Combination Chemotherapy and TAK-659 as Front-Line Treatment in Treating Patients With High-Risk Diffuse Large B Cell Lymphoma

Completed · Phase 1

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT03742258

Run by

Northwestern University

People needed

12

Starts

2019-03-13

Expected to finish

2024-02-08

Last updated by the study team

2025-06-18

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have a pathologically confirmed diagnosis of DLBCL (including DLBCL not otherwise specified [NOS], DLBCL germinal center B-cell [GCB] type, DLBCL activated B cell [ABC]/non-GCB type, T cell/histiocyte-rich large B cell lymphoma, high-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B cell lymphoma NOS). NOTE: DLBCL transformed from low-grade lymphoma among treatment-naive patients or patients previously treated with a non-anthracycline containing regimen are permitted
• Patients may have completed the first cycle of R-CHOP (off study not combined with TAK-659) =< 21 days prior to the first dose of TAK-659 or plan to receive the first cycle of R-CHOP after registration
• Patients must have at least one high-risk feature, including:
• ABC/non-GCB subtype determined by gene expression profiling or Hans algorithm by immunohistochemistry per treating institution standards
• High-intermediate or high-risk group by National Comprehensive Cancer Network - International Prognostic Index (NCCN-IPI) with score >= 4, at time of diagnosis
• MYC gene rearrangement (by [fluorescent in situ hybridization] FISH)
• MYC overexpression by immunohistochemistry (IHC) (>= 40%) and BLC2 overexpression by IHC (>= 50%) or
• Previously treated transformed low-grade lymphoma to large B cell lymphoma with prior treatment not including an anthracycline
• NOTE: BCL2 and/or BCL6 aberrancy are not required for enrollment, but assessment for rearrangement by FISH and overexpression by IHC are required if there is presence of MYC rearranged by FISH
• Patients must have measurable disease (defined as >= 1.5 cm in diameter) with correlated fluorodeoxyglucose (FDG)-avidity on positron emission tomography (PET) scan with Deauville score of 4 or 5 at time of diagnosis
• Patients must have recovered (i.e., =< grade 1 toxicity) from the reversible effects of prior anticancer therapy, if applicable
• Life expectancy of greater than 3 months
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Absolute neutrophil count >= 1000/mcL (within 14 days prior to registration)
• Platelets >= 75,000/mcl (NOTE: Patients with bone marrow involvement may be eligible with platelets >= 50,000) (within 14 days prior to registration)
• Hemoglobin >= 8 g/dL (within 14 days prior to registration)
• NOTE: Red blood cell (RBC) and platelet transfusion allowed >= 14 days prior to registration
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 14 days prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional ULN (within 14 days prior to registration)
• Creatinine clearance >= 60 mL/min either as estimated by the Cockcroft-Gault equation or based on urine collection (12 or 24 hours) (within 14 days prior to registration)
• Lipase =< 1.5 x ULN with no clinical symptoms suggestive of pancreatitis or cholecystitis (within 14 days prior to registration)
• Amylase =< 1.5 x ULN with no clinical symptoms suggestive of pancreatitis or cholecystitis (within 14 days prior to registration)
• Patients must have blood pressure =< grade 1
• NOTE: Hypertensive patients are permitted if their blood pressure is controlled to =< grade 1 by hypertensive medications
• Female patients must meet at least one of the following criteria:

You may not qualify if…

• Patients with exposure to chemotherapy or immunotherapy =< 30 days prior to starting study treatment are not eligible
• NOTE: Patients may receive at most 1 cycle of R-CHOP, rituximab, or systemic corticosteroids within this timeframe
• NOTE: If patient is registered prior to completion of washout, start date of treatment will need to be confirmed prior to registration
• Patients with prior exposure to a SYK inhibitor are not eligible
• NOTE: Examples of SYK inhibitors include fostamatinib (R788), entospletinib (GS-9973), cerdulatinib (PRT062070), and TAK-659
• Patients with untreated brain metastases or leptomeningeal metastases are not eligible
• Patients with known hypersensitivity (e.g. anaphylactic and anaphylactoid reactions) to TAK-659 or components of R-CHOP are not eligible
• Patients with history of drug-induced pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active pneumonitis on screening imaging are not eligible
• NOTE: A history of radiation pneumonitis in the radiation field (fibrosis) is permitted
• Patients with known hepatitis B surface antigen positive, or known or suspected active hepatitis C infection are not eligible
• Patients who are known to be human immunodeficiency virus (HIV) positive are not eligible
• Patients must not have had autologous stem cell transplant within 6 months prior to registration
• Patients must have not had allogeneic stem cell transplant at any time
• Patients who have received systemic anticancer treatment (including investigational agents) or radiotherapy less than 3 weeks before the first dose of study treatment (=< 5 times half-life for large molecule agents or =< 4 weeks with evidence of disease progression if 5 times half-life is > 4 weeks) are not eligible
• NOTE: Patients may receive R-CHOP cycle 1
• NOTE: If patient is registered prior to completion of washout, start date of treatment will need to be confirmed prior to registration
• Use or consumption of the following substances is not permitted:
• Medications or supplements that are known to be inhibitors of P-gp and/or strong reversible inhibitors of CYP3A within 5 times the inhibitor half-life (if a reasonable half-life estimate is known), or within 7 days (if a reasonable half-life estimate is unknown), before the first dose of study drug. The use of these agents is not permitted during the study
• Medications or supplements that are known to be strong CYP3A mechanism-based inhibitors or strong CYP3A inducers and/or P-gp inducers within 7 days, or within 5 times the inhibitor or inducer half-life (whichever is longer), before the first dose of study drug. The use of these agents is not permitted during the study
• Grapefruit-containing food or beverages within 5 days before the first dose of study drug. Note that grapefruit-containing food and beverages are prohibited during the study
• Patients who have major surgery, per principal investigator (PI) discretion, =< 14 days before the first dose of study drug and those who have not recovered fully from any complications from surgery are not eligible
• Patients who have systemic infection requiring parenteral antibiotic therapy or other serious infection (bacterial, fungal or viral) =< 21 days before the first dose of study drug are not eligible
• NOTE: Patients who are at substantial risk of developing an infection may receive prophylaxis at the start of study treatment per investigator?s discretion
• Patients with an active secondary malignancy that requires treatment are not eligible
• NOTE: Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection and are considered disease-free at the time of registration

Where it is running

• Northwestern University — Chicago, Illinois, United States
• Northwestern Lake Forest Hospital — Lake Forest, Illinois, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.