Clinical trial NCT05222555: Safety and Pharmacokinetics Study of a Modified Tafasitamab IV Dosing Regimen Combined With Lenalidomide in R-R DLBCL Patients
Official title: A Phase 1b/2, Open-Label, Multicenter Study to Evaluate the Safety and Pharmacokinetics of a Modified Tafasitamab IV Dosing Regimen Combined With Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B Cell Lymphoma
Keywords: monoclonal antibody
CD19
tafasitamab
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2022-02-03
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Major Inclusion Criteria:

1. Capable of giving signed informed consent
2. Age 18 years or older
3. Histologically confirmed diagnosis of DLBCL
4. Tumor tissue for retrospective central pathology review must be provided as an adjunct to participation in this study.
5. 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
6. Patients not considered in the opinion of the investigator eligible to undergo intensive salvage therapy including ASCT
7. 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
8. 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
9. Patients with primary refractory disease who received at least one, but no more than three previous systemic regimens (including a CD20 targeted therapy)

Major Exclusion Criteria:

1. Patients who are legally institutionalized or concurrent enrollment in another interventional clinical study
2. Patients who have:

   * other histological type of lymphoma
   * a history of "double/triple hit" genetics
3. 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
4. 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
5. 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
6. 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
7. 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

Primary outcomes:
measure: Evaluate safety and tolerability
timeFrame: 1 - 3 years approximately
measure: Determine recommended dose
timeFrame: 1 - 3 years approximately
Secondary outcomes:
measure: Evaluate pharmacokinetic profile
timeFrame: Upto 1 year
measure: Evaluate pharmacokinetic profile
timeFrame: Upto 3 months
measure: Assess anti-tumor activity
timeFrame: upto 1 year
measure: Duration of response (DoR)
timeFrame: 1 - 3 years approximatey
measure: Progression-free Survival (PFS)
timeFrame: 1 - 3 years approximately
Other outcomes:
measure: B cell numbers
timeFrame: upto 1 year
measure: T cell numbers
timeFrame: upto 1 year
measure: NK cell numbers
timeFrame: upto 1 year
Locations:
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center - USOR
state: Texas
city: Olympia
country: United States
facility: Vista Oncology
state: Washington
city: Sankt Pölten
country: Austria
facility: UK St. Pölten
state: Niederösterreich
city: Wels
country: Austria
facility: Klinikum Wels Grieskirchen
state: Oberösterreich
city: Salzburg
country: Austria
facility: Universitatsklinikum Salzburg
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha
country: Czechia
facility: Vseobecna Fakultni Nemocnice V Praze
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon
state: Isère
city: Nantes
country: France
facility: CHU Nantes
state: Loire-Atlantique
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
state: Sarthe
city: Poitiers
country: France
facility: CHU de Poitiers
state: Vienne
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Centre
state: HaDarom
city: Be'er Ya'aqov
country: Israel
facility: Shamir Medical Center Assaf Harofeh
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center - Hadassah Ein Kerem
city: Zefat
country: Israel
facility: ZIV Medical Center
city: Ravenna
country: Italy
facility: Ospedale Santa Maria Delle Croci
state: Emilia-Romagna
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo di Pavia
state: Lombardia
city: Monza
country: Italy
facility: ASST di Monza - Azienda Ospedaliera San Gerardo
state: Monza E Brianza
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia (IRCCS)
state: Piemonte
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia
state: Umbria
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
state: Gyeonggido
city: Busan
country: Korea, Republic of
facility: Dong-A University Medical Center
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Busan
country: Korea, Republic of
facility: Kosin University Gospel Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Hospital
city: Daegu
country: Korea, Republic of
facility: Daegu Catholic University Medical Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Jeonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - PPDS
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Yeouido St. Mary's Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
state: Dolnoslaskie
city: Wrocław
country: Poland
facility: Dolnoslaskie Centrum Onkologii, Pulmonologii i Hematologii
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Pratia MCM Krakow
state: Malopolskie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
state: Mazowieckie
city: Opole
country: Poland
facility: Szpital Wojewodzki w Opolu
state: Opolskie
city: Skórzewo
country: Poland
facility: Centrum Medyczne Poznan - PRATIA - PPDS
state: Wielkopolskie
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o. o.
city: Krakow
country: Poland
facility: SP ZOZ Szpital Uniwersytecki w Krakowie
city: Olsztyn
country: Poland
facility: SPZOZ MiSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
city: Torun
country: Poland
facility: Nasz Lekarz Osrodek Badan Klinicznych
city: Łódź
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
state: Baleares
city: Girona
country: Spain
facility: Institut Catala d'Oncologia Girona
city: L´Hospitalet de Llobregat
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital U. Infanta Leonor
city: Madrid
country: Spain
facility: MD Anderson Madrid
city: Madrid
country: Spain
facility: Hospital U. Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital U. Quironsalud Madrid
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - H. Clinico
city: Sevilla
country: Spain
facility: Hospital U. Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari La Fe
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Director
role: STUDY_DIRECTOR
References: