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)
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.
The rolling six design will be used for the conduct of the Phase I part of this study.
A two-stage single arm design will be used for the conduct of the Phase II part of this study
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.
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