An Open-Label Study of Bendamustine Hydrochloride for the Treatment of Pediatric Patients With Relapsed or Refractory Acute Leukemia (IRB# 34350)
The purpose of this study is to determine if an experimental drug called bendamustine hydrochloride is safe and effective for treating children and young adults with acute leukemia that has come back after being treated before (relapsed) or that is not responding to treatment (refractory).
Inclusion: The patient has histologically proven acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) that has relapsed or is refractory to the last regimen, and the patient is without alternative curative therapy, The patient’s last therapy ended at least 2 weeks before the first dose of study drug, Non-hematologic acute toxic effects of prior therapy have resolved to grade 2 or less, The patient has adequate liver function with bilirubin values less than or equal to 1.5 times the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values less than or equal to 5 times the age-appropriate ULN, has adequate renal function with serum creatinine values less than 2 times ULN, has Karnofsky or Lansky performance status of 60 or greater, may have had hematopoietic stem cell transplantation,Women of childbearing potential (not surgically sterile) must use a medically accepted method of contraception and must agree to continue use of this method for the duration of treatment and for 30 days after the end of treatment, Men not surgically sterile or who are capable of producing offspring must practice abstinence or use a barrier method of birth control, and must agree to continue use of this method for the duration of treatment and for 30 days after the end of treatment.
Exclusion: The patient has any active, uncontrolled systemic infection, severe concurrent disease, or symptomatic untreated central nervous system (CNS involvement, has evidence of active graft versus host disease, has a known human immunodeficiency virus (HIV) infection, has active hepatitis B or hepatitis C infection, is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study immediately.), has any serious uncontrolled medical or psychological disorder that would impair the ability of the patient to receive study drug, has any condition that places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data, has received any other investigational agent within 30 days of study entry, has known hypersensitivity to bendamustine or mannitol.
Additional Study Details:
Primary Objective: The primary objective of part 1 of this study is to establish the recommended pediatric dose (RPD). The primary objective of part 2 of this study is to evaluate the safety and efficacy (overall response rate [ORR]) of bendamustine at the recommended pediatric dose for the treatment of pediatric patients with relapsed or refractory acute leukemia. ORR includes complete response (CR) and complete response without platelet recovery (CRp).
Secondary Objectives: The secondary objectives of the study are as follows:
- to determine the pharmacokinetic profile of bendamustine and its metabolites, M3 and M4, in this pediatric population
- to determine biological activity, defined as achieving a best response of partial response (PR) or better
- to determine the duration of responses (DOR) of CR and CRp to bendamustine therapy in this pediatric population
- to evaluate the safety of bendamustine treatment