Clinical Trials /

Bispecific Antibody AFM13 Combined With NK Cells for Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas

NCT04074746

Description:

This phase I 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.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • B-Cell Non-Hodgkin Lymphoma
  • Hodgkin Lymphoma
  • Mycosis Fungoides
  • Peripheral T-Cell Lymphoma, NOS
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Modified Immune Cells (AFM13-NK) and A Monoclonal Antibody (AFM13) in Treating Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas
  • Official Title: Bispecific NK Engager (AFM13) Combined With Cord Blood-Derived NK Cells for Refractory Hodgkin and Other CD30+ Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: 2018-1092
  • SECONDARY ID: NCI-2019-03536
  • SECONDARY ID: 2018-1092
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT04074746

Conditions

  • Recurrent Anaplastic Large Cell Lymphoma
  • Recurrent B-Cell Non-Hodgkin Lymphoma
  • Recurrent Classic Hodgkin Lymphoma
  • Recurrent Mycosis Fungoides
  • Recurrent Peripheral T-Cell Lymphoma
  • Refractory Anaplastic Large Cell Lymphoma
  • Refractory B-Cell Non-Hodgkin Lymphoma
  • Refractory Classic Hodgkin Lymphoma
  • Refractory Mycosis Fungoides
  • Refractory Peripheral T-Cell Lymphoma
  • TNFRSF8 Positive

Interventions

DrugSynonymsArms
Anti-CD30/CD16A Monoclonal Antibody AFM13AFM13Treatment (AFM13-NK, AFM13)
Cyclophosphamide(-)-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- 138719Treatment (AFM13-NK, AFM13)
FludarabineFluradosaTreatment (AFM13-NK, AFM13)
Fludarabine Phosphate2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586Treatment (AFM13-NK, AFM13)
Genetically Engineered Lymphocyte TherapyTreatment (AFM13-NK, AFM13)

Purpose

This phase I 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

      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.

      SECONDARY OBJECTIVES:

      I. To assess the overall response rate (ORR), complete response (CR) rate and partial
      response (PR) rate.

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

      VI. 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 -4 to -2, 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (AFM13-NK, AFM13)ExperimentalPatients receive standard of care fludarabine IV over 1 hour and standard of care cyclophosphamide IV over 30-60 minutes on days -4 to -2, AFM13-NK IV over 4 hours on day 0, and then AFM13 IV over 4 hours on days 7, 14, and 21.
  • Anti-CD30/CD16A Monoclonal Antibody AFM13
  • Cyclophosphamide
  • Fludarabine
  • Fludarabine Phosphate
  • Genetically Engineered Lymphocyte Therapy

Eligibility Criteria

        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.

          -  Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate
             transaminase (SGPT) =< 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:

          -  Requirement for systemic corticosteroid therapy < 7 days prior to first dose of study
             drug.

          -  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 4 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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:15 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 2 years
Safety Issue:
Description:Adverse events will be summarized by dose.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Up to 2 years
Safety Issue:
Description:Distribution will be estimated using Kaplan-Meier method.
Measure:Event-free survival
Time Frame:Up to 2 years
Safety Issue:
Description:Distribution will be estimated using Kaplan-Meier method.
Measure:Overall response rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:Will be determined by ratio of responses over number of patients with measurable lesions. Logistic regression will be used to assess the association between ORR and disease and demographic covariates of interest.
Measure:Complete response (CR) rate
Time Frame:Up to 2 years
Safety Issue:
Description:Will be determined by ratio of CRs over number of patients with measurable lesions.
Measure:Partial response (PR) rate
Time Frame:Up to 2 years
Safety Issue:
Description:Will be determined by ratio of PRs over number of patients with measurable lesions.
Measure:Duration of response
Time Frame:Time of initial response to disease relapse/progression, assessed up to 2 years
Safety Issue:
Description:The evaluation of the duration of the response will be assessed.
Measure:The Persistence of infused donor AFM13-NK cells.
Time Frame:Up to 2 years
Safety Issue:
Description:To quantify the persistence of infused donor AFM13-NK cells. Will be summarized with descriptive statistics.
Measure:The immune reconstitution studies will assessed.
Time Frame:Up to 2 years
Safety Issue:
Description:Will be conducted with the comprehensive immune reconstitution studies and will be summarized with descriptive statistics.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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