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Loncastuximab Tesirine in Combination With Chemotherapy Prior to Stem Cell Transplant for the Treatment of Recurrent or Refractory Diffuse Large B-Cell Lymphoma | Clinical Trials | Clareo Health

WITHDRAWNPHASE1

Loncastuximab Tesirine in Combination With Chemotherapy Prior to Stem Cell Transplant for the Treatment of Recurrent or Refractory Diffuse Large B-Cell Lymphoma

Loncastuximab Tesirine in Combination With BEAM (Carmustine, Etoposide, Ara-C, Melphalan) Conditioning Regimen Prior to Autologous Stem Cell Transplant (ASCT) and for Maintenance Therapy in Diffuse Large B-Cell Lymphoma (DLBCL)

NCT05228249•Fred Hutchinson Cancer Center

View on ClinicalTrials.gov

Summary

This phase I trial studies the side effects and best dose of loncastuximab tesirine in combination with carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy regimen in treating patients with diffuse large B-cell lymphoma that has come back (recurrent) or has not responded to treatment (refractory). Loncastuximab tesirine is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as carmustine, etoposide, cytarabine, and melphalan, 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. Giving chemotherapy with loncastuximab tesirine may kill more cancer cells.

Detailed Description

OUTLINE: This is a dose-escalation study of loncastuximab tesirine. PART I (CONDITIONING): Patients receive loncastuximab tesirine intravenously (IV) on day -7, carmustine IV over 2 hours on day -7, etoposide IV over 1-2 hours twice daily (BID) days -6, -5, -4, and -3, cytarabine IV over 1 hour BID on days -6, -5, -4, and -3, and melphalan IV over 15-20 minutes on day -2. Patients undergo peripheral blood ASCT per standard practice on day 0. PART II (MAINTENANCE): Beginning 30-90 days after ASCT, patients receive loncastuximab tesirine IV once every 3 weeks (Q3W) for up to 9 cycles in the absence of disease progression or unacceptable toxicity. After completion of the study treatment, patients are followed for 2 years.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•PART 1: Subjects must have a histologically confirmed diagnosis of diffuse large B-cell lymphoma including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma (with MYC and BCL-2 and/or BCL-6 gene rearrangement), and DLBCL arising from follicular lymphoma
•PART 1: Subjects must be eligible for high-dose therapy (BEAM conditioning chemotherapy) and autologous stem cell transplant, as determined by transplant center
•PART 1: Subjects must have chemosensitive disease as defined radiographically (positron emission tomography \[PET\]/computed tomography \[CT\] and/or diagnostic CT) by at least a partial response (PR) to their last cycle of salvage therapy, within 60 days of enrollment
•PART 1: Subjects must be \>= 18 years of age
•PART 1: Eastern Cooperative Oncology Group (ECOG) score =\< 2 or Karnofsky score \>= 60%
•PART 1: Creatinine clearance (CrCl) \> 40 mL/min by Cockcroft-Gault formula or serum creatinine =\< 2.0 mg/dL
•PART 1: Total bilirubin =\< 1.5 x the upper limit of normal (ULN) unless isolated hyperbilirubinemia attributed to Gilbert's syndrome; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN
•PART 1: Adequate pulmonary function, defined as lung carbon monoxide diffusing capability test (DLCO) (corrected or uncorrected for hemoglobin per institutional standards), forced expiratory volume in 1 (FEV1), forced vital capacity (FVC) \>= 50% of predicted
•PART 1: Cardiac: Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of \>= 50%. Patients 60 years or older must have an LVEF at rest \>= 40%, as measured by echocardiogram or radionuclide ventriculogram scan (MUGA)
•PART 1: Hematologic: Prothrombin time (PT)/international normalized ratio (INR) \< 1.5 x ULN and partial thromboplastin time PTT) (activated partial thromboplastin time \[aPTT\]) \< 1.5 x ULN, absolute neutrophil count (ANC) \>= 1000/mL, platelet \>= 75,000/uL
+11 more criteria

Exclusion Criteria

•PART 1: Receiving other investigational agents
•PART 1: History of central nervous system (CNS) involvement by lymphoma
•PART 1: If a history of receiving a CD19 targeting agent (e.g., CD19 directed CAR T-cell Kymriah, Yescarta, Breyanzi, CD19 antibody Monjuvi), must have pathologic evidence for CD19 expression after receiving CD19 targeting agent
•PART 1: History of immunogenicity or hypersensitivity to a CD19 antibody
•PART 1: Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement); symptomatic congestive heart failure unresponsive to treatment, unstable angina pectoris, symptomatic cardiac arrhythmia not including premature ventricular contractions (PVC); or psychiatric illness/social situations that would limit compliance with study requirements
•PART 1: Active autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis \[e.g., granulomatosis with polyangiitis\]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis); other central nervous system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis)
•PART 1: Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
•PART 1: Known seropositivity for human immunodeficiency virus (HIV), known history of hepatitis B or hepatitis C
•PART 1: Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the investigator(s) agreed and had documented that it was not exclusionary
•PART 1: Any other significant medical illness, abnormality, or condition that could, in the investigator(s)' judgment, make the patient inappropriate for study participation or could put the patient at risk
+1 more criteria

Locations (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Key Dates

Start Date

April 1, 2023

Primary Completion Date

October 1, 2025

Completion Date

October 1, 2027

Last Updated

January 13, 2023

Conditions

Recurrent Diffuse Large B-Cell LymphomaRecurrent Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 RearrangementsRecurrent Primary Mediastinal (Thymic) Large B-Cell LymphomaRecurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRefractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 RearrangementsRefractory Primary Mediastinal (Thymic) Large B-Cell LymphomaRefractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Interventions

Autologous Hematopoietic Stem Cell Transplantation

PROCEDURE

Carmustine

DRUG

Cytarabine

DRUG

Etoposide

DRUG

Loncastuximab Tesirine

BIOLOGICAL

Melphalan

DRUG

Tegavivint for Treating Patients With Relapsed or Refractory Large B-Cell Lymphoma

NCT05755087

Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell TypeRecurrent Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type+7 more

View study

RECRUITINGPHASE2

Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

NCT05672251

Recurrent Diffuse Large B-Cell LymphomaRecurrent Grade 3b Follicular Lymphoma+10 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 13, 2023Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Loncastuximab Tesirine in Combination With Chemotherapy Prior to Stem Cell Transplant for the Treatment of Recurrent or Refractory Diffuse Large B-Cell Lymphoma

Inclusion Criteria

Exclusion Criteria

Tegavivint for Treating Patients With Relapsed or Refractory Large B-Cell Lymphoma

Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Epcoritamab Plus Standard of Care Platinum-Based Chemotherapy and Autologous Hematopoietic Cell Transplant for the Treatment of Relapsed or Refractory Large B-cell Lymphoma

Zanubrutinib in Combination With Sonrotoclax for the Treatment of Underrepresented Ethnic and Racial Minorities With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Fludarabine and Cyclophosphamide With or Without Rituximab Before CD19 Chimeric Antigen Receptor T Cells for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Rituximab and Pembrolizumab With or Without Lenalidomide in Treating Patients With Relapsed Follicular Lymphoma and Diffuse Large B-Cell Lymphoma