Leukemia, B-CellPhase 1NCT02848911
Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL
A Phase 1 study testing AFM11 in people with Leukemia, B-Cell, run by Affimed GmbH at 12 sites in 5 countries.
Trial summary
The purpose of the study is to determine the maximum tolerated dose (MTD) in patients with acute lymphoblastic leukemia (ALL) and to determine the safety and tolerability of increasing doses and different infusion times of AFM11 infusion in patients with adult B-precursor ALL Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, B-Cell
- 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
- 17 participants
- Where
- 12 sitesin 5 countries
- Study dates
- Oct 2016to Apr 2019
- 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+ B-precursor Philadelphia-chromosome negative ALL relapsed after at least induction and consolidation or having refractory disease and who are not candidates for bone marrow transplant (including both peripheral blood and hematopoietic stem cell transplant [HSCTs]) with a curative intent at time of screening
- Patients with CD19+ Philadelphia-chromosome positive ALL who failed or were intolerant to therapy with at least 2 approved tyrosine kinase inhibitors
- More than 5% blasts in bone marrow
- In patients with high tumor burden (e.g., more than 50% blasts, or more than 15,000 blasts /µL blood, or elevated lactate dehydrogenase [LDH]) > 2 × upper limit of normal [ULN]), a pre treatment with 10 mg/m2 dexamethasone and 200 mg cyclophosphamide could be administered for up to 5 days.
- Patients of both genders, age ≥ 18
- Homogenous CD19 expression on leukemic blasts must be confirmed by either:
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- Prior results from a CD19+ staining or flow cytometry at the most recent available diagnostic bone marrow biopsy or aspirate, or
- Submission of a recent bone marrow biopsy for staining for CD19 positivity. The results of this testing need to be available prior to start of AFM11 treatment.
- Eastern Cooperative Oncology Group performance status ≤ 2
- Life expectancy of at least 3 months
- Ability to understand the patient information and informed consent form
- Signed and dated written informed consent
Who cannot join
- Autologous HSCT within 3 months prior to start of AFM11 treatment
- Active acute or chronic graft-versus-host disease. All graft-versus-host disease medication should be omitted for at least 4 weeks prior to start of AFM11 treatment.
- Allogeneic HSCT within 3 months prior to start of AFM11 treatment
- Prior treatment with blinatumomab or any other CD19 targeting T-cell engager, including CD19 CAR-T cells
- Treatment with donor-lymphocyte infusions within 4 weeks of start of AFM11 treatment or existing Graft versus Host Disease (GvHD)
- Known or suspected central nervous system (CNS) involvement:
Show all 21Show fewer
- Evidence for presence of malignant disease, inflammatory lesions, and/or vasculitis on cerebral magnetic resonance imaging (MRI)
- Infiltration of the cerebrospinal fluid by malignant B-cells, confirmed by lumbar puncture
- History of or current relevant CNS pathology as epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis
- Cancer chemotherapy within 4 weeks prior to start of AFM11 treatment, or at least 4 times the respective half-lives, whichever is longer
- Therapy with antibody, or antibody constructs within 4 weeks prior to the start of AFM11 treatment, or at least 4 half-lives, whichever is longer
- 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 SGOT) and/or alanine aminotransferase (ALT or SGPT) ≥ 2.5 × ULN; total bilirubin ≥ 1.5 × ULN; serum creatinine ≥ 2 × ULN; creatinine clearance < 50 mL/minute
- History of malignancy other than B-cell lymphoma or B-precursor ALL within 5 years prior to study entry, with the exception of basal cell carcinoma of the skin or carcinoma in situ of the cervix
- 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
- Clinically relevant coronary artery disease (New York Heart Association [NYHA] functional angina classification III/IV), congestive heart failure (NYHA III/IV), high risk of or known uncontrolled arrhythmia
- Regular dose of corticosteroids during the 4 weeks prior to start of AFM11 treatment of this study or anticipated need of corticosteroids exceeding prednisone 20 mg/day or equivalent, or any other immunosuppressive therapy within 4 weeks prior to study entry. Exception is the pre treatment of rapidly progressing disease
- Known infection with human immunodeficiency virus or chronic or acute 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 3 months thereafter. Male patients not willing to ensure that during the study and at least 3 months thereafter no fathering takes place. Effective methods of contraception include intrauterine device (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, a female diaphragm, or a cervical cap.
Trial locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
Austria3 sites
LKH-Universitätsklinikum Graz
Graz
Kepler Universitätsklinikum Linz
Linz
Uniklinikum Salzburg
Salzburg
Israel3 sites
Rambam Medical Center
Haifa
Hadassah Medical Center
Jerusalem
Rabin Medical Center
Petah Tikva
Russia3 sites
Baranov Republican Hospital
Petrozavodsk
First Pavlov State Medical University
Saint Petersburg, 197022
Almazov NW Federal Medical Research Center
Saint Petersburg
Poland2 sites
Independent Public Healthcare Municipal Hospital
Chorzów
University Hospital
Krakow
About this study
Official title: A Phase I Dose-escalation Study to Assess the Safety of AFM11 (CD19 x CD3 TandAb®) in Patients With Relapsed or Refractory Adult B-precursor Acute Lymphoblastic Leukemia
The purpose of the study is to determine the maximum tolerated dose (MTD) in patients with acute lymphoblastic leukemia (ALL) and to determine the safety and tolerability of increasing doses and different infusion times of AFM11 infusion in patients with adult B-precursor ALL
Read the detailed description
Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia characterized by an overproduction of lymphoblasts or lymphocytes in the bone marrow and the peripheral blood; it is frequently accompanied by suppression of normal hematopoiesis. It can spread to the lymph nodes, spleen, liver, the central nervous system (CNS), and other organs (sanctuary sites). Without treatment, ALL usually progresses quickly.
B- and T-cell lymphoblastic leukemia cells express surface antigens that parallel their respective developmental lineages. Precursor B-cell ALL cells typically express CD10, CD19, and CD34 on their surface, along with nuclear terminal deoxynucleotide transferase. About 20% of adult ALL patients have a cytogenetic abnormality that is indistinguishable from the Philadelphia chromosome (Ph1, t(9;22)), according to the National Cancer Institute (NCI).
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. AFM11 has 2 binding sites for CD19 and 2 for CD3, its molecular weight is ~ 105kDa compared to diabodies like blinatumomab with one binding site for each target and a much lower molecular weight ~ 55kDa. In addition, preclinical experiments have shown that AFM11 has about a 100 fold higher affinity to CD3 compared to diabodies and is inducing higher cytotoxicity in vitro in the presence of low effector:target cell ratios. These differences might allow for a shortening of the infusion times and potentially higher clinical efficacy compared to blinatumomab.
- Conditions
- Leukemia, B-Cell
- Being tested
- AFM11
- Keywords
- acute lymphoblastic leukemia
- Medical subject headings
- Leukemia, B-Cell, Precursor Cell Lymphoblastic Leukemia-Lymphoma
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: 2 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 increasing doses and different infusion times of AFM11
Measure of occurence of adverse events (AEs), laboratory testing (chemistry and hematology), physical examination, vital signs, cardiac monitoring, and neurological assessments
Measured: From first administration of continuous infusion over 2 weeks in step 1 (or 4 weeks in step 2) followed by 2 weeks of treatment break
Secondary outcomes (4)
Maximum Plasma Concentration of AFM11 (Cmax)
The maximum observed concentration of AFM11 in plasma will be determined.
Measured: Multiple time points during the 2 weeks of treatment in step 1 and 4 weeks of treatment in step 2
Area Under the Curve (AUC)
The area under the concentration versus time curve from time zero to the sampling time will be determined.
Measured: Prior to initial dose on Day 1 and at multiple time points during the 2 weeks of treatment in step 1 and 4 weeks of treatment in step 2
Clinical efficacy of AFM11 in ALL
Measured by bone marrow assessment (complete response [CR], complete response with incomplete hematological recovery [CRh], and minimal residual disease [MRD])
Measured: Baseline and after treatment (week 3 in step 1 or week 4 in step 2)
Measurement of immunological markers
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 2 weeks of treatment in Step 1 and 4 weeks of treatment in Step 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2016 (estimated)
- Study startOct 2016
- Primary completionSep 2018
- Study completionApr 2019
Why it stopped: Strategic decision was made to terminate the AFM11 development
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 Leukemia, B-CellStudies 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
- 17 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
- NCT02848911
- Sponsor's protocol ID
- AFM11-102
- Status last verified
- Jun 2019
- First submitted
- 18 Jul 2016
- Last updated
- 19 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 19 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose-escalation Study to Assess the Safety of AFM11 (CD19 x CD3 TandAb®) in Patients With Relapsed or Refractory Adult B-precursor Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT02848911
- Acronym / sponsor ID
- AFM11-102
- Conditions
- Leukemia, B-Cell
- Keywords
- acute lymphoblastic leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Strategic decision was made to terminate the AFM11 development
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Affimed GmbHIndustry (pharma, biotech, devices)
- Study start
- Oct 2016 (actual)
- Primary completion
- Sep 2018 (actual)
- Study completion
- Apr 2019 (actual)
- First posted
- 29 Jul 2016 (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 the study is to determine the maximum tolerated dose (MTD) in patients with acute lymphoblastic leukemia (ALL) and to determine the safety and tolerability of increasing doses and different infusion times of AFM11 infusion in patients with adult B-precursor ALL
Detailed description
Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia characterized by an overproduction of lymphoblasts or lymphocytes in the bone marrow and the peripheral blood; it is frequently accompanied by suppression of normal hematopoiesis. It can spread to the lymph nodes, spleen, liver, the central nervous system (CNS), and other organs (sanctuary sites). Without treatment, ALL usually progresses quickly.
B- and T-cell lymphoblastic leukemia cells express surface antigens that parallel their respective developmental lineages. Precursor B-cell ALL cells typically express CD10, CD19, and CD34 on their surface, along with nuclear terminal deoxynucleotide transferase. About 20% of adult ALL patients have a cytogenetic abnormality that is indistinguishable from the Philadelphia chromosome (Ph1, t(9;22)), according to the National Cancer Institute (NCI).
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. AFM11 has 2 binding sites for CD19 and 2 for CD3, its molecular weight is ~ 105kDa compared to diabodies like blinatumomab with one binding site for each target and a much lower molecular weight ~ 55kDa. In addition, preclinical experiments have shown that AFM11 has about a 100 fold higher affinity to CD3 compared to diabodies and is inducing higher cytotoxicity in vitro in the presence of low effector:target cell ratios. These differences might allow for a shortening of the infusion times and potentially higher clinical efficacy compared to blinatumomab.
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 (12 listed)
- Patients with CD19+ B-precursor Philadelphia-chromosome negative ALL relapsed after at least induction and consolidation or having refractory disease and who are not candidates for bone marrow transplant (including both peripheral blood and hematopoietic stem cell transplant [HSCTs]) with a curative intent at time of screening
- Patients with CD19+ Philadelphia-chromosome positive ALL who failed or were intolerant to therapy with at least 2 approved tyrosine kinase inhibitors
- More than 5% blasts in bone marrow
- In patients with high tumor burden (e.g., more than 50% blasts, or more than 15,000 blasts /µL blood, or elevated lactate dehydrogenase [LDH]) > 2 × upper limit of normal [ULN]), a pre treatment with 10 mg/m2 dexamethasone and 200 mg cyclophosphamide could be administered for up to 5 days.
- Patients of both genders, age ≥ 18
Key exclusion criteria (21 listed)
- Autologous HSCT within 3 months prior to start of AFM11 treatment
- Active acute or chronic graft-versus-host disease. All graft-versus-host disease medication should be omitted for at least 4 weeks prior to start of AFM11 treatment.
- Allogeneic HSCT within 3 months prior to start of AFM11 treatment
- Prior treatment with blinatumomab or any other CD19 targeting T-cell engager, including CD19 CAR-T cells
- Treatment with donor-lymphocyte infusions within 4 weeks of start of AFM11 treatment or existing Graft versus Host Disease (GvHD)
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: 2 weeks | Drug | AFM11 |
Primary outcome
Number of participants with serious and non-serious adverse events as a measure of safety and tolerability of increasing doses and different infusion times of AFM11
Time frame: From first administration of continuous infusion over 2 weeks in step 1 (or 4 weeks in step 2) followed by 2 weeks of treatment break
Measure of occurence of adverse events (AEs), laboratory testing (chemistry and hematology), physical examination, vital signs, cardiac monitoring, and neurological assessments
4 secondary outcomes
Maximum Plasma Concentration of AFM11 (Cmax)
Time frame: Multiple time points during the 2 weeks of treatment in step 1 and 4 weeks of treatment in step 2
Area Under the Curve (AUC)
Time frame: Prior to initial dose on Day 1 and at multiple time points during the 2 weeks of treatment in step 1 and 4 weeks of treatment in step 2
Clinical efficacy of AFM11 in ALL
Time frame: Baseline and after treatment (week 3 in step 1 or week 4 in step 2)
Measurement of immunological markers
Time frame: Prior to initial dose on Day 1 and at multiple time points during the 2 weeks of treatment in Step 1 and 4 weeks of treatment in Step 2
Results and safety
The study was stopped early (reason given: Strategic decision was made to terminate the AFM11 development). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 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.
12 sites in 5 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 Leukemia, B-Cell, run by Affimed GmbH at 12 sites in 5 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 12 inclusion and 21 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 19 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 12 sites in Austria, Israel, Russia, Poland, 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: Strategic decision was made to terminate the AFM11 development). 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 increasing doses and different infusion times of AFM11 (time frame: From first administration of continuous infusion over 2 weeks in step 1 (or 4 weeks in step 2) followed by 2 weeks of treatment break). 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 NCT02848911, 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 19 Jun 2019.