Non Hodgkin LymphomaPhase 1NCT07225439

Rituximab (Rtx) + Tafasitamab in Combination With Allogeneic NK Cells for Treatment of Relapsed/Refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL)

A Phase 1 study testing Allogeneic NK cells, Rituximab and Tafasitamab in people with Non Hodgkin Lymphoma and B-cell Non Hodgkin Lymphoma, run by Paolo Caimi, MD at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Non Hodgkin Lymphoma, B-cell Non Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma
What is being tested?: Allogeneic NK cells, Rituximab and Tafasitamab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 2 sitesUnited States
Study dates: Sep 2026to Dec 2027
Phase: Phase 1
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 11Show fewer

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

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Paolo Caimi, MD contact

(216) 445-4635

caimip@ccf.org

United States2 sites, 2 recruiting

Case Comprehensive Cancer Center, University Hospitals Seidman Cancer Center
Cleveland, Ohio, 44106
Changchun (George) Deng, Changchun.Deng@UHhospitals.org
Changchun (George) Deng, MD
Not yet recruiting
Case Comprehensive Cancer Center, Cleveland Clinic Foundation Taussig Cancer Institute
Cleveland, Ohio, 44195
Paolo Caimi, MD, caimip@ccf.org
Paolo Caimi, MD
Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

More than 80,000 cases of non-Hodgkin lymphoma (NHL) are diagnosed each year in the United States (US), with nearly 20,000 people dying from this group of diseases annually. There are several subgroups of NHL, with the B cell lymphomas being much more common than T-cell lymphomas. B cell lymphomas include multiple different diseases, including some that are more aggressive (like diffuse large B cell lymphoma (DLBCL) and others), as well as those with a slower progression (i.e. indolent lymphomas like follicular lymphoma (FL)). Over the past 20 years, there have been advances in the treatment of most NHL subtypes. However, disease recurrence continues to be frequent and happens in more than a third of people with DLBCL and in most people with indolent lymphomas. A treatment called anti CD19 chimeric antigen receptor T-cell therapies (CAR T-cell) have helped to treat relapsed and primary refractory lymphomas. However, CAR-T cells therapies are limited by the cost and logistics of manufacture. Additionally, relapses are common (40-60%) in people treated with CAR-T cells, and people who experience these relapses have poor survival outcomes.

While CAR-T cells still receive a lot of attention, there is a growing interest in using other strategies including NK cells combined with monoclonal antibodies or molecules developed to activate NK cells against tumors. NK cells are lymphocytes, a type of immune cell, that can naturally fight cancer cells. They are important in fighting cancer and can do so without needing to recognize specific cell markers. Allogeneic, non-HLA-matched NK cells have been found to be safe and not associated with the development of graft-versus-host disease. It is still important to improve the manufacture, application, and efficacy of NK cell therapy. Breakthroughs in ex vivo NK cell expansion have allowed for large doses to be made, which may address some of these limitations.

This study uses a "universal donor" of ex vivo expanded NK cell product that is made at a lab at Case Western Reserve University. These NK cells are "experimental," meaning that they are not approved by the Food and Drug Administration (FDA). Participants in this study will receive these NK cells in addition to other standard cancer treatments for NHL.

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, Follicular Lymphoma
Being tested: Allogeneic NK cells, Rituximab, Tafasitamab, Interleukin-2, Fludarabine/cyclophosphamide
Keywords: NK cells, Natural Killer cells
Medical subject headings: Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Allogeneic NK cellsDrug
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.
RituximabDrug
Also called Rtx
Rtx is dosed at 375mg/m2 and give once (on Day -5 for Cycle 1 and Day 0 for Cycle 2, if applicable).
TafasitamabDrug
Tafasitamab is dosed at 12 mg/kg and given intravenously (IV) weekly for 3 weeks on Days 0,7,14).
Interleukin-2Drug
Interleukin-2 is dosed at 5 million IU and given weekly for 3 weeks on Days 0,7,14.
Fludarabine/cyclophosphamideDrug
Also called Flu/Cy
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).

Study groups in NCT07225439
Study group	Role	What they receive
Rtx + Tafasitamab in combination with allogeneic NK Cells	Experimental	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. Receives: Drug: Allogeneic NK cells; Drug: Rituximab; Drug: Tafasitamab; Drug: Interleukin-2; Drug: Fludarabine/cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

Dose limiting toxicity (DLT)
Non hematologic AEs will be measured during cycle 1 (first 28 days) and hematologic AEs will be measured during the first 42 days for all dose levels. DLTs are graded for severity by the Common Terminology Criteria for Adverse Events v5.0 (CTCAEv5.0) criteria.
Measured: Up to 42 days

Secondary outcomes (9)

Incidence of adverse events (AEs)
Measured: Up to 12 months
Timing of adverse events (AEs)
Measured: Up to 12 months
Severity of adverse events (AEs)
AE severity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0
Measured: Up to 12 months
Complete response (CR) rate
CR is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy and measured according to the 2014 Lugano Response for Malignant Lymphoma criteria.
Measured: Day 28
Complete response (CR) rate
CR is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy and measured according to the 2014 Lugano Response for Malignant Lymphoma criteria.
Measured: Day 100
Overall response rate (ORR)
ORR is defined as the rate of participants who had CR and partial response (PR). CR is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy and measured according to the 2014 Lugano Response for Malignant Lymphoma criteria. PR is defined as not meeting criteria for CR but having an improvement in symptom criteria specified by the 2014 Lugano Response for Malignant Lymphoma criteria.
Measured: Day 28
Overall response rate (ORR)
ORR is defined as the rate of participants who had CR and partial response (PR). CR is defined as complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy and measured according to the 2014 Lugano Response for Malignant Lymphoma criteria. PR is defined as not meeting criteria for CR but having an improvement in symptom criteria specified by the 2014 Lugano Response for Malignant Lymphoma criteria.
Measured: Day 100
Overall survival (OS)
OS is defined as the time from infusion until death from any cause, or until last contact if alive
Measured: Up to 12 months
Event-free survival (EFS)
EFS is defined as the time from infusion until the first occurrence of an event (relapse, progression, or death from any cause), or until last contact if no event occurs.
Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2026Dec 2027

First posted6 Nov 2025
Study startSep 2026 (estimated)
Primary completionDec 2027 (estimated)
Study completionDec 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (13)Papers the sponsor has linked to this study.
Other trials for Non Hodgkin LymphomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 15 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07225439
Sponsor's protocol ID: CASE1425
Status last verified: Sep 2026
First submitted: 4 Nov 2025
Last updated: 9 Sep 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Non-Hodgkin Lymphoma - Cancer Stat Facts [Internet]. [cited 2024 Jul 31]. Available from: https://seer.cancer.gov/statfacts/html/nhl.html
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795.
PubMed 11807147
Duell J, Maddocks KJ, Gonzalez-Barca E, Jurczak W, Liberati AM, De Vos S, Nagy Z, Obr A, Gaidano G, Abrisqueta P, Kalakonda N, Andre M, Dreyling M, Menne T, Tournilhac O, Augustin M, Rosenwald A, Dirnberger-Hertweck M, Weirather J, Ambarkhane S, Salles G. Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Haematologica. 2021 Sep 1;106(9):2417-2426. doi: 10.3324/haematol.2020.275958.
PubMed 34196165
Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, Kim TM, Kim WS, Ozcan M, Hirata J, Penuel E, Paulson JN, Cheng J, Ku G, Matasar MJ. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020 Jan 10;38(2):155-165. doi: 10.1200/JCO.19.00172. Epub 2019 Nov 6.
PubMed 31693429
Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800. doi: 10.1016/S1470-2045(21)00139-X. Epub 2021 May 11.
PubMed 33989558
Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR, Hillmen P, Stephens DM, Ghia P, Barrientos JC, Pagel JM, Woyach J, Johnson D, Huang J, Wang X, Kaptein A, Lannutti BJ, Covey T, Fardis M, McGreivy J, Hamdy A, Rothbaum W, Izumi R, Diacovo TG, Johnson AJ, Furman RR. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):323-32. doi: 10.1056/NEJMoa1509981. Epub 2015 Dec 7.
PubMed 26641137
Eichhorst B, Niemann CU, Kater AP, Furstenau M, von Tresckow J, Zhang C, Robrecht S, Gregor M, Juliusson G, Thornton P, Staber PB, Tadmor T, Lindstrom V, da Cunha-Bang C, Schneider C, Poulsen CB, Illmer T, Schottker B, Nosslinger T, Janssens A, Christiansen I, Baumann M, Frederiksen H, van der Klift M, Jager U, Leys MBL, Hoogendoorn M, Lotfi K, Hebart H, Gaska T, Koene H, Enggaard L, Goede J, Regelink JC, Widmer A, Simon F, De Silva N, Fink AM, Bahlo J, Fischer K, Wendtner CM, Kreuzer KA, Ritgen M, Bruggemann M, Tausch E, Levin MD, van Oers M, Geisler C, Stilgenbauer S, Hallek M; GCLLSG, the HOVON and Nordic CLL Study Groups, the SAKK, the Israeli CLL Association, and Cancer Trials Ireland. First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia. N Engl J Med. 2023 May 11;388(19):1739-1754. doi: 10.1056/NEJMoa2213093.
PubMed 37163621
ASCO Daily News [Internet]. [cited 2024 Jul 31]. How Do CAR T Cells Fit Into the Evolving Non-Hodgkin Lymphoma Treatment Landscape? Available from: https://dailynews.ascopubs.org/doi/10.1200/ADN.24.201682
Di Blasi R, Le Gouill S, Bachy E, Cartron G, Beauvais D, Le Bras F, Gros FX, Choquet S, Bories P, Feugier P, Casasnovas O, Bay JO, Mohty M, Joris M, Gastinne T, Sesques P, Tudesq JJ, Vercellino L, Morschhauser F, Gat E, Broussais F, Houot R, Thieblemont C. Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T analysis. Blood. 2022 Dec 15;140(24):2584-2593. doi: 10.1182/blood.2022016945.
PubMed 36122385
Gu T, Zhu M, Huang H, Hu Y. Relapse after CAR-T cell therapy in B-cell malignancies: challenges and future approaches. J Zhejiang Univ Sci B. 2022 Oct 15;23(10):793-811. doi: 10.1631/jzus.B2200256.
PubMed 36226535
Derigs P, Bethge WA, Kramer I, Holtick U, von Tresckow B, Ayuk F, Penack O, Vucinic V, von Bonin M, Baldus C, Mougiakakos D, Wulf G, Schnetzke U, Stelljes M, Fante M, Schroers R, Kroeger N, Dreger P; German Lymphoma Alliance and the German Registry for Stem Cell Transplantation. Long-Term Survivors after Failure of Chimeric Antigen Receptor T Cell Therapy for Large B Cell Lymphoma: A Role for Allogeneic Hematopoietic Cell Transplantation? A German Lymphoma Alliance and German Registry for Stem Cell Transplantation Analysis. Transplant Cell Ther. 2023 Dec;29(12):750-756. doi: 10.1016/j.jtct.2023.09.008. Epub 2023 Sep 13.
PubMed 37709204
Grossenbacher SK, Aguilar EG, Murphy WJ. Leveraging natural killer cells for cancer immunotherapy. Immunotherapy. 2017 May;9(6):487-497. doi: 10.2217/imt-2017-0013.
PubMed 28472904
Olson JA, Leveson-Gower DB, Gill S, Baker J, Beilhack A, Negrin RS. NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects. Blood. 2010 May 27;115(21):4293-301. doi: 10.1182/blood-2009-05-222190. Epub 2010 Mar 16.
PubMed 20233969

Interested in taking part?

Paolo Caimi, MD

(216) 445-4635

caimip@ccf.org

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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All Non Hodgkin Lymphoma trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT07225439
Acronym / sponsor ID: CASE1425
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, Follicular Lymphoma
Keywords: NK cells, Natural Killer cells
Phase: Phase 1
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 15 participants (estimated)
Lead sponsor: Paolo Caimi, MDUniversity, hospital or other
Collaborators: Incyte Corporation
Study start: Sep 2026 (estimated)
Primary completion: Dec 2027 (estimated)
Study completion: Dec 2027 (estimated)
First posted: 6 Nov 2025 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Rtx + Tafasitamab in combination with allogeneic NK Cells	Experimental	Drug: Allogeneic NK cells, Drug: Rituximab, Drug: Tafasitamab, Drug: Interleukin-2, Drug: Fludarabine/cyclophosphamideThis 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Allogeneic NK cellsAllogeneic 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.	Drug	Rtx + Tafasitamab in combination with allogeneic NK Cells
RituximabAlso: RtxRtx is dosed at 375mg/m2 and give once (on Day -5 for Cycle 1 and Day 0 for Cycle 2, if applicable).	Drug	Rtx + Tafasitamab in combination with allogeneic NK Cells
TafasitamabTafasitamab is dosed at 12 mg/kg and given intravenously (IV) weekly for 3 weeks on Days 0,7,14).	Drug	Rtx + Tafasitamab in combination with allogeneic NK Cells
Interleukin-2Interleukin-2 is dosed at 5 million IU and given weekly for 3 weeks on Days 0,7,14.	Drug	Rtx + Tafasitamab in combination with allogeneic NK Cells
Fludarabine/cyclophosphamideAlso: Flu/CyFludarabine 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).	Drug	Rtx + Tafasitamab in combination with allogeneic NK Cells

Primary outcome

Dose limiting toxicity (DLT)
Time frame: Up to 42 days
Non hematologic AEs will be measured during cycle 1 (first 28 days) and hematologic AEs will be measured during the first 42 days for all dose levels. DLTs are graded for severity by the Common Terminology Criteria for Adverse Events v5.0 (CTCAEv5.0) criteria.

9 secondary outcomes

Incidence of adverse events (AEs)
Time frame: Up to 12 months
Timing of adverse events (AEs)
Time frame: Up to 12 months
Severity of adverse events (AEs)
Time frame: Up to 12 months
Complete response (CR) rate
Time frame: Day 28
Complete response (CR) rate
Time frame: Day 100
Overall response rate (ORR)
Time frame: Day 28
Overall response rate (ORR)
Time frame: Day 100
Overall survival (OS)
Time frame: Up to 12 months
Event-free survival (EFS)
Time frame: Up to 12 months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
BackgroundNon-Hodgkin Lymphoma - Cancer Stat Facts [Internet]. [cited 2024 Jul 31]. Available from: https://seer.cancer.gov/statfacts/html/nhl.html
Background: PubMed 11807147Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795.
Background: PubMed 34196165Duell J, Maddocks KJ, Gonzalez-Barca E, Jurczak W, Liberati AM, De Vos S, Nagy Z, Obr A, Gaidano G, Abrisqueta P, Kalakonda N, Andre M, Dreyling M, Menne T, Tournilhac O, Augustin M, Rosenwald A, Dirnberger-Hertweck M, Weirather J, Ambarkhane S, Salles G. Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Haematologica. 2021 Sep 1;106(9):2417-2426. doi: 10.3324/haematol.2020.275958.
Background: PubMed 31693429Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, Kim TM, Kim WS, Ozcan M, Hirata J, Penuel E, Paulson JN, Cheng J, Ku G, Matasar MJ. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020 Jan 10;38(2):155-165. doi: 10.1200/JCO.19.00172. Epub 2019 Nov 6.
Background: PubMed 33989558Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800. doi: 10.1016/S1470-2045(21)00139-X. Epub 2021 May 11.
Background: PubMed 26641137Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR, Hillmen P, Stephens DM, Ghia P, Barrientos JC, Pagel JM, Woyach J, Johnson D, Huang J, Wang X, Kaptein A, Lannutti BJ, Covey T, Fardis M, McGreivy J, Hamdy A, Rothbaum W, Izumi R, Diacovo TG, Johnson AJ, Furman RR. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):323-32. doi: 10.1056/NEJMoa1509981. Epub 2015 Dec 7.
Background: PubMed 37163621Eichhorst B, Niemann CU, Kater AP, Furstenau M, von Tresckow J, Zhang C, Robrecht S, Gregor M, Juliusson G, Thornton P, Staber PB, Tadmor T, Lindstrom V, da Cunha-Bang C, Schneider C, Poulsen CB, Illmer T, Schottker B, Nosslinger T, Janssens A, Christiansen I, Baumann M, Frederiksen H, van der Klift M, Jager U, Leys MBL, Hoogendoorn M, Lotfi K, Hebart H, Gaska T, Koene H, Enggaard L, Goede J, Regelink JC, Widmer A, Simon F, De Silva N, Fink AM, Bahlo J, Fischer K, Wendtner CM, Kreuzer KA, Ritgen M, Bruggemann M, Tausch E, Levin MD, van Oers M, Geisler C, Stilgenbauer S, Hallek M; GCLLSG, the HOVON and Nordic CLL Study Groups, the SAKK, the Israeli CLL Association, and Cancer Trials Ireland. First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia. N Engl J Med. 2023 May 11;388(19):1739-1754. doi: 10.1056/NEJMoa2213093.
BackgroundASCO Daily News [Internet]. [cited 2024 Jul 31]. How Do CAR T Cells Fit Into the Evolving Non-Hodgkin Lymphoma Treatment Landscape? Available from: https://dailynews.ascopubs.org/doi/10.1200/ADN.24.201682
Background: PubMed 36122385Di Blasi R, Le Gouill S, Bachy E, Cartron G, Beauvais D, Le Bras F, Gros FX, Choquet S, Bories P, Feugier P, Casasnovas O, Bay JO, Mohty M, Joris M, Gastinne T, Sesques P, Tudesq JJ, Vercellino L, Morschhauser F, Gat E, Broussais F, Houot R, Thieblemont C. Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T analysis. Blood. 2022 Dec 15;140(24):2584-2593. doi: 10.1182/blood.2022016945.
Background: PubMed 36226535Gu T, Zhu M, Huang H, Hu Y. Relapse after CAR-T cell therapy in B-cell malignancies: challenges and future approaches. J Zhejiang Univ Sci B. 2022 Oct 15;23(10):793-811. doi: 10.1631/jzus.B2200256.
Background: PubMed 37709204Derigs P, Bethge WA, Kramer I, Holtick U, von Tresckow B, Ayuk F, Penack O, Vucinic V, von Bonin M, Baldus C, Mougiakakos D, Wulf G, Schnetzke U, Stelljes M, Fante M, Schroers R, Kroeger N, Dreger P; German Lymphoma Alliance and the German Registry for Stem Cell Transplantation. Long-Term Survivors after Failure of Chimeric Antigen Receptor T Cell Therapy for Large B Cell Lymphoma: A Role for Allogeneic Hematopoietic Cell Transplantation? A German Lymphoma Alliance and German Registry for Stem Cell Transplantation Analysis. Transplant Cell Ther. 2023 Dec;29(12):750-756. doi: 10.1016/j.jtct.2023.09.008. Epub 2023 Sep 13.
Background: PubMed 28472904Grossenbacher SK, Aguilar EG, Murphy WJ. Leveraging natural killer cells for cancer immunotherapy. Immunotherapy. 2017 May;9(6):487-497. doi: 10.2217/imt-2017-0013.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Paolo Caimi, MD contact

(216) 445-4635

caimip@ccf.org

Paolo Caimi, MD principal investigator

Case Comprehensive Cancer Center, Cleveland Clinic

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allogeneic NK cells, Rituximab and Tafasitamab in people with Non Hodgkin Lymphoma and B-cell Non Hodgkin Lymphoma, run by Paolo Caimi, MD at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Paolo Caimi, MD ((216) 445-4635, caimip@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity (DLT) (time frame: Up to 42 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07225439, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.