A Trial to Evaluate the Efficacy and Safety of Tafasitamab With Bendamustine (BEN) Versus Rituximab (RTX) With BEN in Adult Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Diffuse Large B-cell Lymphoma Clinical Trial

— B-MIND  

Official title:

A Phase 2/3, Randomised, Multicentre Study of Tafasitamab With Bendamustine Versus Rituximab With Bendamustine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL) Who Are Not Eligible for High-Dose Chemotherapy (HDC) and Autologous Stem-Cell Transplantation (ASCT)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02763319
• Other study ID #: MOR208C204
• Secondary ID: 2014-004689-11
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: June 2016
• Est. completion date: June 2024

Study information

• Verified date: August 2022
• Source: MorphoSys AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to compare the safety and efficacy of Tafasitamab with BEN versus RTX with BEN in adult patients with relapsed of refractory DLBCL.

Description:

This is a randomised, two-arm, multicentre, open-label phase II/III efficacy and safety study of Tafasitamab in combination with BEN versus RTX in combination with BEN given to adult patients who have relapsed after or are refractory to at least one but no more than three prior systemic therapies and have failed, or are not candidates for HDC and ASCT, and have thus exhausted their therapeutic options of demonstrated clinical benefit. At least one prior therapy line must have included a CD20-targeted therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 450
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA:

1. Age =18 years

2. Histologically confirmed diagnosis, according to the World Health Organization (WHO, 2008) classification, of: DLBCL NOS, THRLBCL, EBV-positive DLBCL, composite lymphoma with a DLBCL component with a DLBCL relapse subsequent to DLBCL treatment, disease transformed from an earlier diagnosis of low grade lymphoma (i.e. an indolent pathology such as follicular lymphoma, marginal zone lymphoma) into DLBCL with a DLBCL relapse subsequent to DLBCL treatment.

3. Fresh tumour tissue for central pathology review must be provided as an adjunct to participation in this study. Should it not be possible to obtain a fresh tumour tissue sample, archival paraffin embedded tumour tissue acquired =3 years prior to screening for this protocol must be available for this purpose.

4. Patients must have:

1. relapsed or refractory DLBCL

2. at least one bidimensionally measurable disease site. The lesion must have a greatest transverse diameter of =1.5 cm and greatest perpendicular diameter of =1.0 cm at baseline. The lesion must be positive on PET scan

3. received at least one, but no more than three previous systemic therapy lines for the treatment of DLBCL. At least one previous therapy line must have included a CD20-targeted.

4. ECOG 0 to 2

5. Patients after failure of ASCT or patients considered in the opinion of the investigator currently not eligible for HDC with subsequent ASCT.

6. Patients must meet the following laboratory criteria at Screening:

1. ANC =1.5 × 109/L (unless secondary to bone marrow involvement by DLBCL)

2. PLTs =90 × 109/L (unless secondary to bone marrow involvement by DLBCL) and absence of active bleeding

3. total serum bilirubin =2.5 × ULN unless secondary to Gilbert's syndrome (or pattern consistent with Gilbert's) or documented liver involvement by lymphoma. Patients with Gilbert's syndrome or documented liver involvement by lymphoma may be included if their total bilirubin is =5 x ULN

4. ALT, AST and AP =3 × ULN or <5 × ULN in cases of documented liver involvement by lymphoma

5. serum creatinine =2.0 x ULN or creatinine clearance must be =40 mL/min calculated using a standard Cockcroft-Gault formula (Cockroft & Gault, 1976)

7. For a female of childbearing potential (FCBP), a negative pregnancy test must be confirmed before enrolment. An FCBP must commit to take highly effective contraceptive precautions without interruption during the study and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later. An FCBP must refrain from breastfeeding and donating blood or oocytes during the course of the study and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later. Restrictions concerning blood donations apply as well to females who are not of childbearing potential.

8. Males must use an effective barrier method of contraception without interruption during the study and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later, if the patient is sexually active with an FCBP. Males must refrain from donating blood or sperm during study participation and for 3, 6 or 12 months after the last dose of Tafasitamab, BEN or RTX respectively, whichever is later.

9. In the opinion of the investigator, the patients must:

1. be able to comply with all study-related procedures, medication use, and evaluations

2. be able to understand and give informed consent

3. not be considered to be potentially unreliable and/or not cooperative.

EXCLUSION CRITERIA:

1. Patients who have: any other histological type of lymphoma including, e.g., primary mediastinal (thymic) large B-cell lymphoma (PMBL) or Burkitt's lymphoma, primary refractory DLBCL, patients with known "double/triple hit" DLBCL genetics, CNS lymphoma involvement in present or past medical history

2. Patients who had a major surgery less than 30 days prior to Day 1 dosing

3. Patients who have, within 14 days prior to Day 1 dosing:

1. not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma-specific therapy

2. received live vaccines

3. required parenteral antimicrobial therapy for active, intercurrent systemic infections

4. Patients who:

1. in the opinion of the investigator, have not recovered sufficiently from the adverse toxic effects of prior therapies, major surgeries or significant traumatic injuries

2. were previously treated with CD19-targeted therapy or BEN

3. have a history of previous severe allergic reactions to compounds of similar biological or chemical composition to Tafasitamab, RTX, murine proteins or BEN, or the excipients contained in the study drug formulations

4. have undergone ASCT within a period of =3 months prior to signing the informed consent form. Patients who have a more distant history of ASCT must exhibit full haematological recovery before enrolment into the study.

5. have undergone previous allogeneic stem cell transplantation

6. concurrently use other anticancer or experimental treatments

5. Prior history of malignancies other than DLBCL, unless the patient has been free of the disease for =3 years prior to Screening. Exceptions to the =3-year time limit

include history of the following:

1. basal cell carcinoma of the skin

2. squamous cell carcinoma of the skin

3. carcinoma in situ of the cervix, breast and bladder f) incidental histological finding of prostate cancer (Tumour/Node/Metastasis [TNM] stage of T1a or T1b)

6. Patients with:

1. positive hepatitis B and/or C serology

2. known seropositivity for or history of active viral infection with HIV

3. evidence of active, severe uncontrolled systemic infections or sepsis

4. a history or evidence of severely immunocompromised state

5. a history or evidence of severe hepatic impairment (total serum bilirubin > 3 mg/dL), jaundice unless secondary to Gilbert's syndrome or documented liver involvement by lymphoma

6. a history or evidence of clinically significant cardiovascular, cerebrovascular, CNS and/or other disease that, in the investigator's opinion, would preclude participation in the study or compromise the patient's ability to give informed consent

Related Conditions & MeSH terms

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

Intervention

Drug:
• Rituximab (RTX)
Rituximab: Dose: 375 mg/m2 IV
• Tafasitamab
Tafasitamab: Tafasitamab dose: 12 mg/kg intravenously (IV)
• Bendamustine (BEN)

Locations

Country	Name	City	State
Australia	MorphoSys Research Site	Adelaide
Australia	MorphoSys Research Site	Albury
Australia	MorphoSys Research Site	Bedford Park
Australia	MorphoSys Research Site	Box Hill
Australia	MorphoSys Research Site	Concord
Australia	MorphoSys Research Site	Frankston
Australia	MorphoSys Research SIte	Garran
Australia	MorphoSys Research Site	Geelong
Australia	MorphoSys Research Site	Gosford
Australia	MorphoSys Research Site	Nedlands
Australia	MorphoSys Research Site	South Brisbane
Australia	MorphoSys Research Site	St. Albans
Austria	MorphoSys Research Site	Innsbruck
Canada	Morphosys Research Site	Edmonton	Alberta
Canada	MorphoSys Research Site	Greenfield Park	Quebec
Canada	MorphoSys Research Site	Kingston	Ontario
Canada	Morphosys Research Site	Montréal	Quebec
Canada	MorphoSys Research Site	Saint John	New Brunswick
Canada	Morphosys Research Site	Saint John's	Newfoundland and Labrador
Canada	MorphoSys Research Site	Saskatoon
Canada	MorphoSys Research Site	Winnipeg	Manitoba
Croatia	MorphoSys Research Site	Zagreb
Czechia	MorphoSys Research Site	Hradec Kralove
Czechia	Morphosys Research site	Olomouc
Czechia	Morphosys Research Site	Prague
Czechia	MorphoSys Research Site	Prague
Finland	MorphoSys Research Site	Oulu
Finland	MorphoSys Research Site	Tampere
France	MorphoSys Research Site	Grenoble
France	MorphoSys Research Site	Le Mans
Germany	MorphoSys Research Site	Aachen
Germany	MorphoSys Research Site	Berlin
Germany	MorphoSys Research Site	Berlin
Germany	MorphoSys Research Site	Düsseldorf
Germany	MorphoSys Research Site	Giessen
Germany	Morphosys Research Site	Homburg
Germany	MorphoSys Research Site	Leipzig
Germany	MorphoSys Research Site	Mainz
Germany	MorphoSys Research Site	Munich
Germany	MorphoSys Research Site	Munich
Germany	Morphosys Research Site	Münster
Germany	MorphoSys Research Site	Mutlangen
Germany	MorphoSys Research Site	Rostock
Germany	MorphoSys Research Site	Stuttgart
Germany	MorphoSys Research Site	Stuttgart
Germany	MorphoSys	Traunstein
Hungary	MorphoSys	Budapest
Hungary	MorphoSys Research Site	Debrecen
Hungary	MorphoSys Research Site	Gyor
Hungary	MorphoSys	Szeged
Israel	MorphoSys Research Site	Haifa
Israel	MorphoSys Research Site	Jerusalem
Israel	MorphoSys Research Site	Jerusalem
Israel	MorphoSys Research Site	Kfar Saba
Israel	MorphoSys Research Site	Tel Aviv
Italy	MorphoSys Research Site	Alessandria
Italy	MorphoSys Research Site	Bologna
Italy	MorphoSys Research Site	Campobasso
Italy	MorphoSys Research Site	Cona
Italy	MorphoSys Research Site	Genova
Italy	MorphoSys Research Site	Lecce
Italy	MorphoSys Research Site	Meldola
Italy	MorphoSys Research Site	Monza
Italy	MorphoSys Research Site	Napoli
Italy	Morphosys Research Site	Novara
Italy	MorphoSys Research Site	Orbassano
Italy	MorphoSys Research Site	Parma
Italy	MorphoSys Research Site	Pavia
Italy	MorphoSys Research Site	Pisa
Italy	MorphoSys Research Site	Ravenna
Italy	MorphoSys Research Site	Reggio Emilia
Italy	MorphoSys Research Site	Rimini
Italy	MorphoSys Research Site	Rome
Italy	MorphoSys Research Site	Rome
Italy	Morphosys Research Site	Terni
Italy	MorphoSys Research Site	Turin
Italy	Morphosys Research Site	Turin
Korea, Republic of	MorphoSys Research Site	Busan
Korea, Republic of	MorphoSys Research Site	Goyang-si
Korea, Republic of	MorphoSys Research Site	Incheon
Korea, Republic of	MorphoSys Research Site	Jeonju
Korea, Republic of	MorphoSys Research Site	Seongnam
Korea, Republic of	MorphoSys Research Site	Seoul
Korea, Republic of	MorphoSys Research Site	Seoul
Korea, Republic of	MorphoSys Research Site	Seoul
Korea, Republic of	MorphoSys Research Site	Seoul
Korea, Republic of	MorphoSys Research Site	Ulsan
New Zealand	MorphoSys Research Site	Addington
New Zealand	MorphoSys Research Site	Auckland
New Zealand	MorphoSys Research Site	Grafton
Poland	Morphosys Research Site	Bydgoszcz
Poland	MorphoSys Research Site	Gdynia
Poland	MorphoSys Research Site	Kraków
Poland	MorphoSys Research Site	Legnica
Poland	MorphoSys Research Site	Lodz
Poland	MorphoSys Research Site	Lublin
Poland	Morphosys Research Site	Warszawa
Poland	MorphoSys Research Site	Wroclaw
Portugal	MorphoSys Research Site	Braga
Portugal	MorphoSys Research Site	Coimbra
Portugal	MorphoSys Research Site	Coimbra
Portugal	MorphoSys Research Site	Matosinhos
Portugal	MorphoSys Research Site	Porto
Portugal	MorphoSys Research Site	Porto
Portugal	MorphoSys Research Site	Pragal
Romania	MorphoSys Research Site	Bucharest
Romania	MorphoSys Research Site	Bucharest
Romania	MorphoSys Research Site	Iasi
Serbia	MorphoSys Research Site	Belgrade
Serbia	MorphoSys Research Site	Kragujevac
Singapore	MorphoSys Research Site	Singapore
Singapore	MorphoSys Research Site	Singapore
Singapore	MorphoSys Research Site	Singapore
Singapore	MorphoSys Research Site	Singapore
Spain	MorphoSys Research Site	Cadiz
Spain	MorphoSys Research Site	Girona
Spain	MorphoSys Research Site	L'Hospitalet De Llobregat
Spain	MorphoSys Research Site	Madrid
Spain	MorphoSys Research Site	Madrid
Spain	MorphoSys Research Site	Madrid
Spain	MorphoSys Research Site	Palma de Mallorca
Spain	MorphoSys Research Site	Pamplona
Spain	MorphoSys Research Site	Pozuelo De Alarcón
Spain	MorphoSys	Sabadell
Spain	MorphoSys Research Site	Salamanca
Spain	MorphoSys Research Site	Valencia
Taiwan	Morphosys Research Site	Chang Hua
Taiwan	Morphosys Research Site	Hualien City
Taiwan	Morphosys Research Site	Taichung City
Turkey	MorphoSys Research Site	Adana
Turkey	MorphoSys Research Site	Ankara
Turkey	MorphoSys Research Site	Ankara
Turkey	MorphoSys Research Site	Bornova
Turkey	MorphoSys Research Site	Gaziantep
Turkey	MorphoSys Research Site	Izmir
Turkey	MorphoSys Research Site	Manisa
Turkey	MorphoSys Research Site	Samsun
United Kingdom	Morphosys Research Site	Birmingham
United Kingdom	MorphoSys Research Site	Leeds
United Kingdom	MorphoSys Research Site	Southend on Sea
United States	MorphoSys Research Site	Anaheim	California
United States	MorphoSys Research Site	Bakersfield	California
United States	Morphosys Research Site	Burbank	California
United States	MorphoSys Research Site	Detroit	Michigan
United States	Morphosys Research Site	Fresno	California
United States	MorphoSys Research Site	Hattiesburg	Mississippi
United States	Morphosys Research site	Jackson	Mississippi
United States	MorphoSys Research Site	Knoxville	Tennessee
United States	MorphoSys Research Site	Los Angeles	California
United States	Morphosys Research Site	Lubbock	Texas
United States	Morphosys Research Site	Morristown	New Jersey
United States	MorphoSys Research Site	New York	New York
United States	MorphoSys Research Site	Oklahoma City	Oklahoma
United States	MorphoSys Research Site	Plainville	Connecticut
United States	MorphoSys Research Site	Rochester	Minnesota
United States	MorphoSys Research Site	Skokie	Illinois
United States	MorphoSys Research Site	Stony Brook	New York
United States	MorphoSys Research Site	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
MorphoSys AG	ICON Clinical Research

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Croatia,  Czechia,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  New Zealand,  Poland,  Portugal,  Romania,  Serbia,  Singapore,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	To determine the efficacy of a combination of MOR00208 with BEN versus a combination of RTX with BEN in terms of progression-free survival (PFS) in: Adult patients with R-R DLBCL (overall population); A subgroup of adult patients with R-R DLBCL with low baseline peripheral blood NK-cell count (NKCC-low)	From date of randomization until recurrence/disease progression, unacceptable toxicity, death or discontinuation for any other reason, whichever comes first assessed up to 4 yrs
Secondary	Objective response rate (ORR)	To determine efficacy	From date of randomization assessed up to 4 yrs
Secondary	Duration of response (DoR)	To determine efficacy	From date of randomization assessed up to 4 yrs
Secondary	overall survival (OS)	To determine efficacy	From date of randomization assessed up to 4 yrs
Secondary	disease control rate (DCR)	To determine efficacy	From date of randomization assessed up to 4 yrs
Secondary	time to progression (TTP)	To determine efficacy	From date of randomization assessed up to 4 yrs
Secondary	time to next treatment (TTNT)	To determine efficacy	From date of randomization assessed up to 4 yrs
Secondary	Number of patients with adverse events	Number of participants with treatment- and non-treatment related adverse events as assessed by CTCAE	assessed up to 4 yrs
Secondary	quality of life (QoL)	EORTC QLQ-C30 and EQ-5D-5L questionnaires will be used	assessed up to 4 yrs
Secondary	Number of patients developing Tafasitamab antibodies		assessed up to 2 yrs
Secondary	Maximum Plasma Concentration of Tafasitamab (Cmax)		assessed up to 2 yrs
Secondary	Apparent trough concentration (Cpd) of Tafsitamab		assessed up to 2 yrs