BI 836858 Dose Escalation in Patients With Refractory or Relapsed Acute Myeloid Leukemia and in Patients With AML in Complete Remission With High Risk to Relapse

A Phase I, Open-label, Cohort Dose Escalation Trial With BI 836858 in Patients With Refractory or Relapsed Acute Myeloid Leukemia and Patients With Acute Myeloid Leukemia in Complete Remission With High Risk to Relapse.

Patients with acute myeloid leukemia who experience a relapse after at least one prior regimen may be enrolled in this trial. In addition, acute myeloid leukemia patients who are in complete remission with high risk to relapse may be eligible for this trial. The trial will examine whether monotherapy with BI 836858 is safe and tolerable at escalating dose levels.

Inclusion criteria:

1. Diagnosis of relapsed or refractory AML with at least one prior treatment for acute myeloid leukemia and patients with diagnosis of acute myeloid leukemia in complete remission with high risk to relapse.
2. Expression of CD33 on more than 30% of bone marrow blasts at screening for patients with refractory or relapsed acute myeloid leukemia is required. CD33 positive expression of bone marrow blasts at the time of initial acute myeloid leukemia diagnosis is sufficient for those patients in complete remission with high risk to relapse.
3. Eastern Cooperative Oncology Group Performance Status 0, 1 or 2
4. Age 18 years or older
5. Written informed consent which is consistent with International Conference on Harmonization, Good Clinical Practice (ICH-GCP) guidelines and local legislation.

Exclusion criteria:

1. Patients with acute promyelocytic leukemia according to WHO definition.

2. Patients with refractory or relapsed acute myeloid leukemia > 5.000 blasts in the peripheral blood.

3. Anti-leukemia therapy within two weeks before first treatment with BI 836858, 4 weeks for biologics. Parallel treatment with Hydroxyurea ia allowed with refractory or relapsed acute myeloid leukemia patients.

4. Allogeneic stem cell transplantation within the last 28 days before first treatment with graft versus host disease requiring more than 20 mg of steroids per day. Steroid dosage must be stable within two weeks prior to start of treatment.

5. Patients who are candidates for allogeneic stem cell transplantation (for patients with refractory or relapsed acute myeloid leukemia).

6. Second malignancy currently requiring active therapy.

7. Symptomatic central nervous system involvement

8. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (ULN), or AST or ALT greater than 5 times the ULN for those with Gilbert syndrome.

9. Prothrombin time (PT) >1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin)

10. Bilirubin greater than 1.5 mg/dl (>26 µmol/L) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert syndrome, or hemolysis.

11. Serum creatinine greater than 2.0 mg/dl

12. Known human immunodeficiency virus (HIV) infection or active hepatitis B virus or hepatitis C virus infection.

13. Concomitant intercurrent illness, or any condition which in the opinion of the Investigator, would compromise safe participation in the study, e.g. active severe infection, unstable angina pectoris, new onset of exacerbation of a cardiac arrhythmia

14. Psychiatric illness or social situation that would limit compliance with trial requirements

15. Concomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drug

16. Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for 6 months after the last administration of BI 836858

17. Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second effective method of contraception during the trial and for 6 months after the last administration of BI 836858

18. Pregnant or nursing female patients

19. Treatment with another investigational agent under the following conditions:

    1. Within two weeks (4 weeks for biologics or 5 half-lives, whichever is longer) of first administration of BI 836858; or
    2. Patient has persistent toxicities from prior anti-leukemic therapies which are determined to be relevant by the Investigator.
    3. Concomitant treatment with another investigational agent while participating in this trial.

20. Prior treatment with a CD33 antibody

21. Patient unable or unwilling to comply with the protocol.