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

NCT03742258 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: NU 18H02STU00207880P30CA060553NCI-2018-01917
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  Determine the safety and establish the maximum tolerated dose of TAK-659 when combined with R-CHOP in the front-line treatment of high-risk DLBCL using only patients who are evaluable for dose limiting (DLT) toxicities. MTD for TAK-659 will be determined using a 3+3 dose escalation method. The starting dose was 60 mg with possible escalation to 80 mg and 100 mg. Patients may be de-escalated to 40 mg if DLT's were met at dose level 1.

  The first 21 days after the participant received their first dose of TAK-695

Secondary Outcomes (2)

• Overall Response Rate (ORR)

  PET/CT after the completion of Cycle 3

• Progression Free Survival (PFS)

  Up to 18 months

Study Arms (3)

TAK-659 60mg + R-CHOP

EXPERIMENTAL

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 cycle 2, patients also receive spleen tyrosine kinase inhibitor TAK-659 Dose Level 1 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: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Prednisone; Biological: Rituximab; Drug: Spleen Tyrosine Kinase Inhibitor TAK-659; Drug: Vincristine Sulfate

TAK-659 80mg + R-CHOP

EXPERIMENTAL

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 cycle 2, patients also receive spleen tyrosine kinase inhibitor TAK-659 Dose Level 2 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: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Prednisone; Biological: Rituximab; Drug: Spleen Tyrosine Kinase Inhibitor TAK-659; Drug: Vincristine Sulfate

TAK-659 100mg + R-CHOP

EXPERIMENTAL

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 cycle 2, patients also receive spleen tyrosine kinase inhibitor TAK-659 Dose Level 3 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: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Prednisone; Biological: Rituximab; Drug: Spleen Tyrosine Kinase Inhibitor TAK-659; Drug: Vincristine Sulfate

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

TAK-659 100mg + R-CHOP; TAK-659 60mg + R-CHOP; TAK-659 80mg + R-CHOP

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex

TAK-659 100mg + R-CHOP; TAK-659 60mg + R-CHOP; TAK-659 80mg + R-CHOP

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, Servisone, SK-Prednisone

TAK-659 100mg + R-CHOP; TAK-659 60mg + R-CHOP; TAK-659 80mg + R-CHOP

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83

TAK-659 100mg + R-CHOP; TAK-659 60mg + R-CHOP; TAK-659 80mg + R-CHOP

Spleen Tyrosine Kinase Inhibitor TAK-659 DRUG

Given PO

Also known as: Spleen Tyrosine Kinase Inhibitor TAK659, syk Inhibitor TAK-659, syk Inhibitor TAK659, syk-Inhibitor TAK-659, syk-Inhibitor TAK659, TAK-659, TAK659

TAK-659 100mg + R-CHOP; TAK-659 60mg + R-CHOP; TAK-659 80mg + R-CHOP

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

TAK-659 100mg + R-CHOP; TAK-659 60mg + R-CHOP; TAK-659 80mg + R-CHOP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Northwestern Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Cyclophosphamide; Doxorubicin; Prednisone; deltacortene; prednylidene; Rituximab; CT-P10; TAK-659; Vincristine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Dr. Reem Karmali, MD
• Organization: Northwestern University

reem.karmali@northwestern.edu

(312) 695-0711

Study Officials

• Reem Karmali

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2018
• First Posted: November 15, 2018
• Study Start: March 13, 2019
• Primary Completion: March 12, 2021
• Study Completion: February 8, 2024
• Last Updated: June 18, 2025
• Results First Posted: January 29, 2025

Record last verified: 2025-06

Locations

US (2)