Clinical Trials /

Phase II Study to Assess AFM13 in Patients With R/R CD30-positive T-cell Lymphoma or Transformed Mycosis Fungoides

NCT04101331

Description:

This is a phase II study to evaluate the antitumor activity and safety of AFM13 given as monotherapy in patients with CD30-positive T-cell lymphoma. The investigational medicinal product AFM13 is a tetravalent bispecific chimeric (anti-human CD30 x anti-human CD16A) recombinant antibody construct which is being developed to treat CD30-positive malignancies. Patients who suffer from peripheral T-cell lymphoma or transformed mycosis fungoides, whose tumor expresses the surface marker CD30, and who have relapsed after an earlier treatment or have refractory disease will be enrolled into this study if all of the study entry criteria are fulfilled. Dependent on their disease type and the magnitude of CD30 expression, study participants will be assigned to one of 3 study cohorts, each cohort receiving the same treatment of weekly AFM13 infusions (a 200mg dose per infusion). The main goal of the study is to assess the efficacy of AFM13 treatment as judged by the rate of objective responses. Further goals are to assess the safety of AFM13 treatment, the immunogenicity of AFM13 (as measured by the potential formation of anti-AFM13 antibodies) and the concentration of AFM13 in the blood. Approx. 1 month after the last dose of AFM13 there will be a final study visit to assess the patients' health status after therapy, followed by quarterly phone contacts to check on their overall health status and long-term survival.

Related Conditions:
  • Mycosis Fungoides
  • Peripheral T-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Study to Assess AFM13 in Patients With R/R CD30-positive T-cell Lymphoma or Transformed Mycosis Fungoides
  • Official Title: A Phase II Open-label Multicenter Study to Assess the Efficacy and Safety of AFM13 in Patients With Relapsed or Refractory CD30-positive Peripheral T-cell Lymphoma or Transformed Mycosis Fungoides (REDIRECT)

Clinical Trial IDs

  • ORG STUDY ID: AFM13-202
  • NCT ID: NCT04101331

Conditions

  • Peripheral T Cell Lymphoma
  • Transformed Mycosis Fungoides

Interventions

DrugSynonymsArms
AFM13Cohort A

Purpose

This is a phase II study to evaluate the antitumor activity and safety of AFM13 given as monotherapy in patients with CD30-positive T-cell lymphoma. The investigational medicinal product AFM13 is a tetravalent bispecific chimeric (anti-human CD30 x anti-human CD16A) recombinant antibody construct which is being developed to treat CD30-positive malignancies. Patients who suffer from peripheral T-cell lymphoma or transformed mycosis fungoides, whose tumor expresses the surface marker CD30, and who have relapsed after an earlier treatment or have refractory disease will be enrolled into this study if all of the study entry criteria are fulfilled. Dependent on their disease type and the magnitude of CD30 expression, study participants will be assigned to one of 3 study cohorts, each cohort receiving the same treatment of weekly AFM13 infusions (a 200mg dose per infusion). The main goal of the study is to assess the efficacy of AFM13 treatment as judged by the rate of objective responses. Further goals are to assess the safety of AFM13 treatment, the immunogenicity of AFM13 (as measured by the potential formation of anti-AFM13 antibodies) and the concentration of AFM13 in the blood. Approx. 1 month after the last dose of AFM13 there will be a final study visit to assess the patients' health status after therapy, followed by quarterly phone contacts to check on their overall health status and long-term survival.

Trial Arms

NameTypeDescriptionInterventions
Cohort AExperimentalPTCL (peripheral T cell lymphoma) patients with CD30 expression ≥10%
  • AFM13
Cohort BExperimentalPTCL (peripheral T cell lymphoma) patients with CD30 expression ≥1% to <10%
  • AFM13
Cohort CExperimentalTMF (transformed mycosis fungoides) patients with CD30 expression ≥1%
  • AFM13

Eligibility Criteria

        Main Inclusion Criteria:

          -  Histologically confirmed CD30-positive PTCL (most subtypes allowed) or TMF per the
             revised World Health Organization 2016 classification (Swerdlow, 2016) by central
             assessment.

          -  Cohorts A and B (PTCL cohorts): measurable by the modified Lugano Classification
             (Cheson, 2014); measurable disease of ≥1.5 cm diameter by computed tomography (CT),
             assessed locally for eligibility. Note: fluorodeoxyglucose (FDG) avid disease by
             positron emission tomography (PET) recommended, if possible.

          -  Cohort C (TMF cohort): measurable by the Olsen Criteria (Olsen, 2011) including at
             least 1 cutaneous lymphoma lesion ≥2 cm in diameter, assessed locally for eligibility.

          -  Patients must have relapsed or refractory disease AND the following:

          -  Cohorts A and B (PTCL): patients must have received at least 1 prior line of systemic
             therapy. For patients with systemic ALCL, patients must have failed or be intolerant
             to brentuximab vedotin [BV]; Adcetris®

          -  Cohort C (TMF): patients must have received at least 1 prior line of systemic therapy;
             and have exhausted systemic therapies with regular approval for their disease

        Main Exclusion Criteria:

          -  Patients with the following subtypes of lymphoma: T-cell prolymphocytic leukemia;
             T-cell large granular lymphocytic leukemia; Chronic lymphoproliferative disorder of NK
             cells; Aggressive NK-cell leukemia; Extranodal NK-/T-cell lymphoma; Indolent T-cell
             lymphoproliferative disorder of the GI tract:

          -  Has had an allogenic tissue hematopoietic cell/solid organ transplant within the last
             3 years. Note: Patients who have had a transplant >3 years ago are eligible as long as
             there are no signs/symptoms of graft versus host disease (GvHD).

          -  Requirement for systemic immunosuppressive therapy, e.g. GvHD therapy, <12 weeks prior
             to the first dose of study drug.

          -  Prior treatment with AFM13
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Antitumor activity of AFM13: Independent Review Committee (IRC)-confirmed objective response rate (ORR)
Time Frame:From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Safety Issue:
Description:Assessed by the modified Lugano Classification (Cheson, 2014) for Cohorts A and B (PTCL) and after at least 8 weeks from the first assessment as assessed by Olsen Criteria (Olsen, 2011) for Cohort C (TMF)

Secondary Outcome Measures

Measure:Antitumor activity of AFM13: Investigator-assessed objective response rate (ORR-2)
Time Frame:From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Safety Issue:
Description:Assessed by the modified Lugano Classification (Cheson, 2014) for Cohorts A and B (PTCL) and after at least 8 weeks from the first assessment as assessed by Olsen Criteria (Olsen, 2011) for Cohort C (TMF)
Measure:Duration of response to AFM13 (DOR)
Time Frame:From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Safety Issue:
Description:Assessed by the modified Lugano Classification (Cheson, 2014) for Cohorts A and B (PTCL) and after at least 8 weeks from the first assessment as assessed by Olsen Criteria (Olsen, 2011) for Cohort C (TMF )
Measure:Safety of AFM13
Time Frame:From screening till final study visit (30-37 days after last dose)
Safety Issue:
Description:Number and frequency of Adverse Events, which includes clinical significant abnormal findings in safety laboratory, vital signs and ECG assessments.
Measure:Pharmacokinetics (PK) of AFM13
Time Frame:During Cycle 1 (each cycle is 56 days)
Safety Issue:
Description:Cmax (maximum measured concentration of the analyte in plasma)
Measure:PK of AFM13
Time Frame:During Cycle 1 (each cycle is 56 days)
Safety Issue:
Description:AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Measure:PK of AFM13
Time Frame:During Cycle 1 (each cycle is 56 days)
Safety Issue:
Description:Vss (Volume of distribution at steady state)
Measure:PK of AFM13
Time Frame:During Cycle 1 (each cycle is 56 days)
Safety Issue:
Description:t1/2 (Terminal half-life)
Measure:Immunogenicity of AFM13
Time Frame:From screening till final study visit (30-37 days after last dose)
Safety Issue:
Description:Maximum change from baseline of anti-drug antibodies (ADA) in blood and their neutralizing potential
Measure:Quality of Life (QoL)
Time Frame:Through study completion, up to 12 months
Safety Issue:
Description:QoL as measured by the European Quality of Life 5-dimensional questionnaire (EQ-5D) for Cohorts A and B; and by Skindex-29 for Cohort C

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Affimed GmbH

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