Phase 1/2 Study of TAK-981 in Combination With Rituximab in Patients With Lymphoma
- Conditions
- Relapsed/Refractory CD20-Positive Non-Hodgkin LymphomaMedDRA version: 20.0Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 10005329 - Blood and lymphatic system disordersTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-003946-36-ES
- Lead Sponsor
- Takeda Development Center Americas, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 130
1. Adults =18 years old.
2. For Phase 1 Dose Escalation:aNHL including mantle cell lymphoma and 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, 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 r/r setting; iNHL (including FL of grades 1–3A and marginal zone lymphoma) refractory to rituximab or to any other anti-CD20 monoclonal antibodies, 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.
For Phase 2, the following CD20 positive: 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 received 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 one prior line of therapy must have included a CD20-targeted therapy (Cohort C).
3. Patients must be considered ineligible for, in the opinion of the investigator, or must have refused autologous stem cell transplantation.
4.Eastern Cooperative Oncology Group (ECOG) performance score of =2.
5. Adequate bone marrow function per local laboratory reference range at screening
6. Adequate renal and hepatic function, per local laboratory reference range at screening
7. Left ventricular ejection fraction (LVEF) =40%; as measured by echocardiogram or multiple gated acquisition scan (MUGA).
8. Suitable venous access for safe drug administration and the study-required PK and pharmacodynamic sampling.
9. Have at least 1 bidimensionally measurable lesion per Lugano Classification (>1.5 cm in its largest dimension) by computed tomography (CT). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. In the Phase 2, Stage 1 portion of the study >1 measurable lesions are required, 1 for biopsy, and 1 for response.
10. Willing to consent to 1 mandatory pretreatment and 1 on-treatment skin biopsy during Phase 1. The skin biopsy entry requirement may be discontinued by the sponsor once there is enough pharmacodynamic evidence of target engagement.
11. For patients enrolled in Phase 2, Stage 1, willing to consent to one mandatory pretreatment and 1 on-treatment tumor biopsy. For fresh tumor biopsies, the lesion must be accessible for a low-risk biopsy procedure (those occurring outside the brain, lung/mediastinum, and intra-abdominal, or obtained with endoscopic procedures beyond the stomach or bowel). Outside of Phase 2, Stage 1, paired tumor biopsies are opt
1. CNS lymphoma; active brain or leptomeningeal metastases, as indicated by positive cytology from lumbar puncture or CT scan/magnetic resonance imaging (MRI).
2. Hypersensitivity to TAK-981, rituximab, or any component of the drug product.
3. History of Grade =3 IRR that lead to permanent discontinuation of previous rituximab treatment.
4. Previous participation in the TAK-981-1002 clinical study.
5. Posttransplantation lymphoproliferative disease except relapsed NHL after autologous stem-cell transplantation.
6. Undergone ASCT or treatment with cellular therapy including CAR T within = 3 months of TAK-981 dosing.
7. Prior allogeneic hematopoietic stem-cell transplantation.
8. Lymphomas with leukemic expression.
9. Prior anticancer therapy including chemotherapy, hormonal therapy, or investigational agents within 2 weeks or within at least 5 half-lives before TAK-981 dosing, whichever is shorter. Low dose steroids (oral prednisone or equivalent =20 mg per day), hormonal therapy for prostate cancer or breast cancer (in adjuvant situation), and treatment with bisphosphonates and RANKL (receptor activator of nuclear factor kappa-B ligand) inhibitors are allowed.
10. Major surgery within 14 days before the first dose of study drug and not recovered fully from any complications from surgery.
11. Significant medical diseases or conditions, as assessed by the Investigators and Sponsor that would substantially increase the risk-benefit ratio of participating in the study. This includes but is not limited to acute myocardial infarction or unstable angina within the last 6 months; uncontrolled diabetes mellitus; significant active bacterial, viral or fungal infections; severely immunocompromised state; severe non-compensated hypertension and congestive heart failure New York Heart Association Class III or IV; ongoing symptomatic cardiac arrhythmias of >Grade 2, pulmonary embolism, or symptomatic cerebrovascular events; or any other serious cardiac condition (eg, pericardial effusion or restrictive cardiomyopathy). Chronic atrial fibrillation on stable anticoagulant therapy is allowed.
12. Known chronic hepatitis C and/or positive serology (unless due to vaccination or passive immunization due to Ig therapy) for chronic hepatitis B. Known HIV infection.
13. 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 patient is not on active anticancer therapy as defined in Exclusion Criterion 9.
14. Receipt of any live vaccine within 4 weeks of initiation of study treatment.
15. Active, uncontrolled autoimmune disease requiring >20 mg of prednisone or equivalent, cytotoxics, or biologicals.
16. 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. Patients 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.
17. History of medical or psychiatric illness likely to interfere with the ability to comply with protocol requirements or give informed consent.
18. Patients with baseline prolongation of the Fridericia-correct
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method