Recruiting
Phase 1

NK Cells, IL-2, Tafasitamab, Rituximab

Sponsor:

Paolo Caimi, MD

Code:

NCT07225439

Conditions

Non Hodgkin Lymphoma

B-cell Non Hodgkin Lymphoma

Diffuse Large B Cell Lymphoma

High-grade B-cell Lymphoma

Primary Mediastinal Large B Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Allogeneic NK cells

Rituximab

Tafasitamab

Interleukin-2

Fludarabine/cyclophosphamide

Study Details

Brief summary:

This research study is for people who have relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) that has not responded to two or more lines of therapy. The purpose of this study is to identify the recommended dose of allogeneic NK cells in combination with IL-2, Tafasitamab and Rituximab for the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma.

NK cells are an investigational (experimental) treatment which means they are not approved by the Food and Drug Administration (FDA). NK cells are a type of lymphocyte that's part of the body's natural immune system, and they can kill cancer cells by creating pores in the cancer cell membranes and inducing apoptosis (programmed cell death).

Participants in this study will receive lymphodepleting chemotherapy, as well as Allogeneic NK cells, Tafasitamab and Interleukin-2 (IL-2) by an intravenous (IV) infusion. Participants are expected to complete one cycle, and they may be eligible to complete a second cycle of the same regiment if they have stable disease, partial or complete remission at the end of the first cycle. Participants will be in this study for about 12 months.

Conditions

Non Hodgkin Lymphoma

B-cell Non Hodgkin Lymphoma

Diffuse Large B Cell Lymphoma

High-grade B-cell Lymphoma

Primary Mediastinal Large B Cell Lymphoma

Study ID

NCT07225439

Start date

Sep, 2026

Status verified date

Sep, 2026

Completion date

Dec, 2027

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

15 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Rtx + Tafasitamab in combination with allogeneic NK Cells

This arm includes dose escalation for allogeneic NK cells. All other therapies are given according to standard of care. The length of the treatment period is 28 days per cycle. Participants will be expected to complete one cycle and may have the option to complete a second cycle unless there is evidence of disease progression at the end of the first cycle.

Interventions

Allogeneic NK cells

Allogeneic NK cells are given intravenously (IV) weekly for 3 weeks on Days 0, 7, 14.

Dose escalation will be conducted using a Bayesian optimal interval (BOIN) design starting at dose level 1 (500 x 106 cells) and proceeding to dose level 2 (1,000 x 106 cells) if criteria are met.

Rituximab

Rtx is dosed at 375mg/m2 and give once (on Day -5 for Cycle 1 and Day 0 for Cycle 2, if applicable).

Tafasitamab

Tafasitamab is dosed at 12 mg/kg and given intravenously (IV) weekly for 3 weeks on Days 0,7,14).

Interleukin-2

Interleukin-2 is dosed at 5 million IU and given weekly for 3 weeks on Days 0,7,14.

Fludarabine/cyclophosphamide

Fludarabine is dosed at 30 mg/m2/d with dose adjustment for renal function, and cyclophosphamide is dosed at 500 mg/m2/d. These are given on 3 days (Days -5 to -3).

Primary outcome measure

  • Dose limiting toxicity (DLT) [ Time Frame: Up to 42 days ]

Central Contacts and Locations

Central contacts

Paolo Caimi, MD

(216) 445-4635caimip@ccf.org

Locations

Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute

Recruiting

Cleveland, Ohio, United States, 44195

Contacts

Paolo Caimi, MD

caimip@ccf.org

Principal Investigator:

Paolo Caimi, MD

More Information

Sponsor

Paolo Caimi, MD

Last update posted

Sep 9, 2026

Last verified

Sep, 2026

Keywords

  • NK cells
  • Natural Killer cells

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Paolo Caimi, MD on 2026-09-09.