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) (B-MIND)

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Tafasitamab; Drug: Bendamustine (BEN); Drug: Rituximab (RTX)

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.

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • MorphoSys Research Site
  • Albury, Australia, 2640
    • MorphoSys Research Site
  • Bedford Park, Australia, 5042
    • MorphoSys Research Site
  • Box Hill, Australia, 3128
    • MorphoSys Research Site
  • Concord, Australia, 2139
    • MorphoSys Research Site
  • Frankston, Australia, 3199
    • MorphoSys Research Site
  • Garran, Australia, 2605
    • MorphoSys Research Site
  • Geelong, Australia, 3220
    • MorphoSys Research Site
  • Gosford, Australia, 2250
    • MorphoSys Research Site
  • Nedlands, Australia, 6009
    • MorphoSys Research Site
  • South Brisbane, Australia, 4101
    • MorphoSys Research Site
  • St. Albans, Australia, 3021
    • MorphoSys Research Site
• Austria
  • Innsbruck, Austria, 6020
    • MorphoSys Research Site
• Canada
  • Saskatoon, Canada, S7N4H4
    • MorphoSys Research Site
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • MorphoSys Research Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • MorphoSys Research Site
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • MorphoSys Research Site
  • Newfoundland and Labrador
    • Saint John's, Newfoundland and Labrador, Canada, A1B 3V6
      • MorphoSys Research Site
  • Ontario
    • Kingston, Ontario, Canada, K7L 5P9
      • MorphoSys Research Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • MorphoSys Research Site
    • Montréal, Quebec, Canada, H1T 2M4
      • MorphoSys Research Site
• Croatia
  • Zagreb, Croatia, 10000
    • MorphoSys Research Site
• Czechia
  • Hradec Kralove, Czechia, 50005
    • MorphoSys Research Site
  • Olomouc, Czechia, 77900
    • MorphoSys Research Site
  • Prague, Czechia, 12808
    • MorphoSys Research Site
  • Prague, Czechia, 15006
    • MorphoSys Research Site
• Finland
  • Oulu, Finland, 90220
    • MorphoSys Research Site
  • Tampere, Finland, 33521
    • MorphoSys Research Site
• France
  • Grenoble, France, 38043
    • MorphoSys Research Site
  • Le Mans, France, 72037
    • MorphoSys Research Site
• Germany
  • Aachen, Germany, 52074
    • MorphoSys Research Site
  • Berlin, Germany, 10967
    • MorphoSys Research Site
  • Berlin, Germany, 12351
    • MorphoSys Research Site
  • Düsseldorf, Germany, 40479
    • MorphoSys Research Site
  • Giessen, Germany, 35392
    • MorphoSys Research Site
  • Homburg, Germany, 66421
    • MorphoSys Research Site
  • Leipzig, Germany, 04103
    • MorphoSys Research Site
  • Mainz, Germany, 55131
    • MorphoSys Research Site
  • Munich, Germany, 81377
    • MorphoSys Research Site
  • Munich, Germany, 81737
    • MorphoSys Research Site
  • Mutlangen, Germany, 73557
    • MorphoSys Research Site
  • Münster, Germany, 48149
    • MorphoSys Research Site
  • Rostock, Germany, 18057
    • MorphoSys Research Site
  • Stuttgart, Germany, 70199
    • MorphoSys Research Site
  • Stuttgart, Germany, 70376
    • MorphoSys Research Site
  • Traunstein, Germany, 83278
    • Morphosys
• Hungary
  • Budapest, Hungary, 1083
    • Morphosys
  • Debrecen, Hungary, 4032
    • MorphoSys Research Site
  • Győr, Hungary, 9024
    • MorphoSys Research Site
  • Szeged, Hungary, 6725
    • Morphosys
• Israel
  • Haifa, Israel, 31096
    • MorphoSys Research Site
  • Jerusalem, Israel, 90131
    • MorphoSys Research Site
  • Jerusalem, Israel, 91120
    • MorphoSys Research Site
  • Kfar Saba, Israel, 44281
    • MorphoSys Research Site
  • Tel Aviv, Israel, 69710
    • MorphoSys Research Site
• Italy
  • Alessandria, Italy, 15121
    • MorphoSys Research Site
  • Bologna, Italy, 40138
    • MorphoSys Research Site
  • Campobasso, Italy, 86100
    • MorphoSys Research Site
  • Cona, Italy, 44124
    • MorphoSys Research Site
  • Genova, Italy, 16132
    • MorphoSys Research Site
  • Lecce, Italy, 73100
    • MorphoSys Research Site
  • Meldola, Italy, 47014
    • MorphoSys Research Site
  • Monza, Italy, 20900
    • MorphoSys Research Site
  • Napoli, Italy, 80131
    • MorphoSys Research Site
  • Novara, Italy, 28100
    • MorphoSys Research Site
  • Orbassano, Italy, 10043
    • MorphoSys Research Site
  • Parma, Italy, 43100
    • MorphoSys Research Site
  • Pavia, Italy, 27100
    • MorphoSys Research Site
  • Pisa, Italy, 56126
    • MorphoSys Research Site
  • Ravenna, Italy, 48121
    • MorphoSys Research Site
  • Reggio Emilia, Italy, 42100
    • MorphoSys Research Site
  • Rimini, Italy, 47923
    • MorphoSys Research Site
  • Rome, Italy, 00128
    • MorphoSys Research Site
  • Rome, Italy, 00144
    • MorphoSys Research Site
  • Terni, Italy, 05100
    • MorphoSys Research Site
  • Turin, Italy, 10043
    • MorphoSys Research Site
  • Turin, Italy, 10126
    • MorphoSys Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49201
    • MorphoSys Research Site
  • Goyang-si, Korea, Republic of, 10408
    • MorphoSys Research Site
  • Incheon, Korea, Republic of, 21565
    • MorphoSys Research Site
  • Jeonju, Korea, Republic of, 54907
    • MorphoSys Research Site
  • Seongnam, Korea, Republic of, 13620
    • MorphoSys Research Site
  • Seoul, Korea, Republic of, 03722
    • MorphoSys Research Site
  • Seoul, Korea, Republic of, 05505
    • MorphoSys Research Site
  • Seoul, Korea, Republic of, 07985
    • MorphoSys Research Site
  • Seoul, Korea, Republic of, 135710
    • MorphoSys Research Site
  • Ulsan, Korea, Republic of, 44033
    • MorphoSys Research Site
• New Zealand
  • Addington, New Zealand, 8011
    • MorphoSys Research Site
  • Auckland, New Zealand, 2025
    • MorphoSys Research Site
  • Grafton, New Zealand, 1148
    • MorphoSys Research Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • MorphoSys Research Site
  • Gdynia, Poland, 81-519
    • MorphoSys Research Site
  • Kraków, Poland, 30-510
    • MorphoSys Research Site
  • Legnica, Poland, 59-220
    • MorphoSys Research Site
  • Lodz, Poland, 93-510
    • MorphoSys Research Site
  • Lublin, Poland, 20-090
    • MorphoSys Research Site
  • Warszawa, Poland, 02781
    • MorphoSys Research Site
  • Wrocław, Poland, 50-556
    • MorphoSys Research Site
• Portugal
  • Braga, Portugal, 4710243
    • MorphoSys Research Site
  • Coimbra, Portugal, 3000-075
    • MorphoSys Research Site
  • Coimbra, Portugal, 3000075
    • MorphoSys Research Site
  • Matosinhos, Portugal, 4464-504
    • MorphoSys Research Site
  • Porto, Portugal, 4099001
    • MorphoSys Research Site
  • Porto, Portugal, 4200072
    • MorphoSys Research Site
  • Pragal, Portugal, 2901-951
    • MorphoSys Research Site
• Romania
  • Bucharest, Romania, 022328
    • MorphoSys Research Site
  • Bucharest, Romania, 30171
    • MorphoSys Research Site
  • Iaşi, Romania, 700483
    • MorphoSys Research Site
• Serbia
  • Belgrade, Serbia, 11000
    • MorphoSys Research Site
  • Kragujevac, Serbia, 34000
    • MorphoSys Research Site
• Singapore
  • Singapore, Singapore, 119074
    • MorphoSys Research Site
  • Singapore, Singapore, 169610
    • MorphoSys Research Site
  • Singapore, Singapore, 188770
    • MorphoSys Research Site
  • Singapore, Singapore, 258499
    • MorphoSys Research Site
• Spain
  • Cadiz, Spain, 11009
    • MorphoSys Research Site
  • Girona, Spain, 17007
    • MorphoSys Research Site
  • L'Hospitalet De Llobregat, Spain, 08908
    • MorphoSys Research Site
  • Madrid, Spain, 28007
    • MorphoSys Research Site
  • Madrid, Spain, 28023
    • MorphoSys Research Site
  • Madrid, Spain, 28050
    • MorphoSys Research Site
  • Palma de Mallorca, Spain, 07198
    • MorphoSys Research Site
  • Pamplona, Spain, 31008
    • MorphoSys Research Site
  • Pozuelo De Alarcón, Spain, 28223
    • MorphoSys Research Site
  • Sabadell, Spain, 08208
    • Morphosys
  • Salamanca, Spain, 37007
    • MorphoSys Research Site
  • Valencia, Spain, 46940
    • MorphoSys Research Site
• Taiwan
  • Chang Hua, Taiwan, 50006
    • MorphoSys Research Site
  • Hualien City, Taiwan, 97002
    • MorphoSys Research Site
  • Taichung City, Taiwan, 40447
    • MorphoSys Research Site
• Turkey
  • Adana, Turkey, 01330
    • MorphoSys Research Site
  • Ankara, Turkey, 06500
    • MorphoSys Research Site
  • Ankara, Turkey, 06590
    • MorphoSys Research Site
  • Bornova, Turkey, 35100
    • MorphoSys Research Site
  • Gaziantep, Turkey, 27310
    • MorphoSys Research Site
  • Manisa, Turkey, 45010
    • MorphoSys Research Site
  • Samsun, Turkey, 55139
    • MorphoSys Research Site
  • İzmir, Turkey, 35340
    • MorphoSys Research Site
• United Kingdom
  • Birmingham, United Kingdom, B71 4HJ
    • MorphoSys Research Site
  • Leeds, United Kingdom, LS97 TF
    • MorphoSys Research Site
  • Southend on Sea, United Kingdom, SS0 0RY
    • MorphoSys Research Site
• United States
  • California
    • Anaheim, California, United States, 92801
      • MorphoSys Research Site
    • Bakersfield, California, United States, 93309
      • MorphoSys Research Site
    • Burbank, California, United States, 91505
      • MorphoSys Research Site
    • Fresno, California, United States, 93701
      • MorphoSys Research Site
    • Los Angeles, California, United States, 90017
      • MorphoSys Research Site
    • Whittier, California, United States, 90603
      • MorphoSys Research Site
  • Connecticut
    • Plainville, Connecticut, United States, 06062
      • MorphoSys Research Site
  • Illinois
    • Skokie, Illinois, United States, 60077
      • MorphoSys Research Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • MorphoSys Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • MorphoSys Research Site
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • MorphoSys Research Site
    • Jackson, Mississippi, United States, 39126
      • MorphoSys Research Site
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • MorphoSys Research Site
  • New York
    • New York, New York, United States, 10029
      • MorphoSys Research Site
    • Stony Brook, New York, United States, 11794
      • MorphoSys Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73142-2015
      • MorphoSys Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • MorphoSys Research Site
  • Texas
    • Lubbock, Texas, United States, 79415
      • MorphoSys Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tafasitamab and bendamustine	Drug: Tafasitamab; Tafasitamab: Tafasitamab dose: 12 mg/kg intravenously (IV); Drug: Bendamustine (BEN); Other Names: Levact/Treanda
Active Comparator: Rituximab and bendamustine	Drug: Bendamustine (BEN); Other Names: Levact/Treanda; Drug: Rituximab (RTX); Rituximab: Dose: 375 mg/m2 IV; Other Names: Rituxan; Mab Thera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	To determine efficacy	From date of randomization assessed up to 4 yrs
Duration of response (DoR)	To determine efficacy	From date of randomization assessed up to 4 yrs
overall survival (OS)	To determine efficacy	From date of randomization assessed up to 4 yrs
disease control rate (DCR)	To determine efficacy	From date of randomization assessed up to 4 yrs
time to progression (TTP)	To determine efficacy	From date of randomization assessed up to 4 yrs
time to next treatment (TTNT)	To determine efficacy	From date of randomization assessed up to 4 yrs
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
quality of life (QoL)	EORTC QLQ-C30 and EQ-5D-5L questionnaires will be used	assessed up to 4 yrs
Number of patients developing Tafasitamab antibodies		assessed up to 2 yrs
Maximum Plasma Concentration of Tafasitamab (Cmax)		assessed up to 2 yrs
Apparent trough concentration (Cpd) of Tafsitamab		assessed up to 2 yrs

Collaborators and Investigators

• Sponsor: MorphoSys AG
• Collaborators: ICON Clinical Research

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: April 30, 2016
• First Submitted That Met QC Criteria: May 3, 2016
• First Posted (Estimate): May 5, 2016

Study Record Updates

• Last Update Posted (Actual): August 2, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: rituximab; combination therapy; Diffuse Large B-cell Lymphoma; bendamustine; CD19 monoclonal antibody; transplant ineligible
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Bendamustine Hydrochloride; Rituximab
• Other Study ID Numbers: MOR208C204; 2014-004689-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No