Relapsed B-Cell Non-Hodgkin LymphomaPhase 1NCT02106091
Safety Study to Assess AFM11 in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL
A Phase 1 study testing AFM11 in people with Relapsed B-Cell Non-Hodgkin Lymphoma and Refractory B-Cell Non-Hodgkin Lymphoma, run by Affimed GmbH at 9 sites in 4 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed B-Cell Non-Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma
- What is being tested?
- AFM11
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 9 sitesin 4 countries
- Study dates
- Apr 2014to Sep 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- Life expectancy of at least 6 months.
- Ability to understand the patient information and informed consent form.
- Signed and written informed consent
Who cannot join
- 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:
- Peripheral lymphocyte count > 20 × 10^9/L
- Platelet count ≤ 75,000/µL
- Hemoglobin level ≤ 9 g/dL.
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- Known or suspected central nervous system (CNS) involvement.
- History of or current relevant CNS pathology as epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, and/or psychosis.
- Evidence for presence of malignant disease, inflammatory lesions, and/or vasculitis on cerebral MRI.
- 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.
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
Germany5 sites
University Hospital of the Saarland
Homburg/Saar, 66421
University Hospital
Kiel, 24105
University Medical Center of the Johannes Gutenberg University Mainz
Mainz, 55131
University Hospital
Ulm, 89081
University Hospital
Würzburg, 97080
Poland2 sites
SP ZOZ University Hospital Krakow
Krakow, 31501
MTZ Clinical Research
Warsaw, 02106
About this study
Official title: 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).
Read the 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.
- Being tested
- AFM11
- Medical subject headings
- Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AFM11Drug
Accelerated-titration dose-escalation with 1 patient per dose-level, followed by standard dose-escalation (3 + 3 design), Treatment duration: 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| AFM11 | Experimental | IV (intravenous) infusion, dose escalation Receives: Drug: AFM11 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with serious and non-serious adverse events as a measure of safety and tolerability of AFM11.
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.
Measured: From administration of the first dose of study drug and through 30 days after the last dose, up to 8 weeks.
Secondary outcomes (3)
Maximum Tolerated Dose (MTD) of AFM11.
Measured: up to 8 weeks
Pharmacokinetic profile of AFM11 and immunological markers of AFM11 activity.
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.
Measured: 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.
Measure tumor size and activity in FDG-PET and CT-scans.
Measured: Baseline and at week 6.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2014 (estimated)
- Study startApr 2014
- Primary completionAug 2018
- Study completionSep 2018
Why it stopped: Non-favorable risk/benefit profile with studied dosing regimen
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed B-Cell Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Affimed GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02106091
- Sponsor's protocol ID
- AFM11-101
- Other IDs
- 2013-001919-78
- Status last verified
- May 2019
- First submitted
- 1 Apr 2014
- Last updated
- 18 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Topp M, Dlugosz-Danecka M, Skotnicki AB, Salogub G, Viardot A, Klein AK, Hess G, Michel CS, Grosicki S, Gural A, Schwarz SE, Pietzko K, Gartner U, Strassz A, Alland L, Mayer J. Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies. Trials. 2023 Jan 3;24(1):4. doi: 10.1186/s13063-022-06982-7.
PubMed 36597128
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT02106091
- Acronym / sponsor ID
- AFM11-101
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Non-favorable risk/benefit profile with studied dosing regimen
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Affimed GmbHIndustry (pharma, biotech, devices)
- Study start
- Apr 2014
- Primary completion
- Aug 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 8 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AFM11 | Experimental | Drug: AFM11IV (intravenous) infusion, dose escalation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (26 listed)
- 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:
- Known or suspected central nervous system (CNS) involvement.
- Cancer chemotherapy within 4 weeks prior to start of AFM11 treatment, or at least 4 times the respective half-lives, whichever is longer.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AFM11Accelerated-titration dose-escalation with 1 patient per dose-level, followed by standard dose-escalation (3 + 3 design), Treatment duration: 4 weeks. | Drug | AFM11 |
Primary outcome
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.
3 secondary outcomes
Maximum Tolerated Dose (MTD) of AFM11.
Time frame: 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.
Tumor Response.
Time frame: Baseline and at week 6.
Results and safety
The study was stopped early (reason given: Non-favorable risk/benefit profile with studied dosing regimen). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2019.
- Derived from this study: PubMed 36597128Topp M, Dlugosz-Danecka M, Skotnicki AB, Salogub G, Viardot A, Klein AK, Hess G, Michel CS, Grosicki S, Gural A, Schwarz SE, Pietzko K, Gartner U, Strassz A, Alland L, Mayer J. Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies. Trials. 2023 Jan 3;24(1):4. doi: 10.1186/s13063-022-06982-7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AFM11 in people with Relapsed B-Cell Non-Hodgkin Lymphoma and Refractory B-Cell Non-Hodgkin Lymphoma, run by Affimed GmbH at 9 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany, Poland, United States, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Non-favorable risk/benefit profile with studied dosing regimen). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02106091, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2019.