Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02848911|
Recruitment Status : Suspended
First Posted : July 29, 2016
Last Update Posted : October 16, 2018
|Condition or disease||Intervention/treatment||Phase|
|Leukemia, B-Cell||Drug: AFM11||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||October 2016|
|Estimated Primary Completion Date :||November 2019|
|Estimated Study Completion Date :||November 2019|
IV (intravenous) infusion, dose escalation
Accelerated-titration dose-escalation with 1 patient per dose-level, followed by standard dose-escalation (3 + 3 design), Treatment duration: 2 weeks
- 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
- 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 ]The maximum observed concentration of AFM11 in plasma will be determined.
- 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 ]The area under the concentration versus time curve from time zero to the sampling time will be determined.
- Clinical efficacy of AFM11 in ALL [ Time Frame: Baseline and after treatment (week 3 in step 1 or week 4 in step 2) ]Measured by bone marrow assessment (complete response [CR], complete response with incomplete hematological recovery [CRh], and minimal residual disease [MRD])
- 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 ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02848911
|Kepler Universitätsklinikum Linz|
|Rambam Medical Center|
|Hadassah Medical Center|
|Rabin Medical Center|
|Independent Public Healthcare Municipal Hospital|
|Baranov Republican Hospital|
|Petrozavodsk, Russian Federation|
|First Pavlov State Medical University|
|St. Petersburg, Russian Federation, 197022|
|Almazov NW Federal Medical Research Center|
|St. Petersburg, Russian Federation|