Rituximab and Tafasitamab with Allogeneic NK Cells for relapsed or refractory B-cell NHL
Official title: Phase I Clinical Trial of Rituximab (Rtx) and Tafasitamab in Combination With Allogeneic NK Cells for Treatment of Relapsed/Refractory (r/r) B-cell Non-Hodgkin Lymphoma
Run by Case Comprehensive Cancer Center · NCT07225439 · Data updated 2026-11-12
This trial tests whether giving allogeneic NK cells with Rituximab, Tafasitamab, and IL-2 can help people with relapsed or refractory B-cell non-Hodgkin lymphoma who have tried at least two prior therapies.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 15 (estimated) |
| Sponsor | Case Comprehensive Cancer Center Academic / other |
| Drugs / interventions | prednisone, Tafasitamab, Rituximab, chemotherapy, CAR T, CAR-T, chimeric antigen receptor |
| Locations | 2 sites (Cleveland, Ohio and 1 other locations) |
| Status | Recruiting |
| Started | September 2026 |
| Main results expected | December 2027 |
| Study ends | December 2027 |
| Registry record updated | September 9, 2026 |
| Trial ID | NCT07225439 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Adults (18+) with relapsed or refractory B-cell NHL after at least two prior therapies, including CD19/CD20-directed treatments, with measurable disease.
✕Probably not a fit
Patients with disease progression despite treatment or those unable to tolerate the lymphodepleting regimen or NK cell therapy may not benefit.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This is a Phase 1 interventional study exploring a new cellular therapy approach for relapsed or refractory B-cell NHL. Participants receive lymphodepleting chemotherapy followed by infusions of allogeneic NK cells along with Rituximab, Tafasitamab, and IL-2 to identify a recommended dose and evaluate safety. The study includes adults with a range of B-cell NHL subtypes, including DLBCL, PMBCL, FL, MCL, MZL, CLL/SLL, and others. Eligible patients have measurable disease and have progressed after at least two prior systemic therapies. The trial is conducted at centers in Cleveland, Ohio, with Incyte as a collaborator.
Why it matters
Potential benefit: If successful, participants could experience improved disease control from the NK cell–based combination therapy.
How similar studies have gone: Early studies in NK cell–based approaches show potential, but this exact combination is investigational and its efficacy remains to be demonstrated.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age 18 years or older * Diagnosis of B-cell NHL (indolent and aggressive subtypes) including diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS), high grade B-cell lymphoma (HGBCL), primary mediastinal B-cell lymphoma (PMBCL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL) * Participants must have measurable disease as defined by Lugano 2014 criteria for NHL or iwCLL 2018 criteria for CLL. For NHL, measurable disease is defined as ≥1 measurable lesion (nodal or extra nodal) ≥1.5 cm in longest diameter by CT or PET/CT. For CLL, iwCLL criteria includes: presence of lymphocytosis (e.g., ALC ≥5 × 10⁹/L), lymphadenopathy ≥1.5 cm, and/or disease-related cytopenias (anemia, thrombocytopenia). * Relapsed and/or refractory after two or more lines of systemic therapy, including prior CD19 and/or CD20 directed therapies * For participants who have received a prior CD19 or CD20 directed therapy, the presence of CD19 and/or CD20 expression (by flow cytometry and/or immunohistochemistry) must be demonstrated on a post-treatment relapse biopsy * ECOG Performance Status \</= 2 * Preserved organ function as defined by: Total bilirubin \</= 1.5X upper limit of normal; AST/ALT \</= 2.5 X upper limit of normal; Calculated creatinine clearance \>/= 30mL/min estimated by Cockcroft Gualt formula; cardiac ejection fraction \>/= 45% and no more than mild/trace pericardial effusion on a recent echocardiogram; and adequate pulmonary function with oxygen saturation \>/= 92% on room air. * Participants must have the ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Second active malignancy (other than non-melanoma skin cancer or carcinoma in situ e.g. cervix, bladder, breast) that would confound interpretation of toxicity assessment or limit survival to prevent evaluation of therapy per discretion of principal investigator. Malignancies treated curatively or with hormonal therapy could be included after discussion with the principal investigator * Less than 28 days elapsed between prior treatment with investigational agent(s) and study enrollment * New York Heart Association class III-IV congestive heart failure * Cardiovascular disorders including unstable angina pectoris, clinically significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack, or other ischemic event) within 6 months prior to registration * Known human immunodeficiency virus infection or acquired immunodeficiency syndrome related illness, except well controlled HIV with viral load \<200 copies/mL on antiretroviral therapy * Pregnant or breastfeeding women are excluded from this study because therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants' secondary to treatment of the mother with NK cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study * Morphologic and/or cytogenetic features consistent with diagnosis of myelodysplastic syndrome on the most recent bone marrow biopsy prior to initiation of therapy * Serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive participants will be excluded) * Participants with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease * Active central nervous system or leptomeningeal involvement by lymphoma. Participants with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurological and other adverse events. Participants with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast enhanced MRI imaging for at least 90 days prior to registration * History of active autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of systemic immunosuppressive medications other than low dose steroids \[i.e. maximum of 15mg prednisone equivalent\] within the last 6 months
Where it's running
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Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute
Cleveland, Ohio, United States Recruiting -
Case Comprehensive Cancer Center, University Hospitals Seidman Cancer Center
Cleveland, Ohio, United States Not yet recruiting
Study contacts
- Principal investigator: Paolo Caimi, MD — Case Comprehensive Cancer Center, Cleveland Clinic
- Study coordinator: Paolo Caimi, MD
- Email: caimip@ccf.org
- Phone: (216) 445-4635
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.