Brentuximab Vedotin for Relapsed/Refractory CD30-positive Non-Hodgkin Lymphomas (BRAN)
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|ClinicalTrials.gov Identifier: NCT02280785|
Recruitment Status : Completed
First Posted : November 3, 2014
Last Update Posted : September 6, 2018
Brentuximab vedotin is an antibody-drug conjugate targeting CD30, one of surface antigens expressed in lymphoma cells. Fanale MA, et al. reported the results of a phase I study with weekly dosing of brentuximab vedotin in patients with relapsed/refractory CD30-positive hematologic malignancies (Clin Cancer Res. 2012) showed tumor regression in 85% of patients. Thus, the overall objective response rate was 59% (24/44) including 34% (n = 14) of complete remissions. This study mainly included Hodgkin lymphoma (n = 38) and anaplastic large cell lymphoma (n = 5). However, its efficacy in other types of NHL has never been reported although this study enrolled one patient with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS).
CD30 (TNFRSF8) is a transmembrane glycoprotein of the tumor necrosis factor receptor (TNFR) superfamily, and it is involved in signal transduction via the activation of the NF-κB pathway and the mitogen-activated protein kinases (MAPKs), ultimately modulating cell growth, proliferation and apoptosis. CD30 is a non-lineage-specific activation marker expressed by scattered B and T immunoblasts. In addition, a subset of cases in virtually all T-cell lymphoma entities may also express CD30 but at variable and generally lower levels. In fact, a recent study in 22 patients with extranodal NK/T-cell lymphoma showed 75% of positive rate of CD30 expression (75%). Moreover, CD30 expression was also documented in the tumor sample of EB virus positive diffuse large B-cell lymphomas (EBV + DLBCL) of the elderly (28.9%, 11/38). Therefore, Brentuximab vedotin may have potential benefits for patients with CD30-positive NHL other than anaplastic large cell lymphoma such as CD30-positive PTCLs, NOS. Considering the role of CD30 in signal transduction pathway associated with tumor growth and proliferation, its expression may be associated with tumor aggressiveness. In accordance with this, it is more likely that relapse or refractory NHLs may have CD30 expression, and the potential benefits of this promising agent as a salvage therapy deserve to be further investigated in these patients who have high risk of treatment failure. Thus, we designed a phase II study for relapsed or refractory NHL patients. This study is to explore the safety and activity of dosing once every 3 weeks of Brentuximab vedotin in patients with relapsed or refractory CD30-positive NHL other than anaplastic large cell lymphoma.
|Condition or disease||Intervention/treatment||Phase|
|Non-Hodgkin Lymphoma||Drug: Brentuximab vedotin||Phase 2|
The principal investigator use a Simon two-stage minimax design based on overall response rates. Overall disease control rates will be calculated as the percent of patients that have confirmed complete response (CR) or partial response (PR) or stable disease (SD) by radiographic response including CT and/or PET scans. We assume a P0 as 20%, and designate a target rate (P1) as 40%. Under the error probabilities (α=0.05, β=0.20), eighteen patients will be enrolled in the first stage. If overall disease control rate is ≤ 4/18 in the first stage, this study will be stopped. If not, this study will recruit patients up to 33 considering 20% of drop out rate.
Intent-to-treat analysis will be applied to all primary and secondary efficacy endpoints. Response rate will be analyzed based on the response criteria according to Cheson 2007 (Cheson BD, et al. J Clin Oncol 2007; 25 (5):579-586), and data related to overall response rate will be analyzed by statistical analysis including Chi test to evaluate predictive factors for response to study drug.
Overall rate of disease control : CR, PR and SD Progression-free survival : Time between the date of treatment start and the date of death due to any cause or date of disease progression (Up to 36months) Data related to survival rate for all patients will be analyzed based on log-rank test by the Kaplan-Meier method.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||33 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Brentuximab Vedotin for Relapsed/Refractory CD30-positive Non-Hodgkin Lymphomas Other Than Anaplastic Large Cell Lymphoma|
|Actual Study Start Date :||November 2014|
|Actual Primary Completion Date :||December 2017|
|Actual Study Completion Date :||September 2018|
Experimental: Brentuximab vedotin
Brentuximab vedotin administered in 250ml of 0.9% saline by intravenous infusion over 30 minutes once every 3 weeks.
In the absence of infusion toxicities, the infusion rate for all patients must be calculated in order to achieve a 30-minute (approximate) infusion period.
Brentuximab Vedotin is dosed at 1.8mg/kg (capped at 100kg of body weight). Dosing is based on patients' weight according to the institutional standard; however, doses will be adjusted for patients who experience a ≥ 10% change in weight from baseline. Actual weight will be used except for patients weighing greater than 100 kg; dose will be calculated based on 100 kg for these individuals. The dose will be rounded to the nearest whole number of milligrams.
Drug: Brentuximab vedotin
Brentuximab vedotin must not be administered as an IV push or bolus. It must be administered in 100ml-250ml of 0.9% saline by intravenous infusion over 30 minutes once every 3 weeks.
Other Name: Adcetris
- Overall disease control rate [ Time Frame: Until the disease progression (maximum 2 years after completion of treatment, assessed up to 36 months) ]The percentage of subjects with complete response (CR) or partial response (PR) or stable disease (SD)
- Progression-free survival (PFS) [ Time Frame: Time between the date of treatment start and the date of death due to any cause or date of disease progression, whichever came first, assessed up to 36months ]
- Toxicity (assessed by analyzing adverse events and the standard clinical laboratory and hematologic findings.) [ Time Frame: From the date of first drug administration until the date of the 30th days, assessed up to 13 months ]Toxicity will be assessed by analyzing adverse events and the standard clinical laboratory and hematologic findings.
- Overall survival (OS) [ Time Frame: Time between the date of treatment start and the date of death due to any cause,assessed up to 36 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02280785
|Korea, Republic of|
|National Cancer Center|
|Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769|
|Yonsei Severance Hospital|
|Seoul, Korea, Republic of, 120-752|
|Asan Medical Center|
|Seoul, Korea, Republic of, 138-736|
|Korean Cancer Center Hospital|
|Seoul, Korea, Republic of, 139-706|
|Principal Investigator:||Cheolwon Suh, M.D.||Asan Medical Center|
|Principal Investigator:||JinSeok Kim, M.D.||Severance Hospital|
|Principal Investigator:||HyeonSeok Eom, M.D.||National Cancer Center of Korea|
|Principal Investigator:||HyeJin Kang, M.D.||Korea Cancer Center Hospital|