Clinical Trials /

AFM13 in Relapsed/Refractory Cutaneous Lymphomas

NCT03192202

Description:

The investigators plan to investigate AFM13 and evaluate its ability to facilitate and redirect the Natural Killer (NK) cells in eliminating CD30-positive lymphoma targets in the skin and, by inference, other organs involved by the lymphoma.

Related Conditions:
  • Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: AFM13 in Relapsed/Refractory Cutaneous Lymphomas
  • Official Title: Clinical and Biological Evaluation of the Novel CD30/CD16A Tetravalent Bispecific Antibody (AFM13) in Relapsed or Refractory CD30-Positive Lymphoma With Cutaneous Presentation: A Biomarker Phase Ib/IIa Study

Clinical Trial IDs

  • ORG STUDY ID: AAAP4461
  • NCT ID: NCT03192202

Conditions

  • Lymphoma, T-Cell, Cutaneous

Interventions

DrugSynonymsArms
AFM13AFM13 recombinant antibodyCohort 1

Purpose

The investigators plan to investigate AFM13 and evaluate its ability to facilitate and redirect the Natural Killer (NK) cells in eliminating CD30-positive lymphoma targets in the skin and, by inference, other organs involved by the lymphoma.

Detailed Description

      This is an open label, Phase Ib/IIa study designed to evaluate the biologic activity of AFM13
      in patients with relapsed or refractory CD30-positive lymphomas with cutaneous involvement.
      Primary cutaneous CD30-positive lymphoproliferative disorders (LPD) represent a spectrum from
      lymphomatoid papulosis (LyP), to primary cutaneous anaplastic large cell lymphoma (C-ALCL),
      to transformed mycosis fungoides (TMF).

      The most indolent form of primary cutaneous CD30-positive LPD is LyP, which is usually well
      controlled with low dose oral methotrexate, but control of the disease frequently requires
      life-long therapy. In contrast, TMF is an aggressive disease which does not have a standard
      of care, as patients are treated with various modalities of care with variable outcomes). The
      spectrum of other CD30-positive lymphomas with cutaneous presentation is very broad and
      involves systemic B and T cell lymphomas with various clinical behaviors.

      Redirecting Natural Killer (NK) cells towards these CD30-positive malignancies through direct
      engagement with AFM13 is expected to induce tumor cell killing through NK cell-mediated and T
      cell-mediated cytotoxicity (i.e., cytotoxic T lymphocytes (CTL)).

      The primary objective of this trial is to study the biologic and immunologic effects induced
      by the administration of various doses of AFM13, when given as a single agent.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1Experimental1.5 mg/kg of AFM13 once weekly for weeks 1-8.
  • AFM13
Cohort 2Experimental1.5 mg/kg of AFM13 three times per week for weeks 1-8.
  • AFM13
Cohort 3Experimental0.5 mg/kg of AFM13 three times per week for weeks 1-2. 7.0 mg/kg of AFM13 once weekly for weeks 3-8.
  • AFM13
Cohort 4Experimental1.5 mg/kg in of AFM13 three times per week for weeks 1-2. 7.0 mg/kg of AFM13 once weekly for weeks 3-8.
  • AFM13
Cohort 5Experimental7.0 mg/kg of AFM13 once weekly for weeks 1-8.
  • AFM13
Cohort 6Experimental4.5 mg/kg of AFM13 three times per week for weeks 1-2. 7.0 mg/kg of AFM13 once weekly for weeks 3-8.
  • AFM13

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥18 years

          -  Histologically confirmed CD30-positive lymphoma with cutaneous involvement

          -  Failure or intolerance to at least one prior therapy for the current disease

          -  Presence of one or more cutaneous lesions (measuring at least 1 cm x 1 cm in size; if
             only one lesion is present it should be up to the investigator discretion to determine
             eligibility)

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤2

          -  Adequate organ and marrow function

          -  Platelets ≥50,000/μL

          -  Absolute neutrophil count ≥ 1,000/μL

          -  Bilirubin < 1.5 x institutional upper limit of normal (ULN) or < 3 x ULN in patients
             with Gilbert's disease or liver involvement

          -  Serum albumin ≥ 2.0 g/dL

          -  Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤2.5 × institutional
             ULN or, in the case of liver involvement by the primary disease AST/ALT ≤ 5 x ULN

          -  Creatinine≤1.5 x institutional ULN or estimated creatinine clearance of ≥45 mL/min by
             the Cockcroft-Gault equation or measured creatinine clearance >45 mL/min

          -  Females of child bearing potential must have a negative serum pregnancy test with 7
             days prior to first dose of treatment. Female patients of childbearing potential and
             all male partners must agree to use double barrier methods of contraception throughout
             the study period and for at least 30 days following investigational product
             discontinuation.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Any cancer-related therapy for the current disease within 2 weeks of screening (all
             supportive care measures are allowed)

          -  Major surgery within 2 weeks prior to first dose of study drug

          -  Evidence of active central nervous system (CNS) involvement

          -  Requirement for systemic immunosuppressive therapy (e.g. Graft-versus-Host Disease
             (GVHD) therapy within 12 weeks before the first dose of study drug)

          -  Uncontrolled concurrent serious illness.

          -  Concurrent malignancy or history of a previous malignancy within 3 years prior to
             first dose of the current study, unless curatively resected basal, squamous cell
             carcinoma of the skin, or cervical carcinoma in situ.

          -  Active infections including hepatitis B carrier status, hepatitis C virus (HCV)
             infection (patients must have a negative Hepatitis B and Hepatitis C viral load at
             screening)

          -  Known HIV-positive status

          -  Any significant medical conditions, laboratory abnormality, or psychiatric illness
             that would exclude the subject from participation or interfere with study treatment,
             monitoring and compliance such as:

          -  unstable angina pectoris, symptomatic congestive heart failure (New York Heart
             Association (NYHA) III or IV), myocardial infarction ≤ 6 months prior to first study
             drug, clinically significant and uncontrolled cardiac arrhythmia (e.g. atrial
             fibrillation/flutter ventricular cardiovascular physiology is allowed),
             cerebrovascular accidents ≤ 6 months before study drug start

          -  severely impaired lung function

          -  Serious, systemic infection requiring treatment ≤7 days before the first dose of study
             drug

          -  Any severe, uncontrolled disease or condition which in the investigator's opinion, may
             put the subject at significant risk, may confound the study results, or impact the
             subject's participation in the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Intratumoral NK-cells and T-cells infiltration into tumors
Time Frame:Up to 2 years
Safety Issue:
Description:Quantified by multiplex Immuno-histochemistry (IHC) using tissue samples

Secondary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:Up to 2 years
Safety Issue:
Description:Incidence of Treatment-Emergent Adverse Events [Safety and Toxicity] broken down by adverse event and CTCAE v4.0 grade of each event.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:The sum of patients with partial responses and complete responses.
Measure:Duration of Response (DOR) after treatment with AFM 13
Time Frame:Up to 2 years
Safety Issue:
Description:The time of initial response until documented tumor progression.
Measure:Progression Free Survival (PFS) after treatment with AFM 13
Time Frame:Up to 2 years
Safety Issue:
Description:The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ahmed Sawas

Trial Keywords

  • Lymphoma
  • Cutaneous Lymphoma
  • cutaneous T-cell lymphoma (CTCL)
  • CD30-Positive Cutaneous Lymphoma
  • T-cell lymphoma
  • PTCL
  • CTCL
  • CD30
  • immunotherapy

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