Safety and Pharmacokinetics Study of a Modified Tafasitamab IV Dosing Regimen Combined With Lenalidomide in R-R DLBCL Patients
- Conditions
- Diffuse Large B Cell Lymphoma
- Interventions
- Registration Number
- NCT05222555
- Lead Sponsor
- Incyte Corporation
- Brief Summary
This is an open-label, multicentre study too Evaluate the Safety and Pharmacokinetics of a Modified Tafasitamab IV Dosing Regimen Combined with Lenalidomide (LEN) in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL) who have had at least one, but no more than three prior systemic regimens and who are not eligible for high dose chemotherapy (HDC) with autologous stem-cell transplantation (ASCT) at the time of study entry.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 53
-
Capable of giving signed informed consent
-
Age 18 years or older
-
Histologically confirmed diagnosis of DLBCL
-
Tumor tissue for retrospective central pathology review must be provided as an adjunct to participation in this study.
-
Patients must have:
- relapsed and/or refractory disease
- at least one bidimensionally measurable, PET positive disease site (transverse diameter of ≥1.5 cm and perpendicular diameter of ≥1.0 cm at baseline)
- received at least one, but no more than three previous systemic regimens for the treatment of DLBCL and one therapy line must have included a CD20-targeted therapy
- Eastern Cooperative Oncology Group 0 to 2
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Patients not considered in the opinion of the investigator eligible to undergo intensive salvage therapy including ASCT
-
Patients must meet the following laboratory criteria at screening:
- absolute neutrophil count ≥1.5 × 10^9/L
- platelet count ≥90 × 10^9/L
- total serum bilirubin ≤2.5 × ULN or ≤5 × ULN in cases of Glibert's Syndrome or liver involvement by lymphoma
- alanine transaminase, aspartate aminotransferase and alkaline phosphatase ≤3 × ULN or <5 × ULN in cases of liver involvement
- serum creatinine clearance ≥ 60 mL/minute
-
Patients who received previous CD19 targeted therapy (other than tafasitamab) must have CD19 positive lymphoma confirmed on a biopsy taken since completing the prior CD19 targeted therapy
-
Patients with primary refractory disease who received at least one, but no more than three previous systemic regimens (including a CD20 targeted therapy)
Major
-
Patients who are legally institutionalized or concurrent enrollment in another interventional clinical study
-
Patients who have:
- other histological type of lymphoma
- a history of "double/triple hit" genetics
-
Patients who have, within 14 days prior to Day 1 dosing:
- not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy
- undergone major surgery (with 4 weeks) or suffered from significant traumatic injury
- received live vaccines (within 4 weeks).
- required parenteral antimicrobial therapy for active, intercurrent infections
-
Patients who:
- have not recovered sufficiently from the adverse toxic effects of prior therapies
- were previously treated with IMiDs® (e.g. thalidomide, LEN)
- have history of hyper sensitivity to compounds of similar biological or chemical composition to tafasitamab IMiDs® and/or the excipients contained in the study treatment formulations
- have undergone ASCT within the period ≤ 3 months prior to signing the informed consent form.
- have undergone previous allogenic stem cell transplantation
- have a history of deep venous thrombosis/embolism and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period
- concurrently use other anticancer or experimental treatments
-
History of other malignancy that could affect compliance with the protocol or interpretation of results. Exceptions
- Patients with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for >2 years prior to enrollment are eligible
- Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible
-
Patients with:
- positive hepatitis B and/or C serology.
- known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV)
- CNS lymphoma involvement
- history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator's opinion preclude participation in the study or compromise the patient's ability to give informed consent
- history or evidence of rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
- gastrointestinal (GI) abnormalities (issue with absorption) including the inability to take oral medication
- history or evidence of severe hepatic impairment (total serum bilirubin > 3mg/dL), jaundice unless secondary to Gilbert's syndrome or documented liver involvement by lymphoma
- history of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical class
- any other medical condition which, in the investigator's opinion, makes the patient unsuitable for the study
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Female participants: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and refrain from breast feeding and donating eggs; agreement to ongoing pregnancy testing during the course of the study, and after study therapy has ended Male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom and agreement to refrain from donating sperm
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (Tafasitamab + Lenalidomide) Tafasitamab Treatment: Tafasitamab will be combined with lenalidomide in R/R DLBCL patients. Dose: Cohort 1: The dose of tafasitamab will be level 1 high dose in combination with the approved dose Cohort 2: The dose of tafasitamab will be level 2 high dose in combination with the approved dose Expansion Cohort: The dose of tafasitamab will be the dose that is deemed safe and tolerable as determined from cohort 1 \& cohort 2 Treatment consisting of tafasitamab and lenalidomide combination will be administered until disease progression, unacceptable toxicity, or discontinuation for any other reason, whichever comes first. Lenalidomide can be given for up to 12 cycles in total, after which patients can continue with tafasitamab as monotherapy until progression or unacceptable toxicity. Treatment (Tafasitamab + Lenalidomide) Lenalidomide Treatment: Tafasitamab will be combined with lenalidomide in R/R DLBCL patients. Dose: Cohort 1: The dose of tafasitamab will be level 1 high dose in combination with the approved dose Cohort 2: The dose of tafasitamab will be level 2 high dose in combination with the approved dose Expansion Cohort: The dose of tafasitamab will be the dose that is deemed safe and tolerable as determined from cohort 1 \& cohort 2 Treatment consisting of tafasitamab and lenalidomide combination will be administered until disease progression, unacceptable toxicity, or discontinuation for any other reason, whichever comes first. Lenalidomide can be given for up to 12 cycles in total, after which patients can continue with tafasitamab as monotherapy until progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Evaluate safety and tolerability 1 - 3 years approximately Incidence and severity of TEAEs
Determine recommended dose 1 - 3 years approximately Incidence and severity of TEAEs combination with lenalidomide in R/R DLBCL patients
- Secondary Outcome Measures
Name Time Method Evaluate pharmacokinetic profile Upto 3 months Tafasitamab serum concentration (Cmax)
Progression-free Survival (PFS) 1 - 3 years approximately Investigator assessment
Assess anti-tumor activity upto 1 year Number of participants with Best Objective Response Rate, ORR = complete response \[CR\] + partial response \[PR\]; by Investigator assessment based on Cheson et al (2007)
Duration of response (DoR) 1 - 3 years approximatey Investigator assessment
Trial Locations
- Locations (62)
Vseobecna Fakultni Nemocnice V Praze
🇨🇿Praha, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha, Czechia
Texas Oncology-Baylor Charles A. Sammons Cancer Center - USOR
🇺🇸Dallas, Texas, United States
Fondazione IRCCS Policlinico San Matteo di Pavia
🇮🇹Pavia, Lombardia, Italy
Hospital Son Llatzer
🇪🇸Palma de Mallorca, Baleares, Spain
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Toscana, Italy
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Azienda Ospedaliera di Perugia
🇮🇹Perugia, Umbria, Italy
CHU Nantes
🇫🇷Nantes, Loire-Atlantique, France
ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda
🇮🇹Milano, Lombardia, Italy
Fondazione del Piemonte per l'Oncologia (IRCCS)
🇮🇹Candiolo, Piemonte, Italy
Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Lombardia, Italy
ASST di Monza - Azienda Ospedaliera San Gerardo
🇮🇹Monza, Monza E Brianza, Italy
Daegu Catholic University Medical Center
🇰🇷Daegu, Korea, Republic of
Asan Medical Center - PPDS
🇰🇷Seoul, Korea, Republic of
Complejo Asistencial Universitario de Salamanca - H. Clinico
🇪🇸Salamanca, Spain
Hospital U. Ramon y Cajal
🇪🇸Madrid, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
🇪🇸L´Hospitalet de Llobregat, Spain
Hospital U. Infanta Leonor
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital U. Quironsalud Madrid
🇪🇸Madrid, Spain
The Catholic University of Korea, St. Vincent's Hospital
🇰🇷Suwon-si, Gyeonggido, Korea, Republic of
Dong-A University Medical Center
🇰🇷Busan, Korea, Republic of
Kosin University Gospel Hospital
🇰🇷Busan, Korea, Republic of
Yeungnam University Hospital
🇰🇷Daegu, Korea, Republic of
Chonbuk National University Hospital
🇰🇷Jeonju, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Hanyang University Medical Center
🇰🇷Seoul, Korea, Republic of
MD Anderson Madrid
🇪🇸Madrid, Spain
Institut Catala d'Oncologia Girona
🇪🇸Girona, Spain
Hospital U. Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitari La Fe
🇪🇸Valencia, Spain
Vista Oncology
🇺🇸Olympia, Washington, United States
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Czechia
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Soroka University Medical Centre
🇮🇱Be'er Sheva, HaDarom, Israel
ZIV Medical Center
🇮🇱Zefat, Israel
Shamir Medical Center Assaf Harofeh
🇮🇱Be'er Ya'aqov, Israel
Ospedale Santa Maria Delle Croci
🇮🇹Ravenna, Emilia-Romagna, Italy
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
The Catholic University of Korea, Yeouido St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
🇵🇱Warszawa, Mazowieckie, Poland
Klinikum Wels Grieskirchen
🇦🇹Wels, Oberösterreich, Austria
Universitatsklinikum Salzburg
🇦🇹Salzburg, Austria
Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon
🇫🇷Grenoble, Isère, France
UK St. Pölten
🇦🇹Sankt Pölten, Niederösterreich, Austria
SP ZOZ Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
Centre Hospitalier Le Mans
🇫🇷Le Mans, Sarthe, France
Hadassah Medical Center - Hadassah Ein Kerem
🇮🇱Jerusalem, Israel
CHU de Poitiers
🇫🇷Poitiers, Vienne, France
SPZOZ MiSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
🇵🇱Olsztyn, Poland
Morristown Memorial Hospital
🇺🇸Morristown, New Jersey, United States
Centrum Medyczne Poznan - PRATIA - PPDS
🇵🇱Skórzewo, Wielkopolskie, Poland
Nasz Lekarz Osrodek Badan Klinicznych
🇵🇱Torun, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
🇵🇱Wroclaw, Dolnoslaskie, Poland
Dolnoslaskie Centrum Onkologii, Pulmonologii i Hematologii
🇵🇱Wrocław, Dolnoslaskie, Poland
Szpital Wojewodzki w Opolu
🇵🇱Opole, Opolskie, Poland
Pratia MCM Krakow
🇵🇱Krakow, Malopolskie, Poland
Szpitale Pomorskie Sp. z o. o.
🇵🇱Gdynia, Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
🇵🇱Łódź, Poland