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

NCT04074746 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2018-1092NCI-2019-03536
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Adverse events will be summarized by dose.

  Up to 2 years

Secondary Outcomes (8)

• Overall survival

  Up to 2 years

• Event-free survival

  Up to 2 years

• Overall response rate (ORR)

  Up to 2 years

• Complete response (CR) rate

  Up to 2 years

• Partial response (PR) rate

  Up to 2 years

Study Arms (1)

Treatment (AFM13-NK, AFM13)

EXPERIMENTAL

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.

Biological: Anti-CD30/CD16A Monoclonal Antibody AFM13; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Fludarabine Phosphate; Biological: Genetically Engineered Lymphocyte Therapy

Interventions

Anti-CD30/CD16A Monoclonal Antibody AFM13 BIOLOGICAL

Given IV

Also known as: AFM13

Treatment (AFM13-NK, AFM13)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Treatment (AFM13-NK, AFM13)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (AFM13-NK, AFM13)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (AFM13-NK, AFM13)

Genetically Engineered Lymphocyte Therapy BIOLOGICAL

Given AFM13-NK cells IV

Treatment (AFM13-NK, AFM13)

Eligibility Criteria

• Age: 15 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 40186077 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Lymphoma, B-Cell; Mycosis Fungoides; Lymphoma, T-Cell

Interventions

AFM13; Cyclophosphamide; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell, Cutaneous

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Yago L Nieto

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2019
• First Posted: August 30, 2019
• Study Start: July 18, 2020
• Primary Completion: September 22, 2025
• Study Completion: September 22, 2025
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

US (1)