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

ConditionsNon Hodgkin LymphomaB-cell Non Hodgkin LymphomaDiffuse Large B Cell LymphomaHigh-grade B-cell LymphomaPrimary Mediastinal Large B Cell LymphomaFollicular LymphomaChronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaMarginal Zone LymphomaMantle Cell Lymphoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorPaolo Caimi, MD

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • Allogeneic NK cells

    Drug

    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

    Drug

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

  • Tafasitamab

    Drug

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

  • Interleukin-2

    Drug

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

  • Fludarabine/cyclophosphamide

    Drug

    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).

Treatment groups

15 Participants
are divided into 1 treatment group
Group A: Rtx + Tafasitamab in combination with allogeneic NK CellsExperimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Up to 42 days

Secondary outcomes

1

Incidence of adverse events (AEs)

Time frame
Up to 12 months
2

Timing of adverse events (AEs)

Time frame
Up to 12 months
3

Severity of adverse events (AEs)

AE severity will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0

Time frame
Up to 12 months
4

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.

Time frame
Day 28

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Paolo Caimi, MD

Lead sponsor

Case Comprehensive Cancer Center

Sponsor institution

Incyte Corporation

Collaborator

Source ClinicalTrials.gov
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