Alsertib (MLN8237) and Brentuximab Vedotin for Relapsed/Refractory CD30-Positive Lymphomas and Solid Malignancies (AD3LE)
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|ClinicalTrials.gov Identifier: NCT02780011|
Recruitment Status : Withdrawn (lack of funding)
First Posted : May 23, 2016
Last Update Posted : July 27, 2018
|Condition or disease||Intervention/treatment||Phase|
|CD30-positive Lymphoma CD30-positive Solid Tumor||Drug: Brentuximab Vedotin Drug: Alsertib||Phase 1|
This is an investigator-initiated, open label phase I trial designed to evaluate the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and activity of brentuximab vedotin in combination with MLN8237 in patients with relapsed/refractory CD30-positive lymphomas and solid malignancies.
Brentuximab vedotin at a fixed dose of 1.8 mg/kg will be administered on Day 1 every three weeks as a 30-minute outpatient intravenous infusion. MLN8237 will be orally administered in two divided doses from Days 1-7. The starting dose (level 0) of MLN8237 will be 60 mg daily given in two divided doses (30 mg qAM, 30 mg qPM).The dose of MLN8237 will be escalated in 20-mg increments up to 100 mg daily and de-escalated in 20-mg decrements to 40 mg daily. The fixed dose of brentuximab vedotin on Day 1 and daily dose of MLN8237 on Day 1-7 will constitute one treatment cycle. If no DLTs are observed in the last study cohort, the cohort will be expanded to include a total of 12 patients. If a de-escalation dose is required because 2 or more patients experience DLTs, the next lower cohort will be studied. If 2 or more patients do not experience DLTs, this dose will be declared the MTD. This cohort will be expanded to include 12 patients in order to study the biological endpoints and clinical benefit of the combination. If at any point during the expansion cohort phase of the trial 33% or more of the patients treated at the MTD/maximum administered dose experience a DLT, accrual of additional patients at this does level will cease and the next lowest dose may be explored.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of the Combination of Alsertib (MLN8237) and Brentuximab Vedotin in Relapsed/Refractory CD30-Positive Lymphomas and Solid Malignancies|
|Study Start Date :||December 2015|
|Estimated Primary Completion Date :||September 2018|
|Estimated Study Completion Date :||September 2018|
Experimental: Alsertib and Brentuximab Vedotin
Brentuximab vedotin at a fixed dose of 1.8 mg/kg will be administered by intravenous infusion on day 1 of every 21-day cycle. MLN8237 at a dose of 60 mg will be orally administered daily in 2 divided doses (30 mg qAM, 30 mg qPM) from days 1 to 7 of each 21-day cycle. MLN8237 dose will be escalated in 20-mg increments to the maximum dose of 100 mg (Level 2) or de-escalated in a 20-mg decrement to the minimum dose of 40 mg (Level -1).
Drug: Brentuximab Vedotin
Antibody-drug conjugate composed of the anti-CD30 chimeric immunoglobulin G1 monoclonal antibody cAC10 and the antimicrotubule drug monomethyl auristatin E connected by a protease-cleavable linker.
Other Name: Adcetris
Aurora A kinase inhibitor
Other Name: MLN8237
- Maximum tolerated dose (MTD) [ Time Frame: Approximately 12 weeks ]Determine the MTD of the alsertib (MLN8237) and brentuximab vedotin combination in patients with relapsed/refractory CD30-positive lymphomas and solid malignancies.
- Dose-limiting toxicities (DLTs) [ Time Frame: Approximately 12 weeks ]Describe the DLTs and other toxicities associated with the alsertib (MLN8237) and brentuximab vedotin combination as assessed by CTCAE v4.0.
- Recommended phase 2 dose (RP2D) [ Time Frame: Approximately 12 weeks ]Determine the RP2D of the alsertib (MLN8237) and brentuximab vedotin combination.
- Antitumor activity [ Time Frame: Approximately 12 weeks ]Document the antitumor activity of the alsertib (MLN8237) and brentuximab vedotin combination as assessed by modified IWG criteria and RECIST 1.1.
- Area under the plasma concentration versus time curve [ Time Frame: Cycle 1, Day 1 at pre-infusion and 10 min, 24 h, and 48 h post-infusion; trough sample on Cycle 1, Day 8; and Cycle 2, Day 1 at pre-infusion and 12 h and 24 h post-infusion. ]Determine the area under the plasma concentration versus time curve of alsertib (MLN8237) and brentuximab vedotin.
- H3K activity [ Time Frame: Approximately 12 weeks ]Measure H3K activity in peripheral blood mononuclear cells and tumor tissue following treatment with the combination of alsertib (MLN8237) and brentuximab vedotin.
- Correlation between CD30 detection method and clinical response [ Time Frame: Approximately 12 weeks ]Explore the correlation between CD30 detection method (aptamer-mediated flow cytometric detection vs. immunohistochemical detection) and clinical response to the combination of alsertib (MLN8237) and brentuximab vedotin.
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): NCT02780011
|United States, Texas|
|Houston Methodist Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Swami Padmanabhan Iyer, MD||The Methodist Hospital Research Institute|