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

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ClinicalTrials.gov Identifier: NCT04074746
Recruitment Status : Recruiting
First Posted : August 30, 2019
Last Update Posted : August 25, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Biological: Anti-CD30/CD16A Monoclonal Antibody AFM13 Drug: Cyclophosphamide Drug: Fludarabine Drug: Fludarabine Phosphate Biological: Genetically Engineered Lymphocyte Therapy Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bispecific Antibody AFM13 Combined With NK Cells for Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas
Actual Study Start Date : July 18, 2020
Estimated Primary Completion Date : April 15, 2023
Estimated Study Completion Date : April 15, 2023


Arm Intervention/treatment
Experimental: 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 -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.
Biological: Anti-CD30/CD16A Monoclonal Antibody AFM13
Given IV
Other Name: AFM13

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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

Drug: Fludarabine
Given IV
Other Name: Fluradosa

Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586

Biological: Genetically Engineered Lymphocyte Therapy
Given AFM13-NK cells IV




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 2 years ]
    Adverse events will be summarized by dose.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Up to 2 years ]
    Distribution will be estimated using Kaplan-Meier method.

  2. Event-free survival [ Time Frame: Up to 2 years ]
    Distribution will be estimated using Kaplan-Meier method.

  3. Overall response rate (ORR) [ Time Frame: Up to 2 years ]
    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.

  4. Complete response (CR) rate [ Time Frame: Up to 2 years ]
    Will be determined by ratio of CRs over number of patients with measurable lesions.

  5. Partial response (PR) rate [ Time Frame: Up to 2 years ]
    Will be determined by ratio of PRs over number of patients with measurable lesions.

  6. Duration of response [ Time Frame: Time of initial response to disease relapse/progression, assessed up to 2 years ]
    The evaluation of the duration of the response will be assessed.

  7. The Persistence of infused donor AFM13-NK cells. [ Time Frame: Up to 2 years ]
    To quantify the persistence of infused donor AFM13-NK cells. Will be summarized with descriptive statistics.

  8. The immune reconstitution studies will assessed. [ Time Frame: Up to 2 years ]
    Will be conducted with the comprehensive immune reconstitution studies and will be summarized with descriptive statistics.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   15 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04074746


Contacts
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Contact: Yago L Nieto 713-792-8750 ynieto@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Yago L. Nieto    713-792-8750      
Principal Investigator: Yago L. Nieto         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Yago L Nieto M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04074746    
Other Study ID Numbers: 2018-1092
NCI-2019-03536 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2018-1092 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: August 30, 2019    Key Record Dates
Last Update Posted: August 25, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mycoses
Lymphoma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Lymphoma, T-Cell
Mycosis Fungoides
Lymphoma, B-Cell
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, T-Cell, Cutaneous
Vidarabine
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Antibodies
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents