Loncastuximab Tesirine and Venetoclax for Relapsed/ Refractory Non-Hodgkin Lymphoma

NCT05053659 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE5420
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Refractory Non-Hodgkin Lymphoma; Relapsed Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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

  Up to Day 21

• Maximum tolerated dose (MTD) of loncastuximab tesirine and venetoclax

  Number of MTDs of loncastuximab tesirine and venetoclax

  6 weeks

Secondary Outcomes (17)

• Overall response rate (ORR) as measured by proportion of participants with Complete Response (CR) and Partial Response (PR)

  Day 5 of cycle 1 (each cycle is 21 days)

• Overall response rate (ORR) as measured by proportion of participants with CR or PR

  Between cycle 3 and 4 (21-day cycles) +/- 7 days

• Overall response rate (ORR) as measured by proportion of participants with CR or PR

  End of treatment, aproximately day 84 +/- 7 days

• Overall response rate (ORR)

  Followup, every 3 months up to one year after end of treatment

• Complete response rate (CRR) as measured by proportion of participants with CR

  Day 5 of cycle 1 (each cycle is 21 days)

Study Arms (1)

Loncastuximab tesirine & venetoclax

EXPERIMENTAL

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

Interventions

Venetoclax DRUG

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

Loncastuximab tesirine & venetoclax

Loncastuximab tesirine DRUG

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

Loncastuximab tesirine & venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Absolute neutrophil count of 1.0 x 109/L
• Platelet count of 75 x 109/L; platelet count of 50 - 75 x 109/L are permitted in participants with marrow involvement by the lymphoma. Platelets must not have received a platelet transfusion in 7 days.
• Adequate organ function, defined by the following laboratory parameters
• Adequate hepatic function, with transaminases (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], and gamma glutammyltransferase \[GGT\]) ≤ 2.5 times the upper limit of normal;
• Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
• Calculated creatinine clearance \> 30 mL/min by the Cockcroft-Gault equation.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \< 1% per year during the treatment period and for at least 30 days after the last dose of venetoclax and at least 9 months after the last dose of loncastuximab tesirine for women.
• A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
• 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.

You may not qualify if:

• 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.
• 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:
• Grapefruit or grapefruit products
• Seville oranges (including marmalade containing Seville oranges)
• Star fruit

Sponsors & Collaborators

• Paolo Caimi, MD: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

loncastuximab tesirine; venetoclax

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Paolo Caimi, MD

  Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: September 22, 2021
• Study Start: June 20, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)