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Brander, Danielle Marie

Positions:

Assistant Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2007

M.D. — Duke University School of Medicine

Grants:

Ph 2 Study of TGR-1202 in Patients with CLL

Administered By
Duke Cancer Institute
AwardedBy
TG Therapeutics, Inc
Role
Principal Investigator
Start Date
September 01, 2016
End Date
September 01, 2021

Multi-Center, Open-Label Study of Ublituximab (TG-1101) in combination with TGR-1202

Administered By
Duke Cancer Institute
AwardedBy
TG Therapeutics, Inc
Role
Principal Investigator
Start Date
September 01, 2016
End Date
August 31, 2021

Ph 3 of Ublituximab in Combination with TGR-1202

Administered By
Duke Cancer Institute
AwardedBy
TG Therapeutics, Inc
Role
Principal Investigator
Start Date
September 01, 2016
End Date
August 31, 2021

Phase III study of ACP-196 vs Ibrutinib in High Risk CLL

Administered By
Duke Cancer Institute
AwardedBy
Acerta Pharma
Role
Principal Investigator
Start Date
June 01, 2016
End Date
May 31, 2021

A Phase II Study of Ibrutinib in combo with Fludarabine, Cyclophosphamide and Rituximab for young patients with CLL

Administered By
Duke Cancer Institute
AwardedBy
Dana Farber Cancer Institute
Role
Principal Investigator
Start Date
October 01, 2015
End Date
September 30, 2020

Phase 3 Study of Ublituximab in combination with Ibrutinib compared to Ibrutinib Alone in CLL pts.

Administered By
Duke Cancer Institute
AwardedBy
TG Therapeutics, Inc
Role
Principal Investigator
Start Date
March 01, 2015
End Date
February 29, 2020

Gilead GS-US 312 0133

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
Gilead Sciences, Inc.
Role
Principal Investigator
Start Date
November 10, 2014
End Date
November 09, 2019

DFCI Obinutuzumab and Ibrutinib Protocol # 15-283

Administered By
Duke Cancer Institute
AwardedBy
Dana Farber Cancer Institute
Role
Principal Investigator
Start Date
November 03, 2017
End Date
April 09, 2019

Screening protocol to determine high risk cytogenetic features in previously treated CLL

Administered By
Duke Cancer Institute
AwardedBy
TG Therapeutics, Inc
Role
Principal Investigator
Start Date
July 01, 2016
End Date
October 19, 2017

A Phase II Study of PNT2258 in Patients with Richter's Transformation (RT).

Administered By
Duke Cancer Institute
AwardedBy
ProNAi Therapeutics, Inc.
Role
Principal Investigator
Start Date
January 01, 2016
End Date
October 11, 2017

MedImmune CD-ON-CAT-8015-1053

Administered By
Duke Cancer Institute
AwardedBy
MedImmune, Inc.
Role
Principal Investigator
Start Date
February 01, 2015
End Date
October 11, 2017

GS-US-312-0123

Administered By
Duke Cancer Institute
AwardedBy
Gilead Sciences, Inc.
Role
Principal Investigator
Start Date
August 11, 2014
End Date
October 11, 2017

A Phase I Trial of a Bcl-2 inhibitor and a MEK inhibitor for patients with relapsed indolent B-NHL

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
AwardedBy
Lymphoma Research Foundation of America
Role
Principal Investigator
Start Date
January 15, 2014
End Date
May 15, 2016

Phase 2 GS-US-339-0103

Administered By
Duke Cancer Institute
AwardedBy
Gilead Sciences, Inc.
Role
Principal Investigator
Start Date
December 30, 2013
End Date
June 22, 2015
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Publications:

Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study.

Selective BCL2 inhibition with venetoclax has substantial activity in patients with relapsed or refractory chronic lymphocytic leukaemia. Combination therapy with rituximab enhanced activity in preclinical models. The aim of this study was to assess the safety, pharmacokinetics, and activity of venetoclax in combination with rituximab.Adult patients with relapsed or refractory chronic lymphocytic leukaemia (according to the 2008 Modified International Workshop on CLL guidelines) or small lymphocytic lymphoma were eligible for this phase 1b, dose-escalation trial. The primary outcomes were to assess the safety profile, to determine the maximum tolerated dose, and to establish the recommended phase 2 dose of venetoclax when given in combination with rituximab. Secondary outcomes were to assess the pharmacokinetic profile and analyse efficacy, including overall response, duration of response, and time to tumour progression. Minimal residual disease was a protocol-specified exploratory objective. Central review of the endpoints was not done. Venetoclax was dosed daily using a stepwise escalation to target doses (200-600 mg) and then monthly rituximab commenced (375 mg/m2 in month 1 and 500 mg/m2 in months 2-6). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for adverse events version 4.0. Protocol-guided drug cessation was allowed for patients who achieved complete response (including complete response with incomplete marrow recovery) or negative bone marrow minimal residual disease. Analyses were done per protocol for all patients who commenced drug and included all patients who received at least one dose of venetoclax. Data were pooled across dose cohorts. Patients are still receiving therapy and follow-up is ongoing. The trial is registered at ClinicalTrials.gov, number NCT01682616.Between Aug 6, 2012, and May 28, 2014, we enrolled 49 patients. Common grade 1-2 toxicities included upper respiratory tract infections (in 28 [57%] of 49 patients), diarrhoea (27 [55%]), and nausea (25 [51%]). Grade 3-4 adverse events occurred in 37 (76%) of 49 patients; most common were neutropenia (26 [53%]), thrombocytopenia (eight [16%]), anaemia (seven [14%]), febrile neutropenia (six [12%]), and leucopenia (six [12%]). The most common serious adverse events were pyrexia (six [12%]), febrile neutropenia (five [10%]), lower respiratory tract infection, and pneumonia (each three [6%]). Clinical tumour lysis syndrome occurred in two patients (resulting in one death) who initiated venetoclax at 50 mg. After enhancing tumour lysis syndrome prophylaxis measures and commencing venetoclax at 20 mg, clinical tumour lysis syndrome did not occur. The maximum tolerated dose was not identified; the recommended phase 2 dose of venetoclax in combination with rituximab was 400 mg. Overall, 42 (86%) of 49 patients achieved a response, including a complete response in 25 (51%) of 49 patients. 2 year estimates for progression-free survival and ongoing response were 82% (95% CI 66-91) and 89% (95% CI 72-96), respectively. Negative marrow minimal residual disease was attained in 20 (80%) of 25 complete responders and 28 (57%) of 49 patients overall. 13 responders ceased all therapy; among these all 11 minimal residual disease-negative responders remain progression-free off therapy. Two with minimal residual disease-positive complete response progressed after 24 months off therapy and re-attained response after re-initiation of venetoclax.A substantial proportion of patients achieved an overall response with the combination of venetoclax and rituximab including 25 (51%) of 49 patients who achieved a complete response and 28 (57%) of 49 patients who achieved negative marrow minimal residual disease with acceptable safety. The depth and durability of responses observed with the combination offers an attractive potential treatment option for patients with relapsed or refractory chronic lymphocytic leukaemia and could allow some patients to maintain response after discontinuing therapy, a strategy that warrants further investigation in randomised studies.AbbVie Inc and Genentech Inc.

Authors
Seymour, JF; Ma, S; Brander, DM; Choi, MY; Barrientos, J; Davids, MS; Anderson, MA; Beaven, AW; Rosen, ST; Tam, CS; Prine, B; Agarwal, SK; Munasinghe, W; Zhu, M; Lash, LL; Desai, M; Cerri, E; Verdugo, M; Kim, SY; Humerickhouse, RA; Gordon, GB; Kipps, TJ; Roberts, AW
MLA Citation
Seymour, JF, Ma, S, Brander, DM, Choi, MY, Barrientos, J, Davids, MS, Anderson, MA, Beaven, AW, Rosen, ST, Tam, CS, Prine, B, Agarwal, SK, Munasinghe, W, Zhu, M, Lash, LL, Desai, M, Cerri, E, Verdugo, M, Kim, SY, Humerickhouse, RA, Gordon, GB, Kipps, TJ, and Roberts, AW. "Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study." The Lancet. Oncology 18.2 (February 2017): 230-240.
PMID
28089635
Source
epmc
Published In
The Lancet Oncology
Volume
18
Issue
2
Publish Date
2017
Start Page
230
End Page
240
DOI
10.1016/s1470-2045(17)30012-8

Rationale for combinatory chronic lymphocytic leukaemia treatment paradigms in the era of the B-cell receptor pathway and anti-apoptotic inhibitors: how do we mix, match, and move forward?

Authors
Brander, DM
MLA Citation
Brander, DM. "Rationale for combinatory chronic lymphocytic leukaemia treatment paradigms in the era of the B-cell receptor pathway and anti-apoptotic inhibitors: how do we mix, match, and move forward?." British Journal of Haematology 176.3 (February 2017): 337-340.
Source
crossref
Published In
British Journal of Haematology
Volume
176
Issue
3
Publish Date
2017
Start Page
337
End Page
340
DOI
10.1111/bjh.14446

Ofatumumab monotherapy as a consolidation strategy in patients with previously untreated chronic lymphocytic leukaemia: a phase 2 trial

Authors
Strati, P; Lanasa, M; Call, TG; Leis, JF; Brander, DM; LaPlant, BR; Pettinger, AM; Ding, W; Parikh, SA; Hanson, CA; Chanan-Khan, AA; Bowen, DA; Conte, M; Kay, NE; Shanafelt, TD
MLA Citation
Strati, P, Lanasa, M, Call, TG, Leis, JF, Brander, DM, LaPlant, BR, Pettinger, AM, Ding, W, Parikh, SA, Hanson, CA, Chanan-Khan, AA, Bowen, DA, Conte, M, Kay, NE, and Shanafelt, TD. "Ofatumumab monotherapy as a consolidation strategy in patients with previously untreated chronic lymphocytic leukaemia: a phase 2 trial." The Lancet Haematology 3.9 (September 2016): e407-e414.
Source
crossref
Published In
The Lancet. Haematology
Volume
3
Issue
9
Publish Date
2016
Start Page
e407
End Page
e414
DOI
10.1016/S2352-3026(16)30064-3

Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies.

Abstract Because of the importance of the phosphoinositide 3-kinase (PI3K)/AKT pathway in chronic lymphocytic leukemia (CLL), we evaluated in vitro cytotoxicity induced by perifosine, an AKT inhibitor, in CLL lymphocytes and found that the mean 50% effective dose (ED50) was 313 nM. We then performed a phase II trial of perifosine in patients with relapsed/refractory CLL to assess response, outcomes, toxicity and ex vivo correlative measures. After 3 months of treatment, six of eight patients showed stable disease, one achieved a partial response and one had progressive disease. Median event-free survival and overall survival in all patients treated were 3.9 and 9.7 months. Adverse events included hematologic, infectious/fever, pain, gastrointestinal and constitutional toxicities. Unexpectedly, AKT phosphorylation in CLL lymphocytes from treated patients was not correlated with response. Additionally, perifosine did not inhibit AKT phosphorylation in cultured CLL lymphocytes. Perifosine is cytotoxic to CLL cells in vitro, and largely induces stabilized disease in vivo, with an AKT-independent mechanism.

Authors
Friedman, DR; Lanasa, MC; Davis, PH; Allgood, SD; Matta, KM; Brander, DM; Chen, Y; Davis, ED; Volkheimer, AD; Moore, JO; Gockerman, JP; Sportelli, P; Weinberg, JB
MLA Citation
Friedman, DR, Lanasa, MC, Davis, PH, Allgood, SD, Matta, KM, Brander, DM, Chen, Y, Davis, ED, Volkheimer, AD, Moore, JO, Gockerman, JP, Sportelli, P, and Weinberg, JB. "Perifosine treatment in chronic lymphocytic leukemia: results of a phase II clinical trial and in vitro studies." Leuk Lymphoma 55.5 (May 2014): 1067-1075.
PMID
23863122
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
55
Issue
5
Publish Date
2014
Start Page
1067
End Page
1075
DOI
10.3109/10428194.2013.824080

Phase II open label study of the oral vascular endothelial growth factor-receptor inhibitor PTK787/ZK222584 (vatalanib) in adult patients with refractory or relapsed diffuse large B-cell lymphoma.

PTK787/ZK222584 (vatalanib), an orally active inhibitor of vascular endothelial growth factor receptors (VEGFRs), was evaluated in this phase II study of 20 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received once-daily PTK787/ZK222584 at a target dose of 1250 mg. Eighteen patients were evaluable for response: one patient had a complete response (CR), six patients had stable disease but subsequently progressed, 10 patients had progressive disease by three cycles and one subject withdrew before response evaluation. The patient who attained a CR underwent autologous stem cell transplant and remains disease-free 76 months after study completion. There were no grade 4 toxicities. Grade 3 thrombocytopenia occurred in 20% and grade 3 hypertension occurred in 10%. There were no episodes of grade 3 proteinuria. In conclusion, PTK787/ZK222584 was well tolerated in a heavily pretreated population of patients with DLBCL, although its therapeutic potential as a single agent in DLBCL appears limited.

Authors
Brander, D; Rizzieri, D; Gockerman, J; Diehl, L; Shea, TC; Decastro, C; Moore, JO; Beaven, A
MLA Citation
Brander, D, Rizzieri, D, Gockerman, J, Diehl, L, Shea, TC, Decastro, C, Moore, JO, and Beaven, A. "Phase II open label study of the oral vascular endothelial growth factor-receptor inhibitor PTK787/ZK222584 (vatalanib) in adult patients with refractory or relapsed diffuse large B-cell lymphoma." Leuk Lymphoma 54.12 (December 2013): 2627-2630.
PMID
23488610
Source
pubmed
Published In
Leukemia & Lymphoma (Informa)
Volume
54
Issue
12
Publish Date
2013
Start Page
2627
End Page
2630
DOI
10.3109/10428194.2013.784969

Update on treatment of follicular non-Hodgkin's lymphoma: focus on potential of bortezomib.

Follicular lymphoma is predominantly managed as a chronic disease, with intermittent chemo/immunotherapy reserved for symptomatic progression. It is considered incurable with conventional treatments, and current therapeutic options are associated with significant toxicities that are especially limiting in older patients. Bortezomib (PS-341; Velcade(®)), a first-in-class drug targeting the proteolytic core subunit of the 26S proteasome, has emerged as a therapeutic alternative in follicular lymphoma, with promising preclinical data and efficacy in patients with other hematological malignancies. Several clinical trials were conducted with bortezomib for the treatment of non-Hodgkin's lymphoma. As a single agent, overall responses in follicular lymphoma varied greatly (16%-41%), with weekly bortezomib showing less neurotoxicity than twice-weekly regimens, but with concern about decreased responses. Combination with rituximab was projected to improve the efficacy of bortezomib, but this resulted in increased toxicities and questionable added benefit. Although the largest Phase III study in follicular lymphoma of bortezomib plus rituximab versus rituximab alone demonstrated a significant progression-free survival difference, the absolute difference was small (12.8 months versus 11 months). Combining bortezomib with established regimens, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), or rituximab-bendamustine also did not show definite benefit, and many of these studies did not meet their primary endpoint when bortezomib failed to improve responses or survival to the degree anticipated. In a disease where the goal of treatment is palliative and affected patients often have other medical and treatment-related comorbidities, decisions regarding therapies which carry risks of additional toxicities must be considered carefully. Conclusive evidence of the ability of bortezomib to improve patient outcomes meaningfully and to justify the added toxicity is lacking, but limitations in cross-trial comparisons are recognized. Large randomized trials and investigations of combinations with promising novel targeted agents will aid in determining the role of bortezomib, if any, in the future treatment of follicular lymphoma.

Authors
Brander, DM; Beaven, AW
MLA Citation
Brander, DM, and Beaven, AW. "Update on treatment of follicular non-Hodgkin's lymphoma: focus on potential of bortezomib." Patient preference and adherence 6 (January 2012): 239-251.
PMID
22536060
Source
epmc
Published In
Patient Preference and Adherence
Volume
6
Publish Date
2012
Start Page
239
End Page
251
DOI
10.2147/ppa.s23241

Morphologically normal-appearing mammary epithelial cells obtained from high-risk women exhibit methylation silencing of INK4a/ARF.

PURPOSE: p16(INK4a) has been appreciated as a key regulator of cell cycle progression and senescence. Cultured human mammary epithelial cells that lack p16(INK4a) activity have been shown to exhibit premalignant phenotypes, such as telomeric dysfunction, centrosomal dysfunction, a sustained stress response, and, most recently, a dysregulation of chromatin remodeling and DNA methylation. These data suggest that cells that lack p16(INK4a) activity would be at high risk for breast cancer development and may exhibit an increased frequency of DNA methylation events in early cancer. EXPERIMENTAL DESIGN: To test this hypothesis, the frequencies of INK4a/ARF promoter hypermethylation, as well as four additional selected loci, were tested in the initial random periareolar fine needle aspiration samples from 86 asymptomatic women at high risk for development of breast cancer, stratified using the Masood cytology index. RESULTS: INK4a/ARF promoter hypermethylation was observed throughout all early stages of intraepithelial neoplasia and, importantly, in morphologically normal-appearing mammary epithelial cells; 29 of 86 subjects showed INK4a/ARF promoter hypermethylation in at least one breast. Importantly, INK4a/ARF promoter hypermethylation was not associated with atypia, and the frequency of hypermethylation did not increase with increasing Masood cytology score. The frequency of INK4a/ARF promoter hypermethylation was associated with the combined frequency of promoter hypermethylation of retinoic acid receptor-beta2, estrogen receptor-alpha, and breast cancer-associated 1 genes (P = 0.001). CONCLUSIONS: Because INK4a/ARF promoter hypermethylation does not increase with age but increases with the frequency of other methylation events, we predict that INK4a/ARF promoter hypermethylation may serve as a marker of global methylation dysregulation.

Authors
Bean, GR; Bryson, AD; Pilie, PG; Goldenberg, V; Baker, JC; Ibarra, C; Brander, DMU; Paisie, C; Case, NR; Gauthier, M; Reynolds, PA; Dietze, E; Ostrander, J; Scott, V; Wilke, LG; Yee, L; Kimler, BF; Fabian, CJ; Zalles, CM; Broadwater, G; Tlsty, TD; Seewaldt, VL
MLA Citation
Bean, GR, Bryson, AD, Pilie, PG, Goldenberg, V, Baker, JC, Ibarra, C, Brander, DMU, Paisie, C, Case, NR, Gauthier, M, Reynolds, PA, Dietze, E, Ostrander, J, Scott, V, Wilke, LG, Yee, L, Kimler, BF, Fabian, CJ, Zalles, CM, Broadwater, G, Tlsty, TD, and Seewaldt, VL. "Morphologically normal-appearing mammary epithelial cells obtained from high-risk women exhibit methylation silencing of INK4a/ARF." Clinical cancer research : an official journal of the American Association for Cancer Research 13.22 Pt 1 (November 2007): 6834-6841.
PMID
18006786
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
22 Pt 1
Publish Date
2007
Start Page
6834
End Page
6841
DOI
10.1158/1078-0432.ccr-07-0407
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