A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL
Study Details
Study Description
Brief Summary
This study is evaluating the efficacy of acalabrutinib in combination with bendamustine and rituximab (BR) compared with placebo plus BR in subjects with previously untreated mantle cell lymphoma.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Detailed Description
To evaluate the efficacy of acalabrutinib in combination with bendamustine and rituximab (BR) compared with placebo plus BR based on Independent Review Committee (IRC) assessment of progression-free survival (PFS) per the Lugano Classification for Non-Hodgkin Lymphoma (NHL) in subjects with previously untreated mantle cell lymphoma (MCL).
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Acalabrutinib in combination with bendamustine and rituximab Acalabrutinib administered twice per day (BID) orally (PO) plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days. |
Drug: Acalabrutinib
Administered orally (PO)
Other Names:
Drug: Bendamustine
Administered intravenously (IV)
Other Names:
Drug: Rituximab
Administered intravenously (IV)
Other Names:
|
Placebo Comparator: Placebo in combination with bendamustine and rituximab Matching placebo administered BID PO plus bendamustine on Days 1 and 2 and rituximab on Day 1; cycles are repeated every 28 days. |
Drug: Bendamustine
Administered intravenously (IV)
Other Names:
Drug: Rituximab
Administered intravenously (IV)
Other Names:
Drug: Placebo
Placebo comparator
|
Outcome Measures
Primary Outcome Measures
- Progression-free survival per the Lugano Classification for NHL in Arm 1 compared to Arm 2 [Up to 6 years]
Defined as the time from the date of randomization until disease progression (assessed by the IRC per the Lugano Classification for NHL) or death from any cause, whichever occurs first.
Secondary Outcome Measures
- Investigator-assessed progression-free survival per the Lugano Classification for NHL in Arm 1 compared to Arm 2 [Up to 6 years]
Defined as the time from the date of randomization until disease progression (assessed by the investigator per the Lugano Classification for NHL) or death from any cause, whichever occurs first.
- Investigator-assessed overall response rate per the Lugano Classification for NHL in Arm 1 compared to Arm 2 [Up to 6 years]
Defined as the proportion of subjects who achieve either partial response (PR) or complete response (CR) as best overall response according to the Lugano Classification for NHL as assessed by investigator.
- IRC-assessed overall response rate per the Lugano Classification for NHL in Arm 1 compared to Arm 2 [Up to 6 years]
Defined as the proportion of subjects who achieve either PR or CR as best overall response according to the Lugano Classification for NHL as assessed by IRC.
- Overall survival in Arm 1 compared to Arm 2 [Up to 6 years]
Defined as the time from randomization until the date of death from any cause.
- IRC-assessed duration of response per the Lugano Classification for NHL in Arm 1 compared to Arm 2 [Up to 6 years]
Defined as the time from the first documentation of CR or PR to disease progression per the Lugano Classification for NHL or death from any cause, whichever occurs first.
- IRC assessed time to response per the Lugano Classification for NHL in Arm 1 compared to Arm 2 [Up to 6 years]
Defined as the time from randomization to the first CR or PR per the Lugano Classification for NHL.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Men and women, ≥ 65 years of age.
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Pathologically confirmed MCL, with documentation of a chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers (eg, CD5, CD19, CD20, PAX5) .
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MCL requiring treatment and for which no prior systemic anticancer therapies have been received.
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Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
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Agreement to use highly effective forms of contraception during the study and 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longest .
Exclusion Criteria:
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Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of first dose of study drug, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval (QTc) > 480 msec (calculated using Friderica's formula: QT/RR0.33) at screening. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.
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Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
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Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti infective treatment within 2 weeks before first dose of study drug.
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Concurrent participation in another therapeutic clinical trial.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Research Site | Downey | California | United States | 90241 |
2 | Research Site | Santa Monica | California | United States | 90404 |
3 | Research Site | New Haven | Connecticut | United States | 06510 |
4 | Research Site | Washington | District of Columbia | United States | 20007 |
5 | Research Site | Tallahassee | Florida | United States | 32308-5304 |
6 | Research Site | West Palm Beach | Florida | United States | 33401 |
7 | Research Site | Marietta | Georgia | United States | 30060 |
8 | Research Site | Westwood | Kansas | United States | 66205 |
9 | Research Site | Louisville | Kentucky | United States | 40207 |
10 | Research Site | Ann Arbor | Michigan | United States | 48109 |
11 | Research Site | Rochester | Minnesota | United States | 55905-0001 |
12 | Research Site | Kansas City | Missouri | United States | 64132 |
13 | Research Site | Saint Louis | Missouri | United States | 63110 |
14 | Research Site | Hackensack | New Jersey | United States | 07601 |
15 | Research Site | Morristown | New Jersey | United States | 07960 |
16 | Research Site | Hawthorne | New York | United States | 10532 |
17 | Research Site | Lake Success | New York | United States | 11042 |
18 | Research Site | Portland | Oregon | United States | 97239 |
19 | Research Site | Charleston | South Carolina | United States | 29425 |
20 | Research Site | Greenville | South Carolina | United States | 29615 |
21 | Research Site | Chattanooga | Tennessee | United States | 37404 |
22 | Research Site | Nashville | Tennessee | United States | 37203 |
23 | Research Site | Houston | Texas | United States | 77030 |
24 | Research Site | San Antonio | Texas | United States | 78217 |
25 | Research Site | San Antonio | Texas | United States | 78217 |
26 | Research Site | Tyler | Texas | United States | 75702 |
27 | Research Site | Charlottesville | Virginia | United States | 22908 |
28 | Research Site | Fort Belvoir | Virginia | United States | 22060 |
29 | Research Site | Seattle | Washington | United States | 98108 |
30 | Research Site | Seattle | Washington | United States | 98109 |
31 | Research Site | Seattle | Washington | United States | 98122 |
32 | Research Site | Morgantown | West Virginia | United States | 26506 |
33 | Research Site | Buenos Aires | Argentina | C1114AAP | |
34 | Research Site | Buenos Aires | Argentina | C1426ANZ | |
35 | Research Site | Buenos Aires | Argentina | C1430EGF | |
36 | Research Site | Buenos Aires | Argentina | C1431FWO | |
37 | Research Site | Caba | Argentina | C1118AAT | |
38 | Research Site | Cordoba | Argentina | 5000 | |
39 | Research Site | Bedford Park | Australia | 5042 | |
40 | Research Site | Concord | Australia | 2139 | |
41 | Research Site | Frankston | Australia | 3199 | |
42 | Research Site | Gosford | Australia | 2250 | |
43 | Research Site | Heidelberg | Australia | 3084 | |
44 | Research Site | Herston | Australia | QLD, 4029 | |
45 | Research Site | Kogarah | Australia | NSW 2217 | |
46 | Research Site | Murdoch | Australia | 6150 | |
47 | Research Site | Nedlands | Australia | 6009 | |
48 | Research Site | Newcastle | Australia | 2298 | |
49 | Research Site | Southport | Australia | 4215 | |
50 | Research Site | Sydney | Australia | NSW 2145 | |
51 | Research Site | Woolloongabba | Australia | 4102 | |
52 | Research Site | Antwerpen | Belgium | 2060 | |
53 | Research Site | Ghent | Belgium | 9000 | |
54 | Research Site | Leuven | Belgium | 3000 | |
55 | Research Site | Roeselare | Belgium | 8900 | |
56 | Research Site | Sint-Niklaas | Belgium | 9100 | |
57 | Research Site | Bela Vista | Brazil | 01321-001 | |
58 | Research Site | Curitiba | Brazil | 81520-060 | |
59 | Research Site | Porto Alegre | Brazil | 90035-903 | |
60 | Research Site | Porto Alegre | Brazil | RS 90610-000 | |
61 | Research Site | Salvador | Brazil | 41253-190 | |
62 | Research Site | Sao Paulo | Brazil | 01232-010 | |
63 | Research Site | Sao Paulo | Brazil | 05652-9000 | |
64 | Research Site | Sao Paulo | Brazil | 1236030 | |
65 | Research Site | Sao Paulo | Brazil | 5403 | |
66 | Research Site | So Paulo | Brazil | 08270-070 | |
67 | Research Site | Vancouver | British Columbia | Canada | V5Z 4E6 |
68 | Research Site | Oshawa | Ontario | Canada | L1G 2B9, |
69 | Research Site | Toronto | Ontario | Canada | M4N 3M5 |
70 | Research Site | Edmonton | Canada | T6G 1Z2 | |
71 | Research Site | Greenfield Park | Canada | J4V 2H1 | |
72 | Research Site | Halifax | Canada | NS B3H 2Y9 | |
73 | Research Site | Beijing | China | 100034 CN | |
74 | Research Site | Beijing | China | 100036 | |
75 | Research Site | Changchun | China | 130021 | |
76 | Research Site | Changsha | China | 410008 | |
77 | Research Site | Chongqing | China | 400037 | |
78 | Research Site | Dalian | China | 116023 | |
79 | Research Site | Fuzhou City | China | 350001 | |
80 | Research Site | Gongshu District | China | 310022 | |
81 | Research Site | Guangzhou | China | 510080 | |
82 | Research Site | Guangzhou | China | ||
83 | Research Site | Haidian District | China | 100191 | |
84 | Research Site | Haikou | China | 570311 | |
85 | Research Site | Hangzhou | China | 310003 | |
86 | Research Site | Harbin | China | 150081 | |
87 | Research Site | Lanzhou | China | 730030 | |
88 | Research Site | Nanchang | China | 330006 | |
89 | Research Site | Nanchang | China | 330029 | |
90 | Research Site | Nanjing | China | 210029 | |
91 | Research Site | Qingdao | China | 266100 | |
92 | Research Site | Shanghai | China | ||
93 | Research Site | Shenyang | China | ||
94 | Research Site | Suzhou | China | 215006 | |
95 | Research Site | Tianjian | China | 300020 | |
96 | Research Site | Tianjin | China | ||
97 | Research Site | Wenzhou | China | 325000 | |
98 | Research Site | Wuhan | China | 430030 | |
99 | Research Site | Wuhan | China | 430079 | |
100 | Research Site | Wuhou District | China | 610041 | |
101 | Research Site | Xicheng District | China | 100050 | |
102 | Research Site | Xuhui District | China | 200032 | |
103 | Research Site | Xuzhou | China | 221000 | |
104 | Research Site | Zhengzhou City | China | 450000 | |
105 | Research Site | Zhengzhou | China | 450008 | |
106 | Research Site | Brno | Czechia | 625 00 | |
107 | Research Site | Hradec Kralove | Czechia | 500 05, CZ | |
108 | Research Site | Ostrava Poruba | Czechia | 708 52 | |
109 | Research Site | Pilsen | Czechia | 30460, CZ | |
110 | Research Site | Prague | Czechia | 100 34, CZ | |
111 | Research Site | Argenteuil | France | 95100 | |
112 | Research Site | Bobigny | France | 93000 | |
113 | Research Site | Bordeaux | France | 33076, FR | |
114 | Research Site | Le Mans | France | 72000, FR | |
115 | Research Site | Limoges | France | 87042 | |
116 | Research Site | Perigueux | France | 24019 | |
117 | Research Site | Pessac | France | 33604 | |
118 | Research Site | Rennes Cedex | France | 35000 | |
119 | Research Site | Vienne | France | 86000, FR | |
120 | Research Site | Heidelberg | Germany | 69120, DE | |
121 | Research Site | Muenster | Germany | 48149 | |
122 | Research Site | Munchen | Germany | 81377, DE | |
123 | Research Site | Nordrhein-Westfalen | Germany | 52064, DE | |
124 | Research Site | Ravensburg | Germany | 88212 | |
125 | Research Site | Rheinland-Pfalz | Germany | 55131, DE | |
126 | Research Site | Ulm | Germany | 89081 | |
127 | Research Site | Athens | Greece | 11525 | |
128 | Research Site | Athens | Greece | 11527, GR | |
129 | Research Site | Athens | Greece | 11528, GR | |
130 | Research Site | Ioannina | Greece | 45500, GR | |
131 | Research Site | Patras | Greece | 26504 | |
132 | Research Site | Thessaloniki | Greece | 54007, GR | |
133 | Research Site | Thessaloniki | Greece | 57010, GR | |
134 | Research Site | HKG | Hong Kong | 999077 | |
135 | Research Site | Pok Fu Lam | Hong Kong | ||
136 | Research Site | Budapest | Hungary | 1085 | |
137 | Research Site | Budapest | Hungary | 1122 | |
138 | Research Site | Debrecen | Hungary | 4032 | |
139 | Research Site | Győr | Hungary | 9024 | |
140 | Research Site | Pecs | Hungary | 7624 | |
141 | Research Site | Szeged | Hungary | 6725 | |
142 | Research Site | Haifa | Israel | 31096 | |
143 | Research Site | Jerusalem | Israel | 9103102 | |
144 | Research Site | Petah Tikva | Israel | 494142 | |
145 | Research Site | Tel Aviv | Israel | 64239 | |
146 | Research Site | Bologna | Italy | 40138 | |
147 | Research Site | Milano | Italy | 20132 | |
148 | Research Site | Milano | Italy | 20162 | |
149 | Research Site | Palermo | Italy | 90146 | |
150 | Research Site | Parma | Italy | ||
151 | Research Site | Pavia | Italy | 27100 | |
152 | Research Site | Reggio Emilia | Italy | 42123 | |
153 | Research Site | Rozzano | Italy | 20089 | |
154 | Research Site | Turin | Italy | 10126 | |
155 | Research Site | Fukuoka City | Japan | 812-8582 | |
156 | Research Site | Fukuoka | Japan | 811-1395 | |
157 | Research Site | Kobe-shi | Japan | 650-0047 | |
158 | Research Site | Kumamoto | Japan | 860-8556 | |
159 | Research Site | Kyoto-city | Japan | 602-8026 | |
160 | Research Site | Matsuyama-shi | Japan | 791-0280 | |
161 | Research Site | Nagoya-shi | Japan | 464-8681 | |
162 | Research Site | Nagoya | Japan | 460-0001 | |
163 | Research Site | Okayama | Japan | 700-8558 | |
164 | Research Site | Osaka | Japan | 565-0871 | |
165 | Research Site | Sapporo-shi | Japan | 003-0006 | |
166 | Research Site | Sendai-shi | Japan | 980-8574 | |
167 | Research Site | Shimane | Japan | 693-8501 | |
168 | Research Site | Tokyo | Japan | 104-0045 | |
169 | Research Site | Tokyo | Japan | 135-8550 | |
170 | Research Site | Tokyo | Japan | 152-8902 | |
171 | Research Site | Yokohama-shi | Japan | 241-8515 | |
172 | Research Site | Busan | Korea, Republic of | 49201 | |
173 | Research Site | Gyeonggi-do | Korea, Republic of | 13620 | |
174 | Research Site | Seoul | Korea, Republic of | 3080 | |
175 | Research Site | Seoul | Korea, Republic of | 3722 | |
176 | Research Site | Seoul | Korea, Republic of | 5505 | |
177 | Research Site | Seoul | Korea, Republic of | 6351 | |
178 | Research Site | Seoul | Korea, Republic of | 6591 | |
179 | Research Site | Mexico | Mexico | 14080 | |
180 | Research Site | Queretaro | Mexico | 76090 | |
181 | Research Site | Dunedin | New Zealand | 9016 | |
182 | Research Site | Grafton | New Zealand | 1023 | |
183 | Research Site | Otahuhu | New Zealand | 1640 | |
184 | Research Site | Bellavista | Peru | ||
185 | Research Site | Lima | Peru | 1 | |
186 | Research Site | Lima | Peru | 34 | |
187 | Research Site | Chorzow | Poland | 41-500 | |
188 | Research Site | Krakow | Poland | 30-510 | |
189 | Research Site | Lodz | Poland | 93-510 | |
190 | Research Site | Lublin | Poland | 20-090 | |
191 | Research Site | Olsztyn | Poland | 10-228 | |
192 | Research Site | Warszawa | Poland | 02-106 | |
193 | Research Site | Warszawa | Poland | 02-776 | |
194 | Research Site | Warszawa | Poland | 04-141 | |
195 | Research Site | Woj. Podkarpackie | Poland | 36-200 | |
196 | Research Site | Wroclaw | Poland | 50-367 | |
197 | Research Site | Brasov | Romania | 50012 | |
198 | Research Site | Bucharest | Romania | 070131 | |
199 | Research Site | Cluj-Napoca | Romania | 400124 | |
200 | Research Site | Iasi | Romania | 700483 | |
201 | Research Site | Pyatigorsk | Russian Federation | 357532 | |
202 | Research Site | Saint Petersburg | Russian Federation | 197022 | |
203 | Research Site | St. Petersburg | Russian Federation | 197341 | |
204 | Research Site | St. Petersburg | Russian Federation | ||
205 | Research Site | Syktyvkar | Russian Federation | 167029 | |
206 | Research Site | Tula | Russian Federation | 300053 | |
207 | Research Site | Badalona | Spain | 8916 | |
208 | Research Site | Barcelona | Spain | 8003 | |
209 | Research Site | Barcelona | Spain | 8035 | |
210 | Research Site | Barcelona | Spain | 8907 | |
211 | Research Site | Barcelona | Spain | ||
212 | Research Site | Madrid | Spain | 28007 | |
213 | Research Site | Madrid | Spain | 28040 | |
214 | Research Site | Madrid | Spain | 28046 | |
215 | Research Site | Majadahonda | Spain | 28222 | |
216 | Research Site | Pamplona | Spain | 31008 | |
217 | Research Site | Sevilla | Spain | ||
218 | Research Site | Valencia | Spain | 46026 | |
219 | Research Site | Kaohsiung | Taiwan | 833 | |
220 | Research Site | Taichung | Taiwan | 40447 | |
221 | Research Site | Taipei | Taiwan | 100 | |
222 | Research Site | Cherkasy | Ukraine | 18009 | |
223 | Research Site | Chernihiv | Ukraine | 14029 | |
224 | Research Site | Dnipropetrovsk | Ukraine | 49102 | |
225 | Research Site | Kiev | Ukraine | 3022 | |
226 | Research Site | Lviv | Ukraine | 79044 | |
227 | Research Site | Zhytomir | Ukraine | 10002 | |
228 | Research Site | Hanoi | Vietnam | 123 | |
229 | Research Site | Hanoi | Vietnam | ||
230 | Research Site | Ho Chi Minh City | Vietnam | WARD 7 | |
231 | Research Site | Ho Chi Minh | Vietnam | 700000 |
Sponsors and Collaborators
- Acerta Pharma BV
- AstraZeneca
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ACE-LY-308