A Phase I Study of Alisertib + R-EPOCH for Treatment of Myc-Positive Aggressive B-cell Lymphomas
|ClinicalTrials.gov Identifier: NCT02700022|
Recruitment Status : Terminated (Lack of funding)
First Posted : March 7, 2016
Last Update Posted : November 20, 2017
This phase I/Ib study is designed to establish the safety and maximum tolerated dose (MTD, which will also be the recommended phase II dose (RP2D)) of the aurora kinase A inhibitor alisertib when combined with dose-adjusted (DA)-R-EPOCH (rituximab, etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone) in patients with CD20-positive diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma or Burkitt lymphoma positive for Myc gene rearrangement (Myc+). Filgrastim or peg-filgrastim is also included with each cycle of R-EPOCH. Once we identify the MTD, an expansion cohort limited to the Myc+ DLBCL population will be opened to further characterize clinical activity and safety.
Secondary objectives include estimates of complete response rate (CR) and progression free survival (PFS). We will also explore for associations between baseline kinome signatures and/or RNA sequencing and CR, and identify differential kinome and transcriptome prior to and during treatment.
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Large B-cell Lymphoma Follicular Lymphoma Burkitt Lymphoma||Drug: Alisertib||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/Ib Study of Alisertib Plus R-EPOCH for Treatment of Myc-Positive Aggressive B-Cell Lymphomas|
|Actual Study Start Date :||October 2016|
|Actual Primary Completion Date :||November 15, 2016|
|Actual Study Completion Date :||August 18, 2017|
Experimental: Alisertib combined with R-EPOCH
Dose escalation will take place within cohorts. Subjects will receive alisertib tablets twice daily in combination with R-EPOCH chemotherapy on days 1 through 5 of each 21-day cycle. The treatment will be given in 6 cycles. The first 3 patients to be enrolled will receive a 20 milligram (mg) dose of alisertib. The dose of alisertib will be increased or decreased as more subjects enter the study. Each dose level will be evaluated for safety and tolerability before the next higher dose is given. The dose levels will be modified until the maximum tolerated dose (MTD) is reached. Once the MTD has been established, enrollment into that cohort will continue with up to a maximum of 24 patients total enrolled into the study.
Dose escalation of alisertib: level 1 - 20 mg, level 2 - 30 mg, level 3 - 40 mg PO BID on Days 1-5 of six 21-day cycles, combined with R-EPOCH Rituximab, IV infusion on day 1 of each cycle; Etoposide, IV infusion for 96 hours on days 1, 2, 3, and 4 Doxorubicin, IV infusion for 96 hours on days 1, 2, 3, and 4 Vincristine, IV infusion for 96 hours on days 1, 2, 3, and 4 Cyclophosphamide, IV infusion for 15 minutes on day 5 Prednisone, PO daily on days 1, 2, 3, 4, and 5
- Maximum tolerated dose (MTD) [ Time Frame: 2 years ]
- Toxicity [ Time Frame: from day 1 of treatment until up to 2 years after treatment ]Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0
- Rate of Response [ Time Frame: from day 1 of treatment until up to 2 years after treatment ]Rate of CR will be evaluated as defined by The International Harmonization Project for Response Criteria
- Progression free survival [ Time Frame: from day 1 of treatment until up to 2 years after treatment or death, whichever occurs first ]
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): NCT02700022
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|United States, North Carolina|
|University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center|
|Chapel Hills, North Carolina, United States, 27599|
|Principal Investigator:||Christopher Dittus, DO||UNC Lineberger Comprehensive Cancer Center|