PMID- 33683501
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20220202
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 39
IP  - 4
DP  - 2021 Aug
TI  - A phase Ib, open label, dose escalation trial of the anti-CD37 monoclonal 
      antibody, BI 836826, in combination with ibrutinib in patients with 
      relapsed/refractory chronic lymphocytic leukemia.
PG  - 1099-1105
LID - 10.1007/s10637-020-01056-4 [doi]
AB  - BI 836826 is a chimeric immunoglobulin G1 antibody targeting CD37, a 
      transmembrane protein expressed on normal and malignant B cells. This open-label, 
      phase Ib, dose-escalation study was conducted to determine the recommended phase 
      II dose (RP2D) of BI 836826 + ibrutinib in patients with relapsed/refractory 
      chronic lymphocytic leukemia (CLL). Eligible patients received 420 mg/day of 
      ibrutinib with escalating doses of BI 836826. BI 836826 was administered in 
      4-week cycles. After Cycle 12, patients achieving complete response (CR), CR with 
      incomplete marrow recovery, or minimal residual disease-negative partial response 
      could continue to receive BI 836826 + ibrutinib every 4 weeks for </= 12 additional 
      cycles. Patients received either 100 mg (n = 3) or 200 mg (n = 3) BI 
      836826 + ibrutinib. In the 100 mg BI 836826 cohort, one patient received two 
      cycles and two patients received 22 cycles of BI 836826. In the 200 mg BI 836826 
      cohort, patients received 12, 16 and 20 cycles of BI 836826, respectively. All 
      patients discontinued BI 836826 and continued ibrutinib outside the trial. No 
      dose-limiting toxicities were reported in the maximum tolerated dose (MTD) 
      evaluation period. As the trial was discontinued before the MTD was reached, the 
      RP2D was not determined. Grade 3/4 adverse events (AEs) were predominantly 
      hematological. Pseudomonal bacteremia was the only drug-related AE of special 
      interest. BI 836826 + ibrutinib did not exceed the MTD at doses up to 200 mg in 
      patients with CLL. However, RP2D and MTD were not formally established, as the 
      sponsor discontinued the trial.
CI  - (c) 2021. The Author(s).
FAU - Danilov, Alexey V
AU  - Danilov AV
AD  - City Of Hope National Medical Center, Duarte, CA, USA.
FAU - Spurgeon, Stephen E
AU  - Spurgeon SE
AD  - Knight Cancer Institute at Oregon Health & Science University, Portland, OR, USA.
FAU - Siddiqi, Tanya
AU  - Siddiqi T
AD  - City Of Hope National Medical Center, Duarte, CA, USA.
FAU - Quinson, Anne-Marie
AU  - Quinson AM
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
FAU - Maier, Daniela
AU  - Maier D
AD  - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
FAU - Smith, Dionne
AU  - Smith D
AD  - Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA.
FAU - Brown, Jennifer R
AU  - Brown JR
AUID- ORCID: 0000-0003-2040-4961
AD  - Dana-Farber Cancer Institute, Boston, MA, USA. Jennifer_Brown@dfci.harvard.edu.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210308
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (BI 836826)
RN  - 0 (CD37 protein, human)
RN  - 0 (Piperidines)
RN  - 0 (Tetraspanins)
RN  - 1X70OSD4VX (ibrutinib)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/administration & dosage/analogs & derivatives
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Antigens, Neoplasm/*immunology
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/pathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Piperidines/administration & dosage
MH  - Tetraspanins/*immunology
PMC - PMC8279974
OTO - NOTNLM
OT  - BI 836826
OT  - CD37
OT  - Chronic lymphocytic leukemia
OT  - Phase Ib
OT  - Relapsed
COIS- AVD has received consulting fees from AstraZeneca, Abbvie, BeiGene, Genentech, TG 
      Therapeutics, Janssen, Rigel Pharmaceutical, Nurix, Bayer Oncology, Karyopharm 
      and Pharmacyclics and has ongoing research funding from AstraZeneca, Takeda 
      Oncology, Gilead Sciences, Bayer Oncology, Genentech, Verastem Oncology, MEI and 
      Bristol Myers Squibb.  SES reports grants from Boehringer Ingelheim during the 
      conduct of the study and personal fees from Pharmacyclics outside the submitted 
      work.  TS reports institutional funds fees from Boehringer Ingelheim during the 
      conduct of the study; personal fees from AstraZeneca, PCYC, Janssen, Juno, 
      Celgene, BeiGene and Kite Pharma outside the submitted work.  AMQ, DM and DS are 
      employees of Boehringer Ingelheim.  JRB reports personal fees from Abbvie, 
      Acerta/AstraZeneca, Astellas, BeiGene, Catapult Therapeutics, Dynamo 
      Therapeutics, Genentech/Roche, Janssen, Juno/Celgene, Kite, MEI Pharma, Nextcea, 
      Novartis, Octapharma, Pfizer, Pharmacyclics, Redx, Rigel, Sun, Sunesis, Teva, and 
      TG Therapeutics; grants and personal fees from Gilead, Loxo/Lilly and Verastem 
      outside the submitted work. She has sat on Data Safety Monitoring Boards for 
      Invectys and Morphosys. 
EDAT- 2021/03/09 06:00
MHDA- 2022/02/03 06:00
PMCR- 2021/03/08
CRDT- 2021/03/08 12:15
PHST- 2020/10/26 00:00 [received]
PHST- 2020/12/16 00:00 [accepted]
PHST- 2021/03/09 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2021/03/08 12:15 [entrez]
PHST- 2021/03/08 00:00 [pmc-release]
AID - 10.1007/s10637-020-01056-4 [pii]
AID - 1056 [pii]
AID - 10.1007/s10637-020-01056-4 [doi]
PST - ppublish
SO  - Invest New Drugs. 2021 Aug;39(4):1099-1105. doi: 10.1007/s10637-020-01056-4. Epub 
      2021 Mar 8.