A Study of BNC105P Combined With Ibrutinib
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|ClinicalTrials.gov Identifier: NCT03454165|
Recruitment Status : Recruiting
First Posted : March 5, 2018
Last Update Posted : June 6, 2019
A Phase I Trial of BNC105P in combination with BTK inhibitor ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia(CLL). This study proposes that ibrutinib will have far greater efficacy when it is combined with drugs that kill the CLL cells in peripheral circulation, thereby preventing them from returning to the protective lymph node niche. The study will establish the maximum tolerated dose(MTD) of the combination of BNC105P with ibrutinib, characterize the pharmacodynamic effects of BNC105P alone and in combination with ibrutinib in CLL cells, and provide preliminary assessment of the efficacy of the combination in CLL.
The study consists of a Screening Period with baseline tumor assessment before BNC105P administration, a Treatment Period with up to six 21-day cycles and Follow-up Period. Subjects will receive a total of six cycles of therapy unless treatment is discontinued
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia||Combination Product: BNC105P Combination Product: Ibrutinib||Phase 1|
A Phase I Trial of BNC105P in combination with BTK inhibitor ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Ibrutinib inhibits the pro-survival BCR signaling of CLL cells in the stromal niche resulting in their egress to the periphery. Importantly, if administration of ibrutinib is stopped, the CLL cells rapidly return to the lymph node. In some patients, the drug-induced increase in circulating CLL cells has been seen for more than a year reflecting the fact that the cells do not readily die once they exit the lymph node. Resistance to ibrutinib has been observed as mutations in the drug-binding cysteine in its target, BTK. This resistance is likely to become far more prevalent as patients remain on ibrutinib for months or years. We propose that ibrutinib will have far greater efficacy when it is combined with drugs that kill the CLL cells in peripheral circulation, thereby preventing them from returning to the protective lymph node niche. BNC105P works through an entirely different mechanism, i.e. tipping the balance of pro-survival and pro-apoptotic BCL2 family member proteins toward the latter, resulting in cell death. This pathway of apoptosis occurs at all stages of the cell cycle which is important considering that the majority of peripheral CLL cells are non-cycling (in G0).
The study consists of a Screening Period with baseline tumor assessment before BNC105P administration, a Treatment Period with up to six 21-day cycles and Follow-up Period. Subjects will receive a total of six cycles of therapy unless treatment is discontinued.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Open label dose escalation study, with a Storer D ; 3-3 cohort design|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Trial of BNC105P & Ibrutinib in Patients w/ Relapsed/Refractory CLL|
|Actual Study Start Date :||March 9, 2018|
|Estimated Primary Completion Date :||February 2020|
|Estimated Study Completion Date :||December 2020|
Experimental: Single Arm
Evaluate the MTD of BNC105P in combination with ibrutinib in patients with relapsed/refractory CLL. Treatment will be administered on an outpatient basis but will also be permitted inpatient. BNC105P will be administered as a single agent prior to initiation of ibrutinib. Beginning with cycle 2, ibrutinib will be administered concomitantly with BNC105P at a starting dose of 420 mg PO daily. Each cycle will last for 21 days. Provided no toxicities occur, each patient will be treated for 6 cycles.
Combination Product: BNC105P
BNC105P is the phosphate ester of BNC105, a small molecule tubulin polymerization inhibitor.
Combination Product: Ibrutinib
A novel BTK inhibitor.
- To establish the maximum tolerated dose and toxicity of BNC105P plus Ibrutinib [ Time Frame: Two years ]The number of relapsed refractory chronic lymphatic leukemia patients, in cohorts of 3-6, who develop treatment related adverse effects from combined therapy with BNC105P and ibrutinib. The treatment related adverse events will be defined based on CTCAE v 4.0
- Evaluating the efficacy of BNC105P combined with Ibrutinib in patients with CLL [ Time Frame: Two years ]The number of relapsed refractory CLL patients in each dosing cohort (n= 3-6 patients) who when treated with BNC105P combined with ibrutinib will have therapeutic benefit based on CLL response criteria using CT imaging
- Determine the Overall Response Rate (ORR) [ Time Frame: Two years ]
Overall response rate (ORR) will be determined based on the number of study participants who achieve CR, CRi, PR or nPR assessed two months after completion of therapy, as per IWCLL 2008 criteria.
The timeframe is consistent with the Measure Title
- Determine the event free survival [ Time Frame: Two years ]Event-free survival (EFS), defined as the interval between the date of first study treatment and the date of objective signs of disease recurrence, subsequent anti-leukemic therapy, or death, whichever is first reported.
- Explore the effects of BNC105P and BNC105P + Ibrutinib on NOXA and JNK in Chronic Lymphocytic Leukemia Cells [ Time Frame: Two years ]Study the effects of BNC105P as monotherapy and when used in combination with ibrutinib on the activation of NOXA and JNK in chronic lymphocytic leukemia cells using Western blots.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03454165
|Contact: Bridget M Labrie, MBAfirstname.lastname@example.org|
|Contact: Brian Highhouse, RNemail@example.com|
|United States, New Hampshire|
|Dartmouth-Hitchcock Medical Center||Recruiting|
|Lebanon, New Hampshire, United States, 03756|
|Contact: Lionel D Lewis, MD 603-650-7811|
|Contact: Bridget M Labrie, MBA 603-650-6227 firstname.lastname@example.org|
|Principal Investigator:||Lionel D Lewis, MD||Dartmouth-Hitchcock Medical Center|