Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL

This is an interventional treatment trial for Leukemia, B-Cell focused on measuring acute lymphoblastic leukemia Read More

Inclusion Criteria:

1. 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
2. Patients with CD19+ Philadelphia-chromosome positive ALL who failed or were intolerant to therapy with at least 2 approved tyrosine kinase inhibitors
3. More than 5% blasts in bone marrow
4. 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.
5. Patients of both genders, age ≥ 18

6. Homogenous CD19 expression on leukemic blasts must be confirmed by either:

   1. Prior results from a CD19+ staining or flow cytometry at the most recent available diagnostic bone marrow biopsy or aspirate, or
   2. 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.
7. Eastern Cooperative Oncology Group performance status ≤ 2
8. Life expectancy of at least 3 months
9. Ability to understand the patient information and informed consent form
10. Signed and dated written informed consent

Exclusion Criteria:

1. Autologous HSCT within 3 months prior to start of AFM11 treatment
2. 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.
3. Allogeneic HSCT within 3 months prior to start of AFM11 treatment
4. Prior treatment with blinatumomab or any other CD19 targeting T-cell engager, including CD19 CAR-T cells
5. Treatment with donor-lymphocyte infusions within 4 weeks of start of AFM11 treatment or existing Graft versus Host Disease (GvHD)

6. Known or suspected central nervous system (CNS) involvement:

   1. Evidence for presence of malignant disease, inflammatory lesions, and/or vasculitis on cerebral magnetic resonance imaging (MRI)
   2. Infiltration of the cerebrospinal fluid by malignant B-cells, confirmed by lumbar puncture
7. History of or current relevant CNS pathology as epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis
8. Cancer chemotherapy within 4 weeks prior to start of AFM11 treatment, or at least 4 times the respective half-lives, whichever is longer
9. 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
10. 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
11. Contraindication for any of the concomitant medications
12. 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
13. 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
14. Uncontrolled infections; known bacteremia
15. Any concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the Investigator
16. 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
17. 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
18. Known infection with human immunodeficiency virus or chronic or acute infection with hepatitis B or hepatitis C virus
19. 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.