Safety and Pharmacokinetics Study of a Modified Tafasitamab IV Dosing Regimen Combined With Lenalidomide in R-R DLBCL Patients

Diffuse Large B Cell Lymphoma Clinical Trial

— MINDway  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05222555
• Other study ID #: MOR208C115
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 19, 2022
• Est. completion date: October 31, 2027

Study information

• Verified date: May 2024
• Source: MorphoSys AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 53
• Est. completion date: October 31, 2027
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Tafasitamab
tafasitamab will be administered intravenously at protocol defined timepoints
• Lenalidomide
lenalidomide will be administered orally at protocol defined timepoints

Locations

Country	Name	City	State
Austria	Universitatsklinikum Salzburg	Salzburg
Austria	UK St. Pölten	Sankt Pölten	Niederösterreich
Austria	Klinikum Wels Grieskirchen	Wels	Oberösterreich
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Ostrava	Ostrava
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha
Czechia	Fakultni nemocnice v Motole	Praha
Czechia	Vseobecna Fakultni Nemocnice V Praze	Praha
France	Centre Hospitalier Universitaire Grenoble Alpes - Hopital Albert Michallon	Grenoble	Isère
France	Centre Hospitalier Le Mans	Le Mans	Sarthe
France	CHU Nantes	Nantes	Loire-Atlantique
France	CHU de Poitiers	Poitiers	Vienne
Israel	Soroka University Medical Centre	Be'er Sheva	HaDarom
Israel	Shamir Medical Center Assaf Harofeh	Be'er Ya'aqov
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Hadassah Medical Center - Hadassah Ein Kerem	Jerusalem
Israel	ZIV Medical Center	Zefat
Italy	Fondazione del Piemonte per l'Oncologia (IRCCS)	Candiolo	Piemonte
Italy	ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda	Milano	Lombardia
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano	Lombardia
Italy	ASST di Monza - Azienda Ospedaliera San Gerardo	Monza	Monza E Brianza
Italy	Fondazione IRCCS Policlinico San Matteo di Pavia	Pavia	Lombardia
Italy	Azienda Ospedaliera di Perugia	Perugia	Umbria
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana
Italy	Ospedale Santa Maria Delle Croci	Ravenna	Emilia-Romagna
Korea, Republic of	Dong-A University Medical Center	Busan
Korea, Republic of	Kosin University Gospel Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Daegu Catholic University Medical Center	Daegu
Korea, Republic of	Yeungnam University Hospital	Daegu
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Chonbuk National University Hospital	Jeonju
Korea, Republic of	Asan Medical Center - PPDS	Seoul
Korea, Republic of	Hanyang University Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea, Yeouido St. Mary's Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si	Gyeonggido
Korea, Republic of	Ulsan University Hospital	Ulsan
Poland	Szpitale Pomorskie Sp. z o. o.	Gdynia
Poland	Pratia MCM Krakow	Krakow	Malopolskie
Poland	SP ZOZ Szpital Uniwersytecki w Krakowie	Krakow
Poland	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lódz
Poland	SPZOZ MiSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn
Poland	Szpital Wojewodzki w Opolu	Opole	Opolskie
Poland	Centrum Medyczne Poznan - PRATIA - PPDS	Skórzewo	Wielkopolskie
Poland	Nasz Lekarz Osrodek Badan Klinicznych	Torun
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa	Mazowieckie
Poland	Dolnoslaskie Centrum Onkologii, Pulmonologii i Hematologii	Wroclaw	Dolnoslaskie
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu	Wroclaw	Dolnoslaskie
Spain	Institut Catala d'Oncologia Girona	Girona
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	L´Hospitalet de Llobregat
Spain	Hospital U. Infanta Leonor	Madrid
Spain	Hospital U. Quironsalud Madrid	Madrid
Spain	Hospital U. Ramon y Cajal	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	MD Anderson Madrid	Madrid
Spain	Hospital Son Llatzer	Palma de Mallorca	Baleares
Spain	Complejo Asistencial Universitario de Salamanca - H. Clinico	Salamanca
Spain	Hospital U. Virgen del Rocio	Sevilla
Spain	Hospital Universitari La Fe	Valencia
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center - USOR	Dallas	Texas
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Vista Oncology	Olympia	Washington

Sponsors (1)

Lead Sponsor	Collaborator
MorphoSys AG

Countries where clinical trial is conducted

United States,  Austria,  Czechia,  France,  Israel,  Italy,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	B cell numbers	Absolute counts and percentage change from baseline in measurement of B cell numbers in peripheral blood	upto 1 year
Other	T cell numbers	Absolute counts and percentage change from baseline in measurement of T cell numbers in peripheral blood	upto 1 year
Other	NK cell numbers	Absolute counts and percentage change from baseline in measurement of NK cell numbers in peripheral blood	upto 1 year
Primary	Evaluate safety and tolerability	Incidence and severity of TEAEs	1 - 3 years approximately
Primary	Determine recommended dose	Incidence and severity of TEAEs combination with lenalidomide in R/R DLBCL patients	1 - 3 years approximately
Secondary	Evaluate pharmacokinetic profile	Tafasitamab serum concentration (Ctrough)	Upto 1 year
Secondary	Evaluate pharmacokinetic profile	Tafasitamab serum concentration (Cmax)	Upto 3 months
Secondary	Assess anti-tumor activity	Number of participants with Best Objective Response Rate, ORR = complete response [CR] + partial response [PR]; by Investigator assessment based on Cheson et al (2007)	upto 1 year
Secondary	Duration of response (DoR)	Investigator assessment	1 - 3 years approximatey
Secondary	Progression-free Survival (PFS)	Investigator assessment	1 - 3 years approximately