Loncastuximab Tesirine and Rituximab Followed by DA-EPOCH-R for Treating Patients With High-Risk Diffuse Large B-cell Lymphoma

NCT05600686 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: UCDCC#303NCI-2022-07762P30CA093373
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial evaluates whether loncastuximab tesirine and rituximab followed by dose-adjusted doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone works to treat patients with high risk diffuse large B-cell lymphoma. Loncastuximab tesirine is a monoclonal antibody called loncastuximab, linked to a drug called tesirine. It is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD19 receptors, and delivers tesirine to kill them. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Chemotherapy drugs such as doxorubicin, vincristine, and cyclophosphamide work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving loncastuximab tesirine and rituximab in combination with dose-adjusted doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone may be more effective at treating high risk diffuse large B-cell lymphoma patients than standard treatments.

Conditions

Double-Expressor Lymphoma; High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements; High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements

Outcome Measures

Primary Outcomes (1)

• Complete response rate

  Evaluated per 2014 Lugano criteria. An exact 95% confidence interval will be calculated.

  First dose through cycle 2 (1 cycle = 3 weeks)

Secondary Outcomes (4)

• Overall survival rate

  First dose to off study, assessed up to 3 years

• Relapse/progression free survival

  First dose (cycle 1 day 6 rituximab dose) until relapse/progression or off study, whichever occurs first, assessed up to 3 years

• Overall response rate (complete response + partial response)

  First dose through cycle 2 (1 cycle = 3 weeks)

• Incidence of adverse events

  First dose through 30 days post last dose

Study Arms (1)

Treatment (Lonca-R, DA-EPOCH-R)

EXPERIMENTAL

Patients receive rituximab IV, loncastuximab tesirine IV, etoposide IV, doxorubicin IV, vincristine IV, prednisone PO, and cyclophosphamide IV on study. Patients also undergo collection of blood samples and bone marrow aspiration and biopsy at screening and CT or PET/CT at screening, throughout the study, and during follow up.

Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Etoposide; Biological: Loncastuximab Tesirine; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (Lonca-R, DA-EPOCH-R)

Doxorubicin DRUG

Given IV

Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Treatment (Lonca-R, DA-EPOCH-R)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16

Treatment (Lonca-R, DA-EPOCH-R)

Loncastuximab Tesirine BIOLOGICAL

Given IV

Also known as: ADC ADCT-402, ADCT-402, Anti-CD19 PBD-conjugate ADCT-402, Loncastuximab Tesirine-lpyl, Zynlonta

Treatment (Lonca-R, DA-EPOCH-R)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Treatment (Lonca-R, DA-EPOCH-R)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Riabni, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, rituximab-abbs, Rituximab-arrx, Rituximab-pvvr, RTXM83, Ruxience, Truxima

Treatment (Lonca-R, DA-EPOCH-R)

Vincristine DRUG

Given IV

Also known as: Leurocristine, VCR, Vincrystine

Treatment (Lonca-R, DA-EPOCH-R)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed untreated DEL and DHL diffuse large B-cell lymphoma (DLBCL) meeting the World Health Organization (WHO) criteria for DEL - MYC greater than 40% and BCL2 greater than 50% by immunohistochemistry, or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit and/or triple-hit are included)
• Measurable disease by CT or PET/CT scan, with one or more sites of disease \>= 1.5 cm in longest dimension
• Age \>= 18 years at time of consent
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy \>= 6 months
• Leukocytes \>= 2,500/uL
• Absolute neutrophil count \>= 1,000/uL
• Platelets \>= 100,000/uL
• Hemoglobin \>= 8 g/dL
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN (AST and/or ALT =\< 5 x ULN for patients with liver involvement)
• Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN for patients with documented liver involvement or bone metastases)
• Creatinine clearance \>= 30 mL/min by Cockcroft-Gault
• Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
• Transthoracic echocardiography (TTE) or multigated acquisition scan (MUGA) ejection fraction greater than 40%

You may not qualify if:

• Current/ prior use of:
• Lymphoma treatment, except for:
• cycle of DA-EPOCH-R or rituximab, cyclophosphamide, doxorubicin (Adriamycin) vincristine (Oncovin) and prednisolone (R-CHOP)
• Radiotherapy \> 2 weeks of initiating study treatment
• Nitrosoureas or mitomycin C \> 6 weeks of initiating study treatment
• Steroid treatment for DLBCL or steroid monotherapy to stabilize disease while awaiting fluorescence in situ hybridization (FISH)
• Other cancer therapies (e.g., prostate, breast hormonal-based therapy) per the principal investigator's discretion
• Anthracycline greater than 50 mg/m\^2 (total lifetime) for a prior malignancy
• Complementary and alternative medications (CAM) within 1 week prior to initiating study treatment
• Treatment with any other investigational agent for any indication within 3 weeks prior to initiating study treatment
• Loncastuximab tesirine or rituximab with progression within 6 months of initiating study treatment
• Oral or intravenous (IV) antibiotics within 2 weeks prior to initiating study treatment. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
• Live, attenuated influenza vaccine within 4 weeks prior to initiating study treatment
• Immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor, such as anti-tumor necrosis factor \[TNF\] agents) within 14 days prior to initiating study treatment. The following are exceptions to this criterion:
• Steroids

Sponsors & Collaborators

• Joseph Tuscano: lead
• National Cancer Institute (NCI): collaborator
• ADC Therapeutics S.A.: collaborator

Study Sites (2)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

UC San Diego Moores Cancer Center

San Diego, California, 92037, United States

RECRUITING

MeSH Terms

Interventions

Cyclophosphamide; Doxorubicin; Etoposide; loncastuximab tesirine; Prednisone; deltacortene; prednylidene; Rituximab; CT-P10; Vincristine

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Joseph M Tuscano

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joseph M Tuscano

CONTACT

916-734-3771; jtuscano@ucdavis.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: October 10, 2022
• First Posted: October 31, 2022
• Study Start: May 24, 2023
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2028
• Last Updated: November 25, 2025

Record last verified: 2025-11

Locations

US (2)