Recurrent Anaplastic Large Cell LymphomaPhase 1/2NCT04074746
Modified Immune Cells (AFM13-NK) and A Monoclonal Antibody (AFM13) in Treating Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas
A Phase 1/2 study testing Anti-CD30/CD16A Monoclonal Antibody AFM13, Cyclophosphamide and Fludarabine in people with Recurrent Anaplastic Large Cell Lymphoma and Recurrent B-Cell Non-Hodgkin Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 15 to 75 years
- Conditions the study is for
- Recurrent Anaplastic Large Cell Lymphoma, Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Classic Hodgkin Lymphoma
- What is being tested?
- Anti-CD30/CD16A Monoclonal Antibody AFM13, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jul 2020to 23 Sep 2025
- Phase
- Phase 1/2
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 15 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Bispecific NK Engager AFM13 Combined With NK Cells for Patients With Recurrent of Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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
- 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
- Being tested
- Anti-CD30/CD16A Monoclonal Antibody AFM13, Cyclophosphamide, Fludarabine, Fludarabine Phosphate, Genetically Engineered Lymphocyte Therapy
- Medical subject headings
- Lymphoma, Large-Cell, Anaplastic, Lymphoma, B-Cell, Mycosis Fungoides, Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CD30/CD16A Monoclonal Antibody AFM13Biological
Also called AFM13
Given IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
FludarabineDrug
Also called Fluradosa
Given IV
Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara
Given IV
Genetically Engineered Lymphocyte TherapyBiological
Given AFM13-NK cells IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Anti-CD30/CD16A Monoclonal Antibody AFM13; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Fludarabine Phosphate; Biological: Genetically Engineered Lymphocyte Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerate Dose of AFM13 Umbilical Cord Blood(UCB) Derived Natural Killer(NK) Cells Infused on D=0,D+7,D+14,D+21 for Each Cohort (1x10^6,1x10^7,1x10^8).
Number of Participants who have experienced Dose-limiting toxicity (DLT) during AFM13-NK cell infusions. DLT will be defined as any related grade 3 or greater non- hematologic toxicity that occurs within 28 days of AFM13-NK infusion
Measured: 28 days post AFM13-NK cells on D=0 for each Cohort.
Secondary outcomes (1)
Number of Participants That Achieved Complete Response (CR) Post AFM13-NK Cell Infusions.
Complete Remission requires all of the following:
Complete metabolic response by PET-CT: Score 1-3. Score 1 (no uptake above the background), Score 2 (uptake is less than or equal to the mediastinal blood pool), or Score 3 (uptake is greater than the mediastinal blood pool but less than or equal to the normal liver) with or without a residual mass on 5 point scale or on CT, target nodes/nodal masses must regress to ≤ 1.5 cm in Di.
Lyric Response Criteria (Appendix 2):
Complete Response (CR): PET-CT Scores 1-3 Partial Response (PR): PET-CT Scores 4-5 with reduced uptake compared with baseline.
Progression Disease (PD): PET-CT Scores 4-5 with an increased uptake compared to baseline or new and/or regrowth of measurable lesions.
Measured: Time Frame: 1 year post AFM13-NK cells on D=0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2019
- Study start18 Jul 2020
- Primary completion23 Sep 2025
- Study completion23 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Anaplastic Large Cell LymphomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yago L Nieto, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04074746
- Sponsor's protocol ID
- 2018-1092
- Other IDs
- NCI-2019-03536, 2018-1092
- Status last verified
- Sep 2026
- First submitted
- 17 Jun 2019
- Last updated
- 30 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40186077