Loncastuximab Tesirine + Chemotherapy for Lymphoma

(LONCA Trial)

Recruiting at 2 trial locations

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Medical College of Wisconsin

Must not be taking: Antivirals

Disqualifiers: Effusions, Hepatitis, Infections, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

11 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for people with aggressive B-cell lymphoma, a type of blood cancer. The goal is to find the safest and most effective dose of loncastuximab tesirine (an antibody-drug conjugate) when combined with chemotherapy medications. People newly diagnosed with aggressive B-cell lymphomas who haven't received multi-agent chemotherapy before may be suitable for this study. The trial aims to assess the drug's effectiveness and safety for future treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, corticosteroid therapy is allowed without a washout period, and prephase treatment with certain drugs is permitted for symptomatic patients.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that loncastuximab tesirine, a treatment for certain types of lymphoma, has some common side effects. In studies with 215 patients, more than 20% experienced low platelet counts (thrombocytopenia) and increased liver enzymes. Serious side effects, such as fever with low white blood cell counts (febrile neutropenia) and infections like pneumonia, occurred in about 2% of patients.

This treatment is being tested with a chemotherapy regimen called DA-EPOCH-R, which includes drugs like cyclophosphamide and doxorubicin. These well-known chemotherapy drugs have established safety records. The current clinical trial is in its early phase, focusing on finding the safe dose level for this combination. This phase aims to ensure the treatment's safety and to determine the best dose for future use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Loncastuximab Tesirine for lymphoma because it represents a novel approach in targeting cancer cells. Unlike standard chemotherapy drugs like Cyclophosphamide or Doxorubicin, which attack all rapidly dividing cells, Loncastuximab Tesirine specifically targets the CD19 protein found on the surface of certain lymphoma cells. This targeted approach could potentially mean fewer side effects and a more effective attack on the cancer itself. Additionally, by combining this targeted therapy with other chemotherapy agents, the treatment might enhance overall effectiveness against lymphoma.

What evidence suggests that this trial's treatments could be effective for aggressive B-cell lymphoid malignancies?

Research has shown that loncastuximab tesirine, also known as ZYNLONTA®, holds promise for treating certain aggressive lymphomas. In earlier studies, this treatment achieved an impressive overall response rate, with up to 85% of patients experiencing cancer shrinkage or disappearance. Specifically, about 69% of patients had a complete response, where their cancer became undetectable after treatment. In this trial, participants will receive varying doses of loncastuximab tesirine to determine the most effective and safe dosage. These findings suggest that loncastuximab tesirine could be an effective option for patients with hard-to-treat lymphomas. ^{6 7 8 9 10}

Who Is on the Research Team?

Mehdi Hamadani, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

Adults over 18 with specific types of B-cell lymphoma who haven't had multiagent chemotherapy. They can have limited radiation or corticosteroid therapy, and must be physically able to perform daily activities (ECOG 0-3). Their major organs need to function well, they can't be pregnant or breastfeeding, and shouldn't have severe allergies to the study drugs.

Inclusion Criteria

Adequate hematological function: ANC ≥1 × 103/μL and platelet count ≥50 x 10^3/μL

My liver tests are within normal limits, or any high results are due to my condition or Gilbert's syndrome.

Ability to understand a written informed consent document, and the willingness to sign it

Exclusion Criteria

Breastfeeding or pregnant

I have chronic hepatitis B but can't or won't take standard antiviral treatments, yet my virus levels are undetectable.

My liver function is severely impaired.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1a involves a 3+3 dose escalation design to find the maximum tolerated dose (MTD) of loncastuximab tesirine in combination with DA-EPOCH-R.

Up to 21 days per cycle

Cohort Expansion

Phase 1b involves a cohort expansion at the dose level determined to be the recommended phase 2 dose.

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Etoposide
• Loncastuximab Tesirine
• Prednisone
• Rituximab
• Vincristine

Trial Overview The trial is testing different doses of Loncastuximab Tesirine combined with DA-EPOCH-R chemotherapy in patients with aggressive B-cell lymphomas. The goal is to find the highest dose that's safe and tolerable without causing too many side effects.

How Is the Trial Designed?

Group I: Loncastuximab Tesirine Dose Escalation Maximum Tolerated Dose Experimental Treatment 9 Interventions

The study uses a classic 3+3 dose-escalation design. Three patients will be enrolled into a cohort receiving 0.075 mg/kg by IV. If there is no dose-limiting toxicity (DLT) seen in any of these participants, the trial will enroll additional participants into the next higher dose cohort, which is 0.12 mg/kg by IV. If one patient experiences a DLT at a specific dose, an additional three individuals will be accrued into that same dose cohort. The third dose level is 0.15 mg/kg by IV. DLTs in two or more at a specific dose level indicates that the MTD has been exceeded; dose escalation will not be pursued, and the prior dose level will be expanded to six patients; if there is no more than one patient who experiences a DLT among those six patients, that dose level is considered the MTD. This dose will be added to this record when it is determined.

Group II: Loncastuximab Tesirine Dose Escalation 0.15 mg/kg by IV. Experimental Treatment 7 Interventions

The study uses a classic 3+3 dose-escalation design. Three patients will be enrolled into a cohort receiving 0.075 mg/kg by IV. If there is no dose-limiting toxicity (DLT) seen in any of these participants, the trial will enroll additional participants into the next higher dose cohort, which is 0.12 mg/kg by IV. If one patient experiences a DLT at a specific dose, an additional three individuals will be accrued into that same dose cohort. The third dose level is 0.15 mg/kg by IV. DLTs in two or more at a specific dose level indicates that the MTD has been exceeded; dose escalation will not be pursued, and the prior dose level will be expanded to six patients; if there is no more than one patient who experiences a DLT among those six patients, that dose level is considered the MTD.

Group III: Loncastuximab Tesirine Dose Escalation 0.12 mg/kg by IV. Experimental Treatment 7 Interventions

The study uses a classic 3+3 dose-escalation design. Three patients will be enrolled into a cohort receiving 0.075 mg/kg by IV. If there is no dose-limiting toxicity (DLT) seen in any of these participants, the trial will enroll additional participants into the next higher dose cohort, which is 0.12 mg/kg by IV. If one patient experiences a DLT at a specific dose, an additional three individuals will be accrued into that same dose cohort. The third dose level is 0.15 mg/kg by IV. DLTs in two or more at a specific dose level indicates that the MTD has been exceeded; dose escalation will not be pursued, and the prior dose level will be expanded to six patients; if there is no more than one patient who experiences a DLT among those six patients, that dose level is considered the MTD.

Group IV: Loncastuximab Tesirine Dose Escalation 0.075 mg/kg by IV. Experimental Treatment 7 Interventions

The study uses a classic 3+3 dose-escalation design. Three patients will be enrolled into a cohort receiving 0.075 mg/kg by IV. If there is no dose-limiting toxicity (DLT) seen in any of these participants, the trial will enroll additional participants into the next higher dose cohort, which is 0.12 mg/kg by IV. If one patient experiences a DLT at a specific dose, an additional three individuals will be accrued into that same dose cohort. The third dose level is 0.15 mg/kg by IV. DLTs in two or more at a specific dose level indicates that the MTD has been exceeded; dose escalation will not be pursued, and the prior dose level will be expanded to six patients; if there is no more than one patient who experiences a DLT among those six patients, that dose level is considered the MTD.

Group V: Dose Expansion Phase Experimental Treatment 9 Interventions

Subjects will receive the recommended phase 2 dose (RP2D) identified from dose-escalation phase. This dose will be added to this record when it is determined.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

Etoposide is a key drug in treating malignant lymphomas and Hodgkin's disease, showing broad activity across various subtypes and demonstrating single-agent efficacy comparable to older treatments like alkylating agents and doxorubicin.

The drug works by inhibiting protein synthesis and topoisomerase II, allowing it to provide effective cytotoxicity without cross-resistance, and is integrated into multiple treatment protocols, enhancing the overall management of these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of etoposide in the management of lymphomas and Hodgkin's disease. O'Reilly, SE., Klimo, P., Connors, JM.[2019]

In a study involving 307 cancer patients, dolasetron mesylate effectively prevented nausea and vomiting during chemotherapy, with a significant increase in complete response rates from 44.7% at 25 mg to 82.5% at 200 mg.

All doses of dolasetron were well tolerated, with the most common side effects being headache and dizziness, indicating a favorable safety profile for this antiemetic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral dolasetron mesylate in patients receiving moderately emetogenic platinum-containing chemotherapy. Oral Dolasetron Dose Response Study Group. Grote, TH., Pineda, LF., Figlin, RA., et al.[2013]

In a study involving 319 cancer patients, dolasetron mesylate was shown to be effective in preventing nausea and vomiting after chemotherapy, with higher doses leading to better outcomes.

No serious side effects were reported, and the most common adverse effect was a mild headache, indicating that dolasetron mesylate is a safe option for managing chemotherapy-induced nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double blind, dose-response trial across four oral doses of dolasetron for the prevention of acute emesis after moderately emetogenic chemotherapy. Oral Dolasetron Dose-Response Study Group. Rubenstein, EB., Gralla, RJ., Hainsworth, JD., et al.[2013]

In a study involving 197 patients undergoing high-dose chemotherapy, dolasetron and ondansetron were found to be equally effective in preventing nausea and vomiting, with total response rates of 45.7% for dolasetron and 46.9% for ondansetron.

Both dolasetron and ondansetron were well-tolerated by patients, indicating that they are safe options for managing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, multicenter, open-label comparison of the antiemetic efficacy of dolasetron versus ondansetron for the prevention of nausea and vomiting during high-dose myeloablative chemotherapy. Mandanas, RA., Beveridge, R., Rifkin, RM., et al.[2020]

In a study of 304 Chinese breast cancer patients undergoing doxorubicin-cyclophosphamide chemotherapy, adding olanzapine to an aprepitant-based antiemetic regimen significantly improved the complete response rate and quality of life compared to a standard doublet regimen.

The netupitant/palonosetron/dexamethasone combination was found to be more effective than the aprepitant/ondansetron/dexamethasone regimen, indicating that the choice of antiemetic can greatly impact patient outcomes during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of optimal contemporary antiemetic prophylaxis for doxorubicin-cyclophosphamide chemotherapy in Chinese cancer patients: post-hoc analysis of 3 prospective studies. Yeo, W., Li, L., Lau, TK., et al.[2021]

In a study of 83 breast cancer patients undergoing chemotherapy with doxorubicin-cyclophosphamide, both aprepitant (APT) and olanzapine (OLP) were effective in preventing chemotherapy-induced nausea and vomiting, with complete response rates of 81% for APT and 85% for OLP in the acute period.

OLP showed a lower incidence of severe vomiting compared to APT, with 50% of OLP patients experiencing severe vomiting versus 81% in the APT group, suggesting that OLP may provide a safer profile for managing nausea and vomiting in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olanzapine versus aprepitant for the prophylaxis of chemotherapy-induced nausea and vomiting in breast cancer patients receiving doxorubicin-cyclophosphamide regimen: A prospective, nonrandomized, open-label study. Shivaprakash, G., Udupa, KS., Sarayu, V., et al.[2018]

In a study of 415 patients with low-grade lymphoma treated with doxorubicin-containing therapy (CHOP), the median survival duration was 6.9 years, with significant factors affecting survival including age, sex, and histology.

The study found that doxorubicin-containing treatment did not improve overall median survival compared to less aggressive treatment options, and maintenance therapy did not extend survival for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients with low-grade malignant lymphomas treated with doxorubicin-based chemotherapy or chemoimmunotherapy. Dana, BW., Dahlberg, S., Nathwani, BN., et al.[2017]

A novel chemotherapy regimen for treating intermediate and high-grade non-Hodgkin's lymphoma resulted in a high complete response rate of 77% among 56 previously untreated patients, indicating its efficacy in a population with a poor prognosis.

Despite the promising response rates, the treatment was associated with significant myelosuppression, with severe leukopenia occurring in all patients and a 9% rate of toxic deaths, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of treatment with high intensity, brief duration chemotherapy in poor prognosis non-Hodgkin's lymphoma. McMaster, ML., Greer, JP., Wolff, SN., et al.[2019]

In a study of 22 patients with non-Hodgkin's lymphoma, the LEMP regimen (oral lomustine, i.v. etoposide, methotrexate, and prednisone) resulted in 5 complete remissions and 12 partial remissions, demonstrating its efficacy in patients who had previously undergone chemotherapy.

The treatment was well tolerated with minimal toxicity, showing no alopecia or cardiotoxicity, and no treatment-related deaths, suggesting it could be a safer option for patients unable to handle more intensive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lomustine, etoposide, methotrexate and prednisone (LEMP) therapy for relapsed and refractory non-Hodgkin's lymphoma. Dorigo, A., Mansberg, R., Kwan, YL.[2019]

Anthracyclines, particularly doxorubicin, are crucial in treating non-Hodgkin's lymphoma (NHL), with the CHOP regimen being the standard for over 20 years, but they carry a risk of cardiotoxicity as a late side effect.

Using liposome-encapsulated doxorubicin has shown to be effective in treating NHL while significantly reducing the risk of cardiotoxicity, making it a safer option for patients, especially those at higher risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moving forward with new data and approaches: a fresh look at anthracyclines in non-Hodgkin's lymphoma. Amadori, D.[2023]

In a study of 35 adults with relapsed or refractory B-cell acute lymphoblastic leukemia, loncastuximab tesirine, an antibody-drug conjugate targeting CD19, showed promising preliminary clinical activity with 3 patients achieving complete responses at different doses.

The treatment was generally well-tolerated, with common side effects including nausea and febrile neutropenia, but no treatment-related deaths were reported, indicating a favorable safety profile despite a high incidence of grade ≥3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine, an anti-CD19 antibody-drug conjugate, in relapsed/refractory B-cell acute lymphoblastic leukemia. Jain, N., Stock, W., Zeidan, A., et al.[2023]

In a phase 1 study involving 183 patients with relapsed or refractory B-cell non-Hodgkin lymphoma, loncastuximab tesirine demonstrated a promising overall response rate of 45.6%, with 26.7% achieving complete responses, indicating its potential as an effective treatment option.

The study established a recommended dose of 150 µg/kg for phase 2 trials, with an acceptable safety profile characterized by manageable hematologic toxicities, suggesting that loncastuximab tesirine could be a viable alternative to current therapies for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Hamadani, M., Radford, J., Carlo-Stella, C., et al.[2022]

In a study of 91 people living with HIV and Burkitt lymphoma, adding rituximab to CODOX-M/IVAC chemotherapy did not increase severe treatment-related toxicities, indicating it is a safe option for this population.

The addition of rituximab significantly improved both overall survival (72% vs. 55%) and progression-free survival (81% vs. 55%) compared to chemotherapy alone, suggesting it enhances treatment efficacy without added risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. Alwan, F., He, A., Montoto, S., et al.[2022]

In a study involving 80 patients from the LOTIS-2 trial, loncastuximab tesirine (Lonca) demonstrated a significantly higher overall response rate (53.4%) compared to chemoimmunotherapy (CIT) treatments (40.3%) for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).

Lonca also showed improved overall survival, with a median survival of 10.8 months compared to 6.4 months for CIT, indicating it may be a more effective treatment option for patients with R/R DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparison of the Efficacy of Loncastuximab Tesirine Versus Treatment in the Chemoimmunotherapy Era for Relapsed/Refractory Diffuse Large B-cell Lymphoma. Hamadani, M., Chen, L., Song, Y., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37646659/

long-term efficacy and safety from the phase II LOTIS-2 study Lonca continued to demonstrate durable, long-term responses with manageable safety and tolerability in patients with CR.

2. zynlonta.com zynlonta.com/study-results/

Study Results | ZYNLONTA® (loncastuximab tesirine-lpyl ... ZYNLONTA® was effective for many people who had past R/R DLBCL therapies. The ZYNLONTA® clinical trial included people who had already received a variety of ...

3. haematologica.org haematologica.org/article/view/haematol.2023.283459

long-term efficacy and safety from the phase II LOTIS-2 study Lonca demonstrated single-agent antitumor activity and had an acceptable safety profile in heavily pretreated patients with R/R DLBCL with an overall response ...

4. ir.adctherapeutics.com ir.adctherapeutics.com/press-releases/press-release-details/2025/ADC-Therapeutics-Announces-Updated-ZYNLONTA-Investigator-Initiated-Trial-Data-in-RR-Marginal-Zone-Lymphoma-Presented-at-18th-International-Conference-on-Malignant-Lymphoma-ICML/default.aspx

Press Release Details Updated Phase 2 data evaluating ZYNLONTA as a monotherapy demonstrate overall response rate (ORR) of 85% and complete response (CR) rate of 69%.

5. ashpublications.org ashpublications.org/bloodadvances/article/8/1/93/498392/Clinical-outcomes-of-older-and-younger-patients

Clinical outcomes of older and younger patients treated with ... The pivotal LOTIS-2 study demonstrated an overall response rate (ORR) of 48.3% with durable responses in a heavily pretreated, difficult-to- ...

6. zynlontahcp.com zynlontahcp.com/safety

Safety Profile - loncastuximab tesirine-lpyl (ZYNLONTA The most common serious adverse reactions that occurred in ≥2% of patients were febrile neutropenia, pneumonia, edema, pleural effusion, and sepsis.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761196s000lbl.pdf

loncastuximab tesirine-lpyl - accessdata.fda.gov In this pooled safety population of 215 patients, the most common (>20%) adverse reactions, including laboratory abnormalities, were thrombocytopenia, increased ...

8. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.34816

Safety of loncastuximab tesirine‐lpyl in diffuse large B‐cell ... The authors present two cases of r/r DLBCL safely treated with full-dose loncastuximab tesirine-lpyl in the setting of severe hepatic dysfunction.

9. mayoclinic.org mayoclinic.org/drugs-supplements/loncastuximab-tesirine-lpyl-intravenous-route/description/drg-20514884

Loncastuximab tesirine-lpyl (intravenous route) Loncastuximab tesirine-lpyl injection is to treat large B-cell lymphoma ... Safety and efficacy have not been established. Geriatric.

10. zynlonta.com zynlonta.com/resources/

Resources | ZYNLONTA® (loncastuximab tesirine-lpyl) Patient ... Important Safety Information ... ZYNLONTA® is a prescription medicine used to treat adults with certain types of large B-cell lymphoma that has come back ( ...