B-MIND: 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)

Sponsor

MorphoSys AG (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02763319

Collaborator

ICON Clinical Research (Industry)

450

Enrollment

158

Locations

Arms

Duration (Months)

2.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-cell Lymphoma	Drug: Rituximab (RTX) Drug: Tafasitamab Drug: Bendamustine (BEN)	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

450 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

Outcome assessor: blinding on treatment group

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2016

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tafasitamab and bendamustine 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 Rituximab and bendamustine	Drug: Rituximab (RTX) Rituximab: Dose: 375 mg/m2 IV Other Names: Rituxan Mab Thera Drug: Bendamustine (BEN) Other Names: Levact/Treanda

Arm

Intervention/Treatment

Experimental: Tafasitamab and bendamustine

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

Rituximab and bendamustine

Drug: Rituximab (RTX)

Rituximab: Dose: 375 mg/m2 IV

Other Names:

Rituxan

Mab Thera

Drug: Bendamustine (BEN)

Other Names:

Levact/Treanda

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) [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]
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)

Secondary Outcome Measures

Objective response rate (ORR) [From date of randomization assessed up to 4 yrs]
To determine efficacy
Duration of response (DoR) [From date of randomization assessed up to 4 yrs]
To determine efficacy
overall survival (OS) [From date of randomization assessed up to 4 yrs]
To determine efficacy
disease control rate (DCR) [From date of randomization assessed up to 4 yrs]
To determine efficacy
time to progression (TTP) [From date of randomization assessed up to 4 yrs]
To determine efficacy
time to next treatment (TTNT) [From date of randomization assessed up to 4 yrs]
To determine efficacy
Number of patients with adverse events [assessed up to 4 yrs]
Number of participants with treatment- and non-treatment related adverse events as assessed by CTCAE
quality of life (QoL) [assessed up to 4 yrs]
EORTC QLQ-C30 and EQ-5D-5L questionnaires will be used
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

Age ≥18 years
Histologically confirmed diagnosis, according to the World Health Organization (WHO,

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.

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.
Patients must have:
relapsed or refractory DLBCL
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
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.
ECOG 0 to 2
Patients after failure of ASCT or patients considered in the opinion of the investigator currently not eligible for HDC with subsequent ASCT.
Patients must meet the following laboratory criteria at Screening:
ANC ≥1.5 × 109/L (unless secondary to bone marrow involvement by DLBCL)
PLTs ≥90 × 109/L (unless secondary to bone marrow involvement by DLBCL) and absence of active bleeding
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
ALT, AST and AP ≤3 × ULN or <5 × ULN in cases of documented liver involvement by lymphoma
serum creatinine ≤2.0 x ULN or creatinine clearance must be ≥40 mL/min calculated using a standard Cockcroft-Gault formula (Cockroft & Gault, 1976)
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.
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.
In the opinion of the investigator, the patients must:
be able to comply with all study-related procedures, medication use, and evaluations
be able to understand and give informed consent
not be considered to be potentially unreliable and/or not cooperative.

EXCLUSION CRITERIA:

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
Patients who had a major surgery less than 30 days prior to Day 1 dosing
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
received live vaccines
required parenteral antimicrobial therapy for active, intercurrent systemic infections
Patients who:
in the opinion of the investigator, have not recovered sufficiently from the adverse toxic effects of prior therapies, major surgeries or significant traumatic injuries
were previously treated with CD19-targeted therapy or BEN
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
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.
have undergone previous allogeneic stem cell transplantation
concurrently use other anticancer or experimental treatments
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:
basal cell carcinoma of the skin
squamous cell carcinoma of the skin
carcinoma in situ of the cervix, breast and bladder

incidental histological finding of prostate cancer (Tumour/Node/Metastasis [TNM] stage of T1a or T1b)

Patients with:
positive hepatitis B and/or C serology
known seropositivity for or history of active viral infection with HIV
evidence of active, severe uncontrolled systemic infections or sepsis
a history or evidence of severely immunocompromised state
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
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MorphoSys Research Site	Anaheim	California	United States	92801
2	MorphoSys Research Site	Bakersfield	California	United States	93309
3	Morphosys Research Site	Burbank	California	United States	91505
4	Morphosys Research Site	Fresno	California	United States	93701
5	MorphoSys Research Site	Los Angeles	California	United States	90017
6	MorphoSys Research Site	Whittier	California	United States	90603
7	MorphoSys Research Site	Plainville	Connecticut	United States	06062
8	MorphoSys Research Site	Skokie	Illinois	United States	60077
9	MorphoSys Research Site	Detroit	Michigan	United States	48202
10	MorphoSys Research Site	Rochester	Minnesota	United States	55905
11	MorphoSys Research Site	Hattiesburg	Mississippi	United States	39401
12	Morphosys Research site	Jackson	Mississippi	United States	39126
13	Morphosys Research Site	Morristown	New Jersey	United States	07960
14	MorphoSys Research Site	New York	New York	United States	10029
15	MorphoSys Research Site	Stony Brook	New York	United States	11794
16	MorphoSys Research Site	Oklahoma City	Oklahoma	United States	73142-2015
17	MorphoSys Research Site	Knoxville	Tennessee	United States	37909
18	Morphosys Research Site	Lubbock	Texas	United States	79415
19	MorphoSys Research Site	Adelaide		Australia	5000
20	MorphoSys Research Site	Albury		Australia	2640
21	MorphoSys Research Site	Bedford Park		Australia	5042
22	MorphoSys Research Site	Box Hill		Australia	3128
23	MorphoSys Research Site	Concord		Australia	2139
24	MorphoSys Research Site	Frankston		Australia	3199
25	MorphoSys Research SIte	Garran		Australia	2605
26	MorphoSys Research Site	Geelong		Australia	3220
27	MorphoSys Research Site	Gosford		Australia	2250
28	MorphoSys Research Site	Nedlands		Australia	6009
29	MorphoSys Research Site	South Brisbane		Australia	4101
30	MorphoSys Research Site	St. Albans		Australia	3021
31	MorphoSys Research Site	Innsbruck		Austria	6020
32	Morphosys Research Site	Edmonton	Alberta	Canada	T6G 1Z2
33	MorphoSys Research Site	Winnipeg	Manitoba	Canada	R3E 0V9
34	MorphoSys Research Site	Saint John	New Brunswick	Canada	E2L 4L2
35	Morphosys Research Site	Saint John's	Newfoundland and Labrador	Canada	A1B 3V6
36	MorphoSys Research Site	Kingston	Ontario	Canada	K7L 5P9
37	MorphoSys Research Site	Greenfield Park	Quebec	Canada	J4V 2H1
38	Morphosys Research Site	Montréal	Quebec	Canada	H1T 2M4
39	MorphoSys Research Site	Saskatoon		Canada	S7N4H4
40	MorphoSys Research Site	Zagreb		Croatia	10000
41	MorphoSys Research Site	Hradec Kralove		Czechia	50005
42	Morphosys Research site	Olomouc		Czechia	77900
43	Morphosys Research Site	Prague		Czechia	12808
44	MorphoSys Research Site	Prague		Czechia	15006
45	MorphoSys Research Site	Oulu		Finland	90220
46	MorphoSys Research Site	Tampere		Finland	33521
47	MorphoSys Research Site	Grenoble		France	38043
48	MorphoSys Research Site	Le Mans		France	72037
49	MorphoSys Research Site	Aachen		Germany	52074
50	MorphoSys Research Site	Berlin		Germany	10967
51	MorphoSys Research Site	Berlin		Germany	12351
52	MorphoSys Research Site	Düsseldorf		Germany	40479
53	MorphoSys Research Site	Giessen		Germany	35392
54	Morphosys Research Site	Homburg		Germany	66421
55	MorphoSys Research Site	Leipzig		Germany	04103
56	MorphoSys Research Site	Mainz		Germany	55131
57	MorphoSys Research Site	Munich		Germany	81377
58	MorphoSys Research Site	Munich		Germany	81737
59	MorphoSys Research Site	Mutlangen		Germany	73557
60	Morphosys Research Site	Münster		Germany	48149
61	MorphoSys Research Site	Rostock		Germany	18057
62	MorphoSys Research Site	Stuttgart		Germany	70199
63	MorphoSys Research Site	Stuttgart		Germany	70376
64	MorphoSys	Traunstein		Germany	83278
65	MorphoSys	Budapest		Hungary	1083
66	MorphoSys Research Site	Debrecen		Hungary	4032
67	MorphoSys Research Site	Győr		Hungary	9024
68	MorphoSys	Szeged		Hungary	6725
69	MorphoSys Research Site	Haifa		Israel	31096
70	MorphoSys Research Site	Jerusalem		Israel	90131
71	MorphoSys Research Site	Jerusalem		Israel	91120
72	MorphoSys Research Site	Kfar Saba		Israel	44281
73	MorphoSys Research Site	Tel Aviv		Israel	69710
74	MorphoSys Research Site	Alessandria		Italy	15121
75	MorphoSys Research Site	Bologna		Italy	40138
76	MorphoSys Research Site	Campobasso		Italy	86100
77	MorphoSys Research Site	Cona		Italy	44124
78	MorphoSys Research Site	Genova		Italy	16132
79	MorphoSys Research Site	Lecce		Italy	73100
80	MorphoSys Research Site	Meldola		Italy	47014
81	MorphoSys Research Site	Monza		Italy	20900
82	MorphoSys Research Site	Napoli		Italy	80131
83	Morphosys Research Site	Novara		Italy	28100
84	MorphoSys Research Site	Orbassano		Italy	10043
85	MorphoSys Research Site	Parma		Italy	43100
86	MorphoSys Research Site	Pavia		Italy	27100
87	MorphoSys Research Site	Pisa		Italy	56126
88	MorphoSys Research Site	Ravenna		Italy	48121
89	MorphoSys Research Site	Reggio Emilia		Italy	42100
90	MorphoSys Research Site	Rimini		Italy	47923
91	MorphoSys Research Site	Rome		Italy	00128
92	MorphoSys Research Site	Rome		Italy	00144
93	Morphosys Research Site	Terni		Italy	05100
94	MorphoSys Research Site	Turin		Italy	10043
95	Morphosys Research Site	Turin		Italy	10126
96	MorphoSys Research Site	Busan		Korea, Republic of	49201
97	MorphoSys Research Site	Goyang-si		Korea, Republic of	10408
98	MorphoSys Research Site	Incheon		Korea, Republic of	21565
99	MorphoSys Research Site	Jeonju		Korea, Republic of	54907
100	MorphoSys Research Site	Seongnam		Korea, Republic of	13620
101	MorphoSys Research Site	Seoul		Korea, Republic of	03722
102	MorphoSys Research Site	Seoul		Korea, Republic of	05505
103	MorphoSys Research Site	Seoul		Korea, Republic of	07985
104	MorphoSys Research Site	Seoul		Korea, Republic of	135710
105	MorphoSys Research Site	Ulsan		Korea, Republic of	44033
106	MorphoSys Research Site	Addington		New Zealand	8011
107	MorphoSys Research Site	Auckland		New Zealand	2025
108	MorphoSys Research Site	Grafton		New Zealand	1148
109	Morphosys Research Site	Bydgoszcz		Poland	85-796
110	MorphoSys Research Site	Gdynia		Poland	81-519
111	MorphoSys Research Site	Kraków		Poland	30-510
112	MorphoSys Research Site	Legnica		Poland	59-220
113	MorphoSys Research Site	Lodz		Poland	93-510
114	MorphoSys Research Site	Lublin		Poland	20-090
115	Morphosys Research Site	Warszawa		Poland	02781
116	MorphoSys Research Site	Wrocław		Poland	50-556
117	MorphoSys Research Site	Braga		Portugal	4710243
118	MorphoSys Research Site	Coimbra		Portugal	3000-075
119	MorphoSys Research Site	Coimbra		Portugal	3000075
120	MorphoSys Research Site	Matosinhos		Portugal	4464-504
121	MorphoSys Research Site	Porto		Portugal	4099001
122	MorphoSys Research Site	Porto		Portugal	4200072
123	MorphoSys Research Site	Pragal		Portugal	2901-951
124	MorphoSys Research Site	Bucharest		Romania	022328
125	MorphoSys Research Site	Bucharest		Romania	30171
126	MorphoSys Research Site	Iaşi		Romania	700483
127	MorphoSys Research Site	Belgrade		Serbia	11000
128	MorphoSys Research Site	Kragujevac		Serbia	34000
129	MorphoSys Research Site	Singapore		Singapore	119074
130	MorphoSys Research Site	Singapore		Singapore	169610
131	MorphoSys Research Site	Singapore		Singapore	188770
132	MorphoSys Research Site	Singapore		Singapore	258499
133	MorphoSys Research Site	Cadiz		Spain	11009
134	MorphoSys Research Site	Girona		Spain	17007
135	MorphoSys Research Site	L'Hospitalet De Llobregat		Spain	08908
136	MorphoSys Research Site	Madrid		Spain	28007
137	MorphoSys Research Site	Madrid		Spain	28023
138	MorphoSys Research Site	Madrid		Spain	28050
139	MorphoSys Research Site	Palma de Mallorca		Spain	07198
140	MorphoSys Research Site	Pamplona		Spain	31008
141	MorphoSys Research Site	Pozuelo De Alarcón		Spain	28223
142	MorphoSys	Sabadell		Spain	08208
143	MorphoSys Research Site	Salamanca		Spain	37007
144	MorphoSys Research Site	Valencia		Spain	46940
145	Morphosys Research Site	Chang Hua		Taiwan	50006
146	Morphosys Research Site	Hualien City		Taiwan	97002
147	Morphosys Research Site	Taichung City		Taiwan	40447
148	MorphoSys Research Site	Adana		Turkey	01330
149	MorphoSys Research Site	Ankara		Turkey	06500
150	MorphoSys Research Site	Ankara		Turkey	06590
151	MorphoSys Research Site	Bornova		Turkey	35100
152	MorphoSys Research Site	Gaziantep		Turkey	27310
153	MorphoSys Research Site	İzmir		Turkey	35340
154	MorphoSys Research Site	Manisa		Turkey	45010
155	MorphoSys Research Site	Samsun		Turkey	55139
156	Morphosys Research Site	Birmingham		United Kingdom	B71 4HJ
157	MorphoSys Research Site	Leeds		United Kingdom	LS97 TF
158	MorphoSys Research Site	Southend on Sea		United Kingdom	SS0 0RY