AALL1121, A Single-Arm Multicenter Phase II Study preceded by Dose Evaluation to Investigate the Efficacy, Safety, and Tolerability of the BiTE(RegisteredTM)Antibody Blinatumomab (MT103) in Pediatric and Adolescent Patients with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)

Summary

This is a first in children study-not a first in human study.
This is an open label combined two-part multicenter clinical study. The first part (Phase i) is designed to be a dose-finding study to investigate the pharmacokinetics, safety, and clinical activity of escalating dose levels of the BiTe antibody blinatumomab in pediatric and adolescent patients with B-precursor aLL in second or later bone marrow relapse, in any marrow relapse after allogeneic HSCT, or refractory to other treatments. up to 6 different dose levels of blinatumomab will be evaluated. once a recommended dose has been selected in the Phase i part of the study, the Phase ii part will begin to assess the safety and efficacy of the recommended dose level of blinatumomab.
Phase i:
The rolling six design will be used for the conduct of the Phase i part of this study.
Phase ii:
a two-stage single arm design will be used for the conduct of the Phase ii part of this study
Re-treatment:
Patients who suffer a hematological relapse of B-precursor aLL during their follow-up period (at least three months after completion of treatment) will have the possibility for re-treatment.

Participant Eligibility

1. Morphologic and immunophenotypic evidence of B-precursor ALL (pro B-, pre B-, common ALL) with > 25% blasts in bone marrow (M3) at study enrollment.
2. Age < 18 years at enrollment [only children age 2-17 will be enrolled prior to the identification of the recommended Phase II dose].
3. Relapsed/refractory disease: Second or later bone marrow relapse, Any marrow relapse after allogeneic HSCT, or Refractory to other treatments:
Patients in first relapse must have failed to achieve a CR following full standard reinduction chemotherapy regimen of at least 4 weeks duration
Patients who have not achieved a first remission must have failed a full standard induction regimen
4. Karnofsky performance status >= 50% for patients >= 16 years and Lansky Performance Status (LPS) of >= 50% for patients < 16 years
5. Organ function requirements: Patients must have
a. Creatinine clearance >= 70 mL/min/1.73 m2 or a normal serum creatinine based on age/gender prior to day 1
b. Adequate liver function defined as:
Total bilirubin <= 1.5 x upper limit of normal (ULN) for age OR
direct bilirubin <= 1.5 mg/DL prior to day 1
ALT (SGPT) <= 135 IU/L at least once during screening
6. Patient and/or his/her legal representative have reviewed the patient information/informed consent form and have had their questions answered and have given written informed consent