Combination Chemotherapy and TAK-659 as Front-Line Treatment in Treating Patients With High-Risk Diffuse Large B Cell Lymphoma
|ClinicalTrials.gov Identifier: NCT03742258|
Recruitment Status : Recruiting
First Posted : November 15, 2018
Last Update Posted : March 15, 2019
The purpose of this research study is to evaluate a new investigational drug, TAK-659, given in combination with standard chemotherapy, for the treatment of Diffuse Large B-cell Lymphoma (DLBCL). ?Investigational? means that TAK-659 has not been approved by the United States Food and Drug Administration (FDA) for use as a prescription or over-the-counter medication to treat a certain condition. The primary purpose of this study is to find the appropriate and safe dose of the study drug to be used in combination with standard chemotherapy for the treatment of your disease and to determine how well the drug works in treating the disease. Other objectives include measuring the amount of the study drug in the body at different times after taking the study drug.
Participation in the study is expected to last for up to 3 years after receiving the last dose of the study drug. Patients will receive the study treatment for up to 18 weeks, as long as they are benefitting.
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Large B-Cell Lymphoma Diffuse Large B-Cell Lymphoma Activated B-Cell Type Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type Diffuse Large B-Cell Lymphoma, Not Otherwise Specified High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements High Grade B-Cell Lymphoma, Not Otherwise Specified T-Cell/Histiocyte-Rich Large B-Cell Lymphoma||Drug: Cyclophosphamide Drug: Doxorubicin Hydrochloride Drug: Prednisone Biological: Rituximab Drug: Spleen Tyrosine Kinase Inhibitor TAK-659 Drug: Vincristine Sulfate||Phase 1|
I. To determine the safety, tolerability, and maximum tolerated dose of TAK-659 when combined with R-CHOP in the front-line treatment of high-risk diffuse large B cell lymphoma (DLBCL).
I. To assess preliminary efficacy of TAK-659 combined with R-CHOP in the front-line treatment of high-risk DLBCL.
I. To characterize the pharmacokinetics (PK) of TAK-659 in combination with R-CHOP.
OUTLINE: This is a dose-escalation study of spleen tyrosine kinase inhibitor TAK-659.
Patients receive rituximab intravenously (IV), cyclophosphamide IV, doxorubicin hydrochloride IV over 3-5 minutes, and vincristine sulfate IV on day 1, and prednisone orally (PO) on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning in course 2, patients also receive spleen tyrosine kinase inhibitor TAK-659 PO once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for up to 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of R-CHOP Plus SYK Inhibitor TAK-659 for the Front-Line Treatment of High-Risk Diffuse Large B Cell Lymphoma (DLBCL)|
|Actual Study Start Date :||March 13, 2019|
|Estimated Primary Completion Date :||August 1, 2021|
|Estimated Study Completion Date :||August 1, 2022|
Experimental: Treatment (R-CHOP, TAK-659)
Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV over 3-5 minutes, and vincristine sulfate IV on day 1, and prednisone PO on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning in course 2, patients also receive spleen tyrosine kinase inhibitor TAK-659 PO QD on days 1-21. Treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.
Drug: Doxorubicin Hydrochloride
Drug: Spleen Tyrosine Kinase Inhibitor TAK-659
Drug: Vincristine Sulfate
- Incidence and grade of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities [ Time Frame: Up to 30 days post-treatment ]Toxicity and tolerability will be assessed by history and physical, including vital signs and Eastern Cooperative Oncology Group (ECOG) performance status, and laboratory values to determine incidence and grade of AEs, SAEs, and dose-limiting toxicities, as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
- Overall response rate (ORR) [ Time Frame: Up to 30 days post-treatment ]Using Lugano criteria (2014), ORR will be defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) as assessed by the investigators. Response will be assessed by positron emission tomography (PET)/computed tomography (CT).
- Progression free survival (PFS) [ Time Frame: From study enrollment until progression/recurrence of lymphoma or death from any cause, assessed up to 3 years ]PFS will be assessed using Kaplan-Meier curves.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03742258
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Contact: Reem Karmali 312-695-0711 firstname.lastname@example.org|
|Principal Investigator: Reem Karmali|
|Principal Investigator:||Reem Karmali||Northwestern University|