Lymphoma, Non-Hodgkin
Conditions
Interventions
Phase 1: TAK-981 10 mg QW
Participants with indolent or aggressive non-Hodgkin lymphoma (NHL) received TAK-981 10 mg, infusion, intravenously (IV), once weekly (QW) on Days 1 and 8 every 21 days in e
Sponsors
Nakayama Ippei
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant Population: a. For Phase 1 Dose Escalation and Japan-specific Lead-in: - Aggressive Non-Hodgkin Lymphoma (aNHL) including mantle cell lymphoma and diffuse large B-cell lymphoma (DLBCL) histologies such as transformed DLBCL from low-grade lymphoma (follicular or others), DLBCL associated with small-cell infiltration in bone marrow, B-cell lymphoma with intermediate features between DLBCL and Burkitt's lymphoma or with intermediate features between DLBCL and Hodgkin lymphoma, follicular lymphoma (FL) grade 3B, and aggressive B-cell lymphoma unclassifiable who must have previously received rituximab, cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine, (Oncovin) and prednisone (R-CHOP) (or equivalent anti-CD20 containing therapy) and 1 additional line of therapy in the relapsed or refractory (r/r) setting. - Indolent non-Hodgkin lymphoma (iNHL) (including FL of grades 1-3A and marginal zone lymphoma) refractory to rituximab or to any other anti-CD20 monoclonal antibody, who have received at least 1 prior systemic therapy for r/r iNHL: - Rituximab or anti-CD20 refractoriness is defined as failure to respond to, or progression during, any previous rituximab/anti-CD20-containing regimen (monotherapy or combined with chemotherapy), or progression within 6 months of the last rituximab or anti-CD20 dose. Note: The minimum qualifying rituximab/anti-CD20 dose is 1 full cycle (that is, weekly*4 doses monotherapy or 1 complete dose if combined with chemotherapy). Prior anti-CD20 antibody or cytotoxic drugs may have been administered as single agents or as components of combination therapies. Each repeated course of the same single-agent or combination is considered an independent regimen. b. For Phase 2, the following confirmed CD20 +: - r/r DLBCL progressed or relapsed after a prior chimeric antigen receptor (CAR) T-cells therapy that has received approval by a health authority for the treatment of DLBCL (Cohort A). - r/r DLBCL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy and has not I prior cellular therapy. At least one prior line of therapy must have included a CD20-targeted therapy (Cohort B). - r/r FL that has progressed or relapsed after at least 2 but no more than 3 prior lines of systemic therapy. At least 1 prior line of therapy must have included a CD20-targeted therapy (Cohort C). 2. Must be considered ineligible in the opinion of the investigator, or refused autologous stem-cell transplantation (ASCT). 3. Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (=) 75.0*10^9/L, Grade 2 thrombocytopenia (platelet count >=50.0*10^9 per liter [/L]) is allowed if it is clearly due to marrow involvement with no evidence of myelodysplastic syndrome or hypoplastic bone marrow if found. Absolute neutrophil count (ANC) >=1.0*10^9/L. Hemoglobin >=85 gram per liter (g/L) (red blood cell [RBC] transfusion allowed >=14 days before assessment). 5. Adequate renal and hepatic function, per local laboratory reference range at screening as follows: - Calculated creatinine clearance >=30 milliliter per minute (mL/min) calculated with Cockcroft-Gault formula. - Potassium levels >=lower limit of normal (LLN). For potassium > upper limit of normal (ULN) discussion with Takeda medical monitor (MM)/designee
Exclusion criteria
Exclusion criteria: 1. Central nervous system lymphoma; active brain or leptomeningeal metastases, as indicated by positive cytology from lumbar puncture or CT scan/magnetic resonance imaging (MRI). 2. History of Grade >=3 infusion-related reaction (IRR) that lead to permanent discontinuation of previous rituximab treatment. 3. Post transplantation lymphoproliferative disease except relapsed NHL after ASCT. 4. Undergone ASCT or treatment with cellular therapy including CAR T within Grade 2, pulmonary embolism, or symptomatic cerebrovascular events, or any other serious cardiac condition (example, pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed. 10. Known chronic hepatitis C and/or positive serology (unless due to vaccination or passive immunization due to immunoglobulin [Ig] therapy) for chronic hepatitis B. Known Human Immunodeficiency Virus (HIV) infection. 11. Second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy. 12. Receipt of any live vaccine within 4 weeks of initiation of study treatment. 13. Active, uncontrolled autoimmune disease requiring >20 mg of prednisone or equivalent, cytotoxics or biologicals. 14. Corticosteroid use within 1 week before the first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. Participants requiring steroids at daily doses >20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for lymphoma control or white blood cell count lowering are not eligible. 15. With baseline prolongation of the QT interval with Fridericia correction method (QTcF) (example, >470 millisecond (ms) for women and >450 ms for men and a history of congenital long QT syndrome, or torsades de pointes). 16. Receiving or requiring the continued use of medications that are known to be strong or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) Time Frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months) Adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. 2.Phase 1: Number of Participants with Grade 3 or Higher TEAEs Time Frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months) AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adverse event which occurred on or after the first dose of study drug and no more than 30 days after the last dose of study drug. A severity grade was evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0, except for Cytokine Release Syndrome (CRS), which was assessed by American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria. 3.Phase 1: Duration of TEAEs Time Frame: From the first dose of study drug through 30 days after the last dose of study drug (up to 42 months) AE means any untoward medical occurrence in a participant administered a pharmaceutical product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product whether or not it is related to the medicinal product. A TEAE was defined as an adve | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.Cmax: Maximum Observed Plasma Concentration for TAK-981 Time Frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple time points (up to 24 hours) post end of infusion; Cycle 2: Days 1 and 8, Pre-infusion and at 10 minutes (mins) post end of infusion (Cycle length = 21 days) 2.Tmax: Time of First Occurrence of the Maximum Plasma Concentration (Cmax) for TAK-981 Time Frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple time points (up to 24 hours) post end of infusion; Cycle 2: Days 1 and 8, Pre-infusion and at 10 mins post end of infusion (Cycle length = 21 days) 3.AUC0-t: Area Under the Plasma Concentration-time Curve from Time 0 to Time t Over the Dosing Interval for TAK-981 Time Frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple time points (up to 24 hours) post end of infusion; Cycle 2: Days 1 and 8, Pre-infusion and at 10 mins post end of infusion (Cycle length = 21 days) 4.AUC0-inf: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981 Time Frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple time points (up to 24 hours) post end of infusion; Cycle 2: Days 1 and 8, Pre-infusion and at 10 mins post end of infusion (Cycle length = 21 days) 5.t1/2z: Terminal Disposition Phase Half-life for TAK-981 Time Frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple time points (up to 24 hours) post end of infusion; Cycle 2: Days 1 and 8, Pre-infusion and at 10 mins post end of infusion (Cycle length = 21 days) 6.CL: Total Clearance After Intravenous Administration for TAK-981 Time Frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple time points (up to 24 hours) post end of infusion; Cycle 2: Days 1 and 8, Pre-infusion and at 10 mins post end of infusion (Cycle length = 21 days) 7.Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981 Time Frame: Cycle 1: Days 1 and 8, pre-infusion and at multiple time points (up to 24 hours) post end of infusion; Cycle 2: Days 1 and 8, P | — |
Countries
Canada, China, France, Germany, Italy, Japan, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Contact for Clinical
Takeda Pharmaceutical Company Limited
Outcome results
None listed