Clinical trial NCT02763319: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Diffuse Large B-cell Lymphoma
Keywords: Diffuse Large B-cell Lymphoma
bendamustine
rituximab
combination therapy
CD19 monoclonal antibody
transplant ineligible
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2016-05-05
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 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 outcomes:
measure: Objective response rate (ORR)
timeFrame: From date of randomization assessed up to 4 yrs
measure: Duration of response (DoR)
timeFrame: From date of randomization assessed up to 4 yrs
measure: overall survival (OS)
timeFrame: From date of randomization assessed up to 4 yrs
measure: disease control rate (DCR)
timeFrame: From date of randomization assessed up to 4 yrs
measure: time to progression (TTP)
timeFrame: From date of randomization assessed up to 4 yrs
measure: time to next treatment (TTNT)
timeFrame: From date of randomization assessed up to 4 yrs
measure: Number of patients with adverse events
timeFrame: assessed up to 4 yrs
measure: quality of life (QoL)
timeFrame: assessed up to 4 yrs
measure: Number of patients developing Tafasitamab antibodies
timeFrame: assessed up to 2 yrs
measure: Maximum Plasma Concentration of Tafasitamab (Cmax)
timeFrame: assessed up to 2 yrs
measure: Apparent trough concentration (Cpd) of Tafsitamab
timeFrame: assessed up to 2 yrs
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: MorphoSys Research Site
state: California
city: Bakersfield
country: United States
facility: MorphoSys Research Site
state: California
city: Burbank
country: United States
facility: Morphosys Research Site
state: California
city: Fresno
country: United States
facility: Morphosys Research Site
state: California
city: Los Angeles
country: United States
facility: MorphoSys Research Site
state: California
city: Whittier
country: United States
facility: MorphoSys Research Site
state: California
city: Plainville
country: United States
facility: MorphoSys Research Site
state: Connecticut
city: Skokie
country: United States
facility: MorphoSys Research Site
state: Illinois
city: Detroit
country: United States
facility: MorphoSys Research Site
state: Michigan
city: Rochester
country: United States
facility: MorphoSys Research Site
state: Minnesota
city: Hattiesburg
country: United States
facility: MorphoSys Research Site
state: Mississippi
city: Jackson
country: United States
facility: Morphosys Research site
state: Mississippi
city: Morristown
country: United States
facility: Morphosys Research Site
state: New Jersey
city: New York
country: United States
facility: MorphoSys Research Site
state: New York
city: Stony Brook
country: United States
facility: MorphoSys Research Site
state: New York
city: Oklahoma City
country: United States
facility: MorphoSys Research Site
state: Oklahoma
city: Knoxville
country: United States
facility: MorphoSys Research Site
state: Tennessee
city: Lubbock
country: United States
facility: Morphosys Research Site
state: Texas
city: Adelaide
country: Australia
facility: MorphoSys Research Site
city: Albury
country: Australia
facility: MorphoSys Research Site
city: Bedford Park
country: Australia
facility: MorphoSys Research Site
city: Box Hill
country: Australia
facility: MorphoSys Research Site
city: Concord
country: Australia
facility: MorphoSys Research Site
city: Frankston
country: Australia
facility: MorphoSys Research Site
city: Garran
country: Australia
facility: MorphoSys Research SIte
city: Geelong
country: Australia
facility: MorphoSys Research Site
city: Gosford
country: Australia
facility: MorphoSys Research Site
city: Nedlands
country: Australia
facility: MorphoSys Research Site
city: South Brisbane
country: Australia
facility: MorphoSys Research Site
city: St. Albans
country: Australia
facility: MorphoSys Research Site
city: Innsbruck
country: Austria
facility: MorphoSys Research Site
city: Edmonton
country: Canada
facility: Morphosys Research Site
state: Alberta
city: Winnipeg
country: Canada
facility: MorphoSys Research Site
state: Manitoba
city: Saint John
country: Canada
facility: MorphoSys Research Site
state: New Brunswick
city: Saint John's
country: Canada
facility: Morphosys Research Site
state: Newfoundland and Labrador
city: Kingston
country: Canada
facility: MorphoSys Research Site
state: Ontario
city: Greenfield Park
country: Canada
facility: MorphoSys Research Site
state: Quebec
city: Montréal
country: Canada
facility: Morphosys Research Site
state: Quebec
city: Saskatoon
country: Canada
facility: MorphoSys Research Site
city: Zagreb
country: Croatia
facility: MorphoSys Research Site
city: Hradec Kralove
country: Czechia
facility: MorphoSys Research Site
city: Olomouc
country: Czechia
facility: Morphosys Research site
city: Prague
country: Czechia
facility: Morphosys Research Site
city: Prague
country: Czechia
facility: MorphoSys Research Site
city: Oulu
country: Finland
facility: MorphoSys Research Site
city: Tampere
country: Finland
facility: MorphoSys Research Site
city: Grenoble
country: France
facility: MorphoSys Research Site
city: Le Mans
country: France
facility: MorphoSys Research Site
city: Aachen
country: Germany
facility: MorphoSys Research Site
city: Berlin
country: Germany
facility: MorphoSys Research Site
city: Berlin
country: Germany
facility: MorphoSys Research Site
city: Düsseldorf
country: Germany
facility: MorphoSys Research Site
city: Giessen
country: Germany
facility: MorphoSys Research Site
city: Homburg
country: Germany
facility: Morphosys Research Site
city: Leipzig
country: Germany
facility: MorphoSys Research Site
city: Mainz
country: Germany
facility: MorphoSys Research Site
city: Munich
country: Germany
facility: MorphoSys Research Site
city: Munich
country: Germany
facility: MorphoSys Research Site
city: Mutlangen
country: Germany
facility: MorphoSys Research Site
city: Münster
country: Germany
facility: Morphosys Research Site
city: Rostock
country: Germany
facility: MorphoSys Research Site
city: Stuttgart
country: Germany
facility: MorphoSys Research Site
city: Stuttgart
country: Germany
facility: MorphoSys Research Site
city: Traunstein
country: Germany
facility: MorphoSys
city: Budapest
country: Hungary
facility: MorphoSys
city: Debrecen
country: Hungary
facility: MorphoSys Research Site
city: Győr
country: Hungary
facility: MorphoSys Research Site
city: Szeged
country: Hungary
facility: MorphoSys
city: Haifa
country: Israel
facility: MorphoSys Research Site
city: Jerusalem
country: Israel
facility: MorphoSys Research Site
city: Jerusalem
country: Israel
facility: MorphoSys Research Site
city: Kfar Saba
country: Israel
facility: MorphoSys Research Site
city: Tel Aviv
country: Israel
facility: MorphoSys Research Site
city: Alessandria
country: Italy
facility: MorphoSys Research Site
city: Bologna
country: Italy
facility: MorphoSys Research Site
city: Campobasso
country: Italy
facility: MorphoSys Research Site
city: Cona
country: Italy
facility: MorphoSys Research Site
city: Genova
country: Italy
facility: MorphoSys Research Site
city: Lecce
country: Italy
facility: MorphoSys Research Site
city: Meldola
country: Italy
facility: MorphoSys Research Site
city: Monza
country: Italy
facility: MorphoSys Research Site
city: Napoli
country: Italy
facility: MorphoSys Research Site
city: Novara
country: Italy
facility: Morphosys Research Site
city: Orbassano
country: Italy
facility: MorphoSys Research Site
city: Parma
country: Italy
facility: MorphoSys Research Site
city: Pavia
country: Italy
facility: MorphoSys Research Site
city: Pisa
country: Italy
facility: MorphoSys Research Site
city: Ravenna
country: Italy
facility: MorphoSys Research Site
city: Reggio Emilia
country: Italy
facility: MorphoSys Research Site
city: Rimini
country: Italy
facility: MorphoSys Research Site
city: Rome
country: Italy
facility: MorphoSys Research Site
city: Rome
country: Italy
facility: MorphoSys Research Site
city: Terni
country: Italy
facility: Morphosys Research Site
city: Turin
country: Italy
facility: MorphoSys Research Site
city: Turin
country: Italy
facility: Morphosys Research Site
city: Busan
country: Korea, Republic of
facility: MorphoSys Research Site
city: Goyang-si
country: Korea, Republic of
facility: MorphoSys Research Site
city: Incheon
country: Korea, Republic of
facility: MorphoSys Research Site
city: Jeonju
country: Korea, Republic of
facility: MorphoSys Research Site
city: Seongnam
country: Korea, Republic of
facility: MorphoSys Research Site
city: Seoul
country: Korea, Republic of
facility: MorphoSys Research Site
city: Seoul
country: Korea, Republic of
facility: MorphoSys Research Site
city: Seoul
country: Korea, Republic of
facility: MorphoSys Research Site
city: Seoul
country: Korea, Republic of
facility: MorphoSys Research Site
city: Ulsan
country: Korea, Republic of
facility: MorphoSys Research Site
city: Addington
country: New Zealand
facility: MorphoSys Research Site
city: Auckland
country: New Zealand
facility: MorphoSys Research Site
city: Grafton
country: New Zealand
facility: MorphoSys Research Site
city: Bydgoszcz
country: Poland
facility: Morphosys Research Site
city: Gdynia
country: Poland
facility: MorphoSys Research Site
city: Kraków
country: Poland
facility: MorphoSys Research Site
city: Legnica
country: Poland
facility: MorphoSys Research Site
city: Lodz
country: Poland
facility: MorphoSys Research Site
city: Lublin
country: Poland
facility: MorphoSys Research Site
city: Warszawa
country: Poland
facility: Morphosys Research Site
city: Wrocław
country: Poland
facility: MorphoSys Research Site
city: Braga
country: Portugal
facility: MorphoSys Research Site
city: Coimbra
country: Portugal
facility: MorphoSys Research Site
city: Coimbra
country: Portugal
facility: MorphoSys Research Site
city: Matosinhos
country: Portugal
facility: MorphoSys Research Site
city: Porto
country: Portugal
facility: MorphoSys Research Site
city: Porto
country: Portugal
facility: MorphoSys Research Site
city: Pragal
country: Portugal
facility: MorphoSys Research Site
city: Bucharest
country: Romania
facility: MorphoSys Research Site
city: Bucharest
country: Romania
facility: MorphoSys Research Site
city: Iaşi
country: Romania
facility: MorphoSys Research Site
city: Belgrade
country: Serbia
facility: MorphoSys Research Site
city: Kragujevac
country: Serbia
facility: MorphoSys Research Site
city: Singapore
country: Singapore
facility: MorphoSys Research Site
city: Singapore
country: Singapore
facility: MorphoSys Research Site
city: Singapore
country: Singapore
facility: MorphoSys Research Site
city: Singapore
country: Singapore
facility: MorphoSys Research Site
city: Cadiz
country: Spain
facility: MorphoSys Research Site
city: Girona
country: Spain
facility: MorphoSys Research Site
city: L'Hospitalet De Llobregat
country: Spain
facility: MorphoSys Research Site
city: Madrid
country: Spain
facility: MorphoSys Research Site
city: Madrid
country: Spain
facility: MorphoSys Research Site
city: Madrid
country: Spain
facility: MorphoSys Research Site
city: Palma de Mallorca
country: Spain
facility: MorphoSys Research Site
city: Pamplona
country: Spain
facility: MorphoSys Research Site
city: Pozuelo De Alarcón
country: Spain
facility: MorphoSys Research Site
city: Sabadell
country: Spain
facility: MorphoSys
city: Salamanca
country: Spain
facility: MorphoSys Research Site
city: Valencia
country: Spain
facility: MorphoSys Research Site
city: Chang Hua
country: Taiwan
facility: Morphosys Research Site
city: Hualien City
country: Taiwan
facility: Morphosys Research Site
city: Taichung City
country: Taiwan
facility: Morphosys Research Site
city: Adana
country: Turkey
facility: MorphoSys Research Site
city: Ankara
country: Turkey
facility: MorphoSys Research Site
city: Ankara
country: Turkey
facility: MorphoSys Research Site
city: Bornova
country: Turkey
facility: MorphoSys Research Site
city: Gaziantep
country: Turkey
facility: MorphoSys Research Site
city: İzmir
country: Turkey
facility: MorphoSys Research Site
city: Manisa
country: Turkey
facility: MorphoSys Research Site
city: Samsun
country: Turkey
facility: MorphoSys Research Site
city: Birmingham
country: United Kingdom
facility: Morphosys Research Site
city: Leeds
country: United Kingdom
facility: MorphoSys Research Site
city: Southend on Sea
country: United Kingdom
facility: MorphoSys Research Site
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Director
role: STUDY_DIRECTOR
References: