36 Participants Needed

Loncastuximab Tesirine + Venetoclax for Non-Hodgkin's Lymphoma

BH
PC
Overseen ByPaolo Caimi, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Do I need to stop taking my current medications for the trial?

The trial requires you to stop taking strong CYP3A inhibitors or inducers at least 14 days or 5 half-lives before starting the study drugs. If you're on these medications, you'll need to discontinue them before participating.

What data supports the effectiveness of the drug Venetoclax for treating Non-Hodgkin's Lymphoma?

Venetoclax has shown effectiveness in treating chronic lymphocytic leukemia (CLL), achieving high response rates and longer progression-free survival when used alone or in combination with other drugs. This suggests potential effectiveness for similar blood cancers like Non-Hodgkin's Lymphoma.12345

Is the combination of Loncastuximab Tesirine and Venetoclax safe for humans?

Loncastuximab Tesirine has shown a tolerable safety profile in clinical trials for non-Hodgkin's lymphoma, with side effects like low white blood cell counts, low platelet counts, and elevated liver enzymes. Venetoclax is generally safe for chronic lymphocytic leukemia, with manageable side effects such as low white blood cell counts. Both drugs have been approved for use in specific conditions, indicating they are considered safe for humans in those contexts.12678

What makes the drug combination of Loncastuximab Tesirine and Venetoclax unique for treating Non-Hodgkin's Lymphoma?

This drug combination is unique because Loncastuximab Tesirine is an antibody-drug conjugate that targets CD19 on B cells, delivering a cytotoxic agent directly to cancer cells, while Venetoclax is a BCL-2 inhibitor that helps restore the natural process of cell death in cancer cells. Together, they offer a novel approach by combining targeted delivery with apoptosis restoration, which may enhance treatment effectiveness for Non-Hodgkin's Lymphoma.24567

What is the purpose of this trial?

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.

Research Team

PC

Paolo Caimi, MD

Principal Investigator

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with Non-Hodgkin Lymphoma who've had at least two prior treatments and still have measurable disease. They must be in a stable condition, not pregnant or breastfeeding, willing to use effective contraception, and without serious unresolved treatment side effects from previous therapies.

Inclusion Criteria

Participants must meet clinical indications for treatment
I agree to use birth control and not donate sperm.
I can take care of myself but might not be able to do heavy physical work.
See 6 more

Exclusion Criteria

I will have a stem cell transplant using my own cells within 30 days before starting the study drug.
I had a stem cell transplant from a donor within the last 60 days.
I cannot take drugs by mouth due to a digestive condition.
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive loncastuximab tesirine intravenously on day 1 and venetoclax orally on days 1-5 of each 21-day cycle, with premedication and hydration

Up to 18 weeks (6 cycles of 21 days each)
1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year
Every 3 months

Treatment Details

Interventions

  • Loncastuximab Tesirine
  • Venetoclax
Trial Overview The study tests combining loncastuximab tesirine with venetoclax to treat B cell lymphoma that has come back or hasn't responded to other treatments. The main focus is finding the right dose and checking if this drug combo is safe.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Loncastuximab tesirine & venetoclaxExperimental Treatment2 Interventions
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

Loncastuximab Tesirine is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Zynlonta for:
  • Diffuse large B-cell lymphoma (DLBCL)
  • DLBCL arising from low-grade lymphoma
  • High-grade B-cell lymphoma
🇪🇺
Approved in European Union as Zynlonta for:
  • Diffuse large B-cell lymphoma (DLBCL)
  • DLBCL arising from low-grade lymphoma
  • High-grade B-cell lymphoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Paolo Caimi, MD

Lead Sponsor

Trials
5
Recruited
170+

Brian Hill, MD, PhD

Lead Sponsor

Trials
3
Recruited
90+

Brian Hill

Lead Sponsor

Trials
2
Recruited
60+

Findings from Research

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.
While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia .Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]
In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.
Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia.Blair, HA.[2021]
A study involving 321 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) found that venetoclax (VEN) used alone (VENmono) and in combination with rituximab (VENcombo) showed similar overall response rates (81% for VENmono vs 84% for VENcombo) and no significant differences in progression-free survival (PFS) or overall survival (OS) after a median follow-up of 13.4 months.
The addition of the anti-CD20 antibody rituximab to venetoclax did not improve survival outcomes, indicating that VENmono may be as effective as VENcombo in this patient population, which had a high treatment burden.
A retrospective comparison of venetoclax alone or in combination with an anti-CD20 monoclonal antibody in R/R CLL.Mato, AR., Roeker, LE., Eyre, TA., et al.[2020]

References

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]
A retrospective comparison of venetoclax alone or in combination with an anti-CD20 monoclonal antibody in R/R CLL. [2020]
Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]
Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. [2018]
Loncastuximab Tesirine: First Approval. [2021]
Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a review of clinical data. [2022]
Loncastuximab tesirine for diffuse large B-cell lymphoma. [2021]
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