Study Stopped
PI left institution and funding sponsor closed study. Study did not open to accrual, and no participants were enrolled.
Loncastuximab Tesirine in Combination With Chemotherapy Prior to Stem Cell Transplant for the Treatment of Recurrent or Refractory Diffuse Large B-Cell Lymphoma
3 other identifiers
interventional
N/A
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Apr 2023
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 27, 2022
CompletedFirst Posted
Study publicly available on registry
February 8, 2022
CompletedStudy Start
First participant enrolled
April 1, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2027
ExpectedJanuary 13, 2023
January 1, 2023
2.5 years
January 27, 2022
January 11, 2023
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of dose-limiting toxicity (Part 1)
Will be descriptive based on the appropriate analysis set and may include summary statistics such as means/median, standard deviations, range for continuous variables, and count/percentage for categorical variables, if applicable.
Up to 30 days
Incidence of toxicity requiring dose delay or modification (Part 2)
Will be descriptive based on the appropriate analysis set and may include summary statistics such as means/median, standard deviations, range for continuous variables, and count/percentage for categorical variables, if applicable.
Up to 30 days
Secondary Outcomes (2)
Progression-free survival
Time from receiving loncastuximab tesirine to the first observation of disease progression or death from any cause, whichever occurs first, assessed at 2 years post-autologous stem cell transplantation (ASCT)
Overall survival
Time from receiving loncastuximab tesirine to death from any cause, assessed at 2 years post-ASCT
Study Arms (1)
Treatment (loncastuximab tesirine, BEAM chemotherapy)
EXPERIMENTALPART I (CONDITIONING): Patients receive loncastuximab tesirine IV on day -7, carmustine IV over 2 hours on day -7, etoposide IV over 1-2 hours 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 Q3V for up to 9 cycles in the absence of disease progression or unacceptable toxicity.
Interventions
Undergo peripheral blood ASCT
Given IV
Given IV
Given IV
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- 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
- PART 1: Women of childbearing potential (WOCBP), defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year, must have a negative serum pregnancy test within 7 days of and prior to initiating loncastuximab tesirine in combination with BEAM conditioning
- Fertile male and WOCBP subjects must be willing to use highly effective contraceptive methods before, during, and for at least 6 months after ASCT or 9 months after the last administration of loncastuximab tesirine for women, 6 months after the last administration of loncastuximab tesirine for men, whichever is longer
- PART 1: Ability to provide informed consent
- PART 2: Eligible disease status. Following ASCT (within day +30 to +90), subjects must have achieved radiographic partial response (PR) or complete response (CR) via PET/CT and/or diagnostic CT
- PART 2: Targeted radiation therapy following ASCT is allowed but must be completed \>= 2 weeks prior to starting maintenance therapy
- +6 more criteria
You may not qualify if:
- 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: 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
- PART 1: Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on bone marrow biopsy prior to initiation of therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- ADC Therapeuticscollaborator
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Victor Chow
Fred Hutch/University of Washington Cancer Consortium
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 27, 2022
First Posted
February 8, 2022
Study Start
April 1, 2023
Primary Completion
October 1, 2025
Study Completion (Estimated)
October 1, 2027
Last Updated
January 13, 2023
Record last verified: 2023-01
Data Sharing
- IPD Sharing
- Will not share