Modified Immune Cells (AFM13-NK) and A Monoclonal Antibody (AFM13) in Treating Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas

NCT ID: NCT04074746

Last Updated: 2025-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-18

Study Completion Date

2025-09-22

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This phase I/II trial studies the side effects and best dose of modified umbilical cord blood immune cells (natural killer \[NK\] cells) combined with the antibody AFM13 (AFM13-NK) and AFM13 alone in treating patients with CD30 positive Hodgkin lymphoma or non-Hodgkin lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as AFM13, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving AFM13 loaded with NK cells followed by AFM13 alone may kill more cancer cells and decrease cancer growth in patients with CD30 positive AFM13-NK Hodgkin and Non-Hodgkin lymphomas.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVE:

I. To establish the safety and recommended phase II dose of umbilical cord blood (CB)-derived natural killer (NK) cells preloaded with the bispecific antibody AFM13 (AFM13-NK), followed by intravenous anti-CD30/CD16A monoclonal antibody AFM13 (AFM13) in patients with refractory/relapsed CD30-positive lymphoid malignancies based on incidence of dose limiting toxicities (DLTs) per dose level. (Phase I) II. To assess the activity of umbilical cord blood (CB)-derived natural killer (NK) cells preloaded with the bispecific antibody AFM13 (AFM13- NK), followed by intravenous AFM13 in patients with refractory/relapsed CD30-positive lymphoid malignancies. based on overall response rate (ORR), complete response (CR) rate and partial response (PR) rate. (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate the duration of response. II. To evaluate the event-free survival (EFS) rate. III. To evaluate the overall survival (OS) time. IV. To quantify the persistence of infused donor CB AFM13-NK cells in the recipient.

V. To conduct comprehensive immune reconstitution studies.

OUTLINE: This is a dose-escalation study of AFM13-NK.

Patients receive standard of care fludarabine intravenously (IV) over 1 hour and standard of care cyclophosphamide IV over 30-60 minutes on days -5 to -3, AFM13-NK IV over 4 hours on day 0, and then AFM13 IV over 4 hours on days 7, 14, and 21.

After completion of study treatment, patients are followed up at 28 days, 8 weeks, 100 and 180 days and then every 3-6 months for 2 years.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Recurrent Anaplastic Large Cell Lymphoma Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Classic Hodgkin Lymphoma Recurrent Mycosis Fungoides Recurrent Peripheral T-Cell Lymphoma, Not Otherwise Specified Refractory Anaplastic Large Cell Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma Refractory Classic Hodgkin Lymphoma Refractory Mycosis Fungoides Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (AFM13-NK, AFM13)

Patients receive standard of care fludarabine IV over 1 hour and standard of care cyclophosphamide IV over 30-60 minutes on days -5 to -3, AFM13-NK IV over 4 hours on day 0, and then AFM13 IV over 4 hours on days 7, 14, and 21.

Group Type EXPERIMENTAL

Anti-CD30/CD16A Monoclonal Antibody AFM13

Intervention Type BIOLOGICAL

Given IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Fludarabine

Intervention Type DRUG

Given IV

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Genetically Engineered Lymphocyte Therapy

Intervention Type BIOLOGICAL

Given AFM13-NK cells IV

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Anti-CD30/CD16A Monoclonal Antibody AFM13

Given IV

Intervention Type BIOLOGICAL

Cyclophosphamide

Given IV

Intervention Type DRUG

Fludarabine

Given IV

Intervention Type DRUG

Fludarabine Phosphate

Given IV

Intervention Type DRUG

Genetically Engineered Lymphocyte Therapy

Given AFM13-NK cells IV

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

AFM13 (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamide Monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Fluradosa 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara SH T 586

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients with a diagnosis of relapsed or refractory classical Hodgkin lymphoma (HL), anaplastic large cell lymphoma (ALCL), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), mycosis fungoides (MF), or B-cell non-Hodgkin lymphoma with a pre-enrollment tumor biopsy positive for CD30 by immunohistochemistry at \>= 1%. Patients with HL, ALCL and MF must be refractory or intolerant to brentuximab vedotin.
* Karnofsky performance status \>= 60%.
* Absolute neutrophil count \>= 500/mm\^3
* Platelet count \>= 50,000/mm\^3
* Serum creatinine clearance \>= 50 ml/min, estimated using the Cockcroft-Gault equation.
* Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN).
* Bilirubin =\< 2 x ULN.
* Alkaline phosphatase (ALP) =\< 2 x ULN.
* Forced expiratory volume in 1 second (FEV1) \>= 50%
* Forced vital capacity (FVC) \>= 50%
* Carbon monoxide diffusing capability test (DLCO) (corrected for hemoglobin \[Hgb\]) \>= 50%
* Left ventricular ejection fraction \>= 40%.
* No uncontrolled arrhythmias or symptomatic cardiac disease.
* If female of child-bearing potential, must not be pregnant or be breastfeeding and required to have a negative urine or serum pregnancy test within 3 days prior to the first dose of study drug.

* Note: Urine pregnancy tests that cannot be confirmed as negative, require a confirmatory negative serum pregnancy test. In addition, females of childbearing potential must agree use of a highly effective method of contraception for the course of the study from 14 days prior to the first dose of study drug until 60 days after the last dose of study drug. Non-childbearing potential is defined as: Postmenopausal: defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, FSH measurements indicating post-menopausal status must be documented in patient's medical history. Permanently sterile: documented permanent sterilization e.g. hysterectomy, bilateral salpingectomy and bilateral oophorectomy. If male, surgically sterile or agrees to use a highly effective method of contraception, 14 days prior to the first dose of study drug until 60 days after the last dose of study drug.

Exclusion Criteria

* Major surgery \< 4 weeks prior to first dose of study drug.
* Any other severe or uncontrolled disease or condition which might increase the risk associated with study participation.
* Any other malignancy known to be active, with the exception of treated cervical intra-epithelial neoplasia and non-melanoma skin cancer.
* Grade \>= 3 non-hematologic toxicity from prior therapy that has not resolved to grade =\< 2.
* Active hepatitis B, either active carrier (hepatitis B surface antigen positive \[HBsAg +\]) or viremic (hepatitis B virus \[HBV\] deoxyribonucleic acid \[DNA\] \>= 10,000 copies/mL, or \>= 2,000 IU/mL), or hepatitis C (detectable viral load by hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] polymerase chain reaction \[PCR\]).
* Active infection requiring parenteral antibiotics.
* Human immunodeficiency virus (HIV) infection.
* Treatment within prior 2 weeks with any anti-cancer agent, investigational or approved.
* Active central nervous system (CNS) involvement (untreated parenchymal brain metastasis or positive cytology of cerebrospinal fluid).
* Life expectancy =\< 6 months.
* Previous treatment with AFM13.
Minimum Eligible Age

15 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Yago L Nieto

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Nieto Y, Banerjee P, Kaur I, Basar R, Li Y, Daher M, Rafei H, Kerbauy LN, Kaplan M, Marin D, Griffin L, Barnett M, Bassett R, Uprety N, Shrestha R, Silva FR, Islam S, Ganesh C, Borneo Z, Ramdial J, Ramirez A, Hosing C, Alousi A, Popat U, Qazilbash M, Ahmed S, Iyer S, Sainz TP, Vega F, Fowlkes NW, Alexis K, Emig M, Harstrick A, Overesch A, Shpall EJ, Rezvani K. Allogeneic NK cells with a bispecific innate cell engager in refractory relapsed lymphoma: a phase 1 trial. Nat Med. 2025 Jun;31(6):1987-1993. doi: 10.1038/s41591-025-03640-8. Epub 2025 Apr 4.

Reference Type DERIVED
PMID: 40186077 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Informed Consent Form

View Document

Related Links

Access external resources that provide additional context or updates about the study.

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

NCI-2019-03536

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-1092

Identifier Type: OTHER

Identifier Source: secondary_id

2018-1092

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.