Safety Study to Assess AFM11 in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL

June 17, 2019 updated by: Affimed GmbH

A Pharmacodynamically-guided, Dose-escalation, Phase I Study to Assess the Safety of AFM11 (Recombinant Antibody Construct Against Human CD19 and CD3) in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL.

The purpose of this study is to determine whether AFM11 is safe and active in the treatment of relapsed and/or refractory Non-Hodgkin Lymphoma (NHL).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

CD19 is present on B-cells from earliest recognizable B-lineage cells during development to B-cell blasts and is lost only upon maturation to plasma cells. Expression of CD19 on B-cells at various development stages makes it an ideal target to treat B-cell associated malignancies.The rationale for the use of AFM11 is based on its ability to bind to both malignant cells via its anti-CD19 domain and to T-cells via its anti-CD3 domains. This results in the formation of the "immunological synapse" and the subsequent T-cell activation on leading to killing of malignant cells.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czechia
      • Prague, Czechia, 11636
        • Charles Hospital Prague
  • Germany
      • Homburg/Saar, Germany, 66421
        • University Hospital of the Saarland
      • Kiel, Germany, 24105
        • University Hospital
      • Mainz, Germany, 55131
        • University Medical Center of the Johannes Gutenberg University Mainz
      • Ulm, Germany, 89081
        • University Hospital
      • Wuerzburg, Germany, 97080
        • University Hospital
  • Poland
      • Krakow, Poland, 31501
        • SP ZOZ University Hospital Krakow
      • Warsaw, Poland, 02106
        • MTZ Clinical Research
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with CD19+, relapsed or refractory histologically (WHO classification) confirmed follicular lymphoma, marginal zone lymphoma, lymphoplasmocytic lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal B-cell lymphoma, or transformed B-cell lymphomas.
  • Patients with either indolent or aggressive NHL.
  • Patients who relapsed or were refractory to the approved standard therapy, which must have included 1 treatment line with rituximab plus chemotherapy, and who are not candidates for bone marrow transplant (including both peripheral blood and hematopoietic stem cell transplants with a curative intent.
  • Measurable disease (at least 1 lesion ≥ 1.5 cm) documented by CT scan.
  • Disease progression requiring therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Life expectancy of at least 6 months.
  • Ability to understand the patient information and informed consent form.
  • Signed and written informed consent

Exclusion Criteria:

  • Total number of B-cells (healthy and malignant combined) in the peripheral blood exceeds the upper physiological limit (as per institutional guidance) of total B-cell counts in healthy individuals.
  • Autologous Hematopoietic stem cell transplant (HSCT) within 12 weeks prior to start of AFM11 treatment.

  • Abnormal hematological laboratory values as defined below:

    1. Peripheral lymphocyte count > 20 × 10^9/L
    2. Platelet count ≤ 75,000/µL
    3. Hemoglobin level ≤ 9 g/dL.

  • Known or suspected central nervous system (CNS) involvement.

    1. History of or current relevant CNS pathology as epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, and/or psychosis.
    2. Evidence for presence of malignant disease, inflammatory lesions, and/or vasculitis on cerebral MRI.
    3. Infiltration of the cerebrospinal fluid by malignant B-cells, confirmed by lumbar puncture.
  • Cancer chemotherapy within 4 weeks prior to start of AFM11 treatment, or at least 4 times the respective half-lives, whichever is longer.
  • Radiotherapy within 4 weeks prior to start of AFM11 treatment.
  • Therapy with antibody, or antibody constructs within 4 weeks prior to start of AFM11 treatment, or at least 4 times the respective half-lives, whichever is longer.
  • Prior treatment with alemtuzumab (Campath®) within 12 weeks prior to start of AFM11 treatment.
  • Treatment with any investigational agent within 4 weeks prior to start of AFM11 treatment, or at least 4 times the respective half-life, whichever is longer.
  • Contraindication for any of the concomitant medications.
  • Abnormal renal or hepatic function as follows: aspartate aminotransferase (AST or serum glutamic oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT or serum glutamic pyruvic transaminase [SGPT]) ≥ 2.5 × upper limit of normal (ULN); total bilirubin ≥ 1.5 × ULN; serum creatinine ≥ 2 × ULN; creatinine clearance < 50 mL/minute.
  • History of malignancy other than B-cell lymphoma within 5 years prior to study entry, with the exception of basal cell carcinoma of the skin or carcinoma in situ of the cervix.
  • Active autoimmune disease requiring systemic immunosuppressive treatment.
  • Uncontrolled infections; known bacteremia.
  • Any concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the Investigator.
  • Regular dose of corticosteroids during the 4 weeks prior to start of AFM11 treatment or anticipated need of continuous corticosteroids exceeding prednisone 20 mg/day or equivalent, or any other immunosuppressive therapy within 4 weeks prior to start of AFM11 treatment.
  • Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B or hepatitis C virus.
  • Pregnant or nursing women or women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least 12 weeks thereafter. Male patients not willing to ensure that during the study and at least 12 weeks thereafter no fathering takes place. Effective methods of contraception include intrauterine device 8(IUD), combined (estrogen- and progesterone-containing) hormonal contraception (oral, vaginal ring or transdermal patch) with an ethinylestradiol dose of at least 30 µg, plus use of male condoms (preferably with spermicides), female condoms, female diaphragm, or cervical cap.
  • Prior treatment with blinatumomab or any other CD19 targeting T-cell engager, including CD19 CAR-T cells.
  • Clinically relevant coronary artery disease (New York Heart Association [NYHA] functional angina classification III/IV), congestive heart failure (NYHA III/IV), or high risk of, or known, uncontrolled arrhythmia.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AFM11
IV (intravenous) infusion, dose escalation
Drug: AFM11
Accelerated-titration dose-escalation with 1 patient per dose-level, followed by standard dose-escalation (3 + 3 design), Treatment duration: 4 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants with serious and non-serious adverse events as a measure of safety and tolerability of AFM11.
Time Frame: From administration of the first dose of study drug and through 30 days after the last dose, up to 8 weeks.
Measure occurence of adverse events until the Final Study Visit and monitor laboratory safety parameters at least once weekly. Assess immunogenicity of AFM11 at end of treatment cycle.
From administration of the first dose of study drug and through 30 days after the last dose, up to 8 weeks.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of AFM11.
Time Frame: up to 8 weeks
up to 8 weeks
Pharmacokinetic profile of AFM11 and immunological markers of AFM11 activity.
Time Frame: Prior to initial dose on Day 1 and at multiple time points during the 4 weeks of treatment until up to 30 days after the last dose.
Concentration of AFM11 in blood samples will measured at different time points during the 4 weeks of treatment and 30 days thereafter to determine concentration-time profiles. Immunological markers like lymphocytes and cytokine levels in serum will be measured at different time points during the 4 weeks of treatment and 30 days thereafter to assess the level of activity resulting from administration of AFM11.
Prior to initial dose on Day 1 and at multiple time points during the 4 weeks of treatment until up to 30 days after the last dose.
Tumor Response.
Time Frame: Baseline and at week 6.
Measure tumor size and activity in FDG-PET and CT-scans.
Baseline and at week 6.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Affimed GmbH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 1, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 8, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 18, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 17, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AFM11-101
  • 2013-001919-78 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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