo Caimi, MD · Phase 1, Interventional, and Treatment
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:
1,989 studies on the registry are indexed under Lymphoma, Non-Hodgkin; 307 are open to participants now.
This study's enrollment of 23 is below the median of 41 across 1,703 interventional studies indexed under Lymphoma, Non-Hodgkin.
Browse Lymphoma, Non-Hodgkin studies →Paolo Caimi, MD is the lead sponsor of 5 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
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:
Use of strong CYP3A inhibitors or inducers.
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:
Participants will receive a baseline disease assessment via PET/CT in FDG avid lymphomas; CT scan (chest, abdomen, pelvis; inclusion of neck in selected cases). Bome marrow biopsy in selected cases. Premedication includes: * Allopurinol (to reduce uric acid) 300mg orally daily starting day -1 and continuing at least until day 7 of each cycle. * Dexamethasone (steroid pre-medication) 4mg orally twice daily on day -1, day 1 and day 2 of each cycle. * Adequate oral hydration starting on day -1 or -2, defined as 1 - 2 liters of oral intake of liquids in 24 hours Study treatment to be given every 21 days. * Loncastuximab tesirine (50 - 150 μg/kg) intravenously (IV) on day 1 of each 21-day cycle * Venetoclax (400 - 800 mg) orally, every day on days 1 - 5 of each 21-day cycle. Dose ramp-up on cycle 1 (over days 1 - 5 for target dose 400mg, 1 - 6 for target dose 600mg and 1 - 7 for target dose 800mg
Drug: Loncastuximab tesirine · Drug: Venetoclax
Loncastuximab tesirine 50 - 150 μg/kg will be administered as a 30 minutes IV infusion on Day 1 of each cycle for 6 cycles. On doses over 100 μg/kg, subsequent dosing (i.e. beyond 100 μg/kg) will be done at 50% of the dose that is administered on the first 2 cycles.
Also known as: ADCT-402, lonca
Participants will receive venetoclax at target doses of 400 - 800mg orally on days 1 - 5 of each (21 day) cycle. On cycle 1, venetoclax dose will be escalated to reach the target dose over the course of 5 days for target dose 400mg, 6 days for target dose 600mg and 7 days for target dose 800mg Venetoclax should preferably be given after a meal and on cycle 1 should be preceded by prophylaxis for tumor lysis syndrome (TLS).
Also known as: ABT-199, GDC-0199
Dose limiting toxicities (DLTs) during cycle 1 of loncastuximab tesirine and venetoclax
Number of DLTs during cycle 1 (21 days) of loncastuximab tesirine and venetoclax
Time frame: Up to Day 21
Maximum tolerated dose (MTD) of loncastuximab tesirine and venetoclax
Number of MTDs of loncastuximab tesirine and venetoclax
Time frame: 6 weeks
Overall response rate (ORR) as measured by proportion of participants with Complete Response (CR) and Partial Response (PR)
ORR, described as proportion of participants with CR and PR. Response assessed via Revised Response Criteria for Malignant Lymphoma
Time frame: Day 5 of cycle 1 (each cycle is 21 days)
Overall response rate (ORR) as measured by proportion of participants with CR or PR
ORR, described as proportion of participants with CR and PR. Response assessed via Revised Response Criteria for Malignant Lymphoma
Time frame: Between cycle 3 and 4 (21-day cycles) +/- 7 days
Overall response rate (ORR) as measured by proportion of participants with CR or PR
ORR, described as proportion of participants with CR and PR. Response assessed via Revised Response Criteria for Malignant Lymphoma
Time frame: End of treatment, aproximately day 84 +/- 7 days
Overall response rate (ORR)
ORR, described as a proportion. Response assessed via Revised Response Criteria for Malignant Lymphoma
Time frame: Followup, every 3 months up to one year after end of treatment
Complete response rate (CRR) as measured by proportion of participants with CR
ORR, described as a proportion. Response assessed via Revised Response Criteria for Malignant Lymphoma
Time frame: Day 5 of cycle 1 (each cycle is 21 days)
Complete response rate (CRR)
ORR, described as a proportion. Response assessed via Revised Response Criteria for Malignant Lymphoma
Time frame: Between cycle 3 and 4 (21-day cycles) +/- 7 days
Complete response rate (CRR)
ORR, described as a proportion. Response assessed via Revised Response Criteria for Malignant Lymphoma
Time frame: End of treatment, aproximately day 84 +/- 7 days
Complete response rate (CRR)
ORR, described as a proportion. Response assessed via Revised Response Criteria for Malignant Lymphoma
Time frame: Followup, every 3 months up to one year after end of treatment
Overall survival (OS)
OS is defined as the time from the date of study entry to the date of death, with censoring done on live patients at the time of last follow up. OS will be estimated using the Kaplan Meier method
Time frame: At end of follow-up (1 year)
Progression free survival (PFS)
PFS is defined as the time from entry onto study until lymphoma progression or death from any cause. PFS will be estimated using the Kaplan Meier method The precise date of progression is generally unknown. It may be defined as the first date of documentation of a new lesion or enlargement of a previous lesion, or the date of the scheduled clinic visit immediately after radiologic assessment has been completed. Where there is missing information, censoring of the data may be defined as the last date at which progression status was adequately assessed or the first date of unscheduled new anti-lymphoma treatment.
Time frame: At end of follow-up (1 year)
Median disease-free survival
Disease-free survival is measured from the time of occurrence of disease-free state (e.g. the adjuvant setting following surgery or radiation therapy) or attainment of a complete remission) to disease recurrence or death from lymphoma or acute toxicity of treatment.
Time frame: At end of follow-up (1 year)
Median disease-specific survival
Disease-specific survival is defined as death from lymphoma, or from toxicity from the drug. Death from unknown causes should be attributed to the drug
Time frame: At end of follow-up (1 year)
Time-to-treatment failure
Time to treatment failure (event-free survival) is measured from the time from study entry to any treatment failure including discontinuation of treatment for any reason, such as disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death.
Time frame: At end of follow-up (1 year)
Total number of adverse events during and after treatment
The objective is to describe the adverse event profile of the combination therapy by reporting number of adverse events during and after treatment, described as a proportion
Time frame: At end of treatment (21-day cycles until disease progression or toxicity, up to 6 cycles max)
Duration of response (DOR)
DOR, as measured by the median time in months of from first response (PR or CR) until relapse or death, using Kaplan Meier
Time frame: At end of follow-up (1 year)
Time to Progression (TTP)
TTP as measured by median time in months from treatment to death or relapse
Time frame: At end of follow-up (1 year)
Partial response rate (PRR)
PRR, as measured by proportion of patients with partial response
Time frame: At end of follow-up (1 year)
Plan to share: No — No plans to share Individual Participant Data (IPD)
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This study is active, not recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Paolo Caimi, MD