Phase I Study of Liposomal Annamycin in Children and Young Adults With Refractory or Relapsed Acute Lymphocytic Leukemia and Acute Myelogeneous Leukemia
This is a Phase I, multi-center, open-label, dose escalation, MTD study of liposomal
annamycin in children and young adults with refractory or relapsed ALL or AML. Enrollment
will occur in cohorts of approximately 3 subjects with 10 additional subjects enrolled at
the MTD. The liposomal annamycin doses will be escalated in sequential cohorts. Six dose
levels of liposomal annamycin are planned: 130, 160, 190, 230, 280, and 310 mg/m2/day.
The initial group of 3 subjects will receive a treatment cycle of 130 mg/m2/day liposomal
annamycin daily for 3 consecutive days followed by 18 days off liposomal annamycin (i.e., 1
treatment cycle = 21 days). A prophylactic mouthwash for use with anthracyline-based
chemotherapies (composition described below under Test Product, Dose, and Mode of
Administration) will be used 4 times a day on Days 1-4, with one of the 4 times being
immediately 1 hour prior to liposomal annamycin treatment on Days 1 3, to prevent oral
mucositis. Anti-allergic pre-medication with diphenydramine will be administered before
each dose of liposomal annamycin.
Provided that no subject experiences dose limiting toxicity (DLT) [defined as a study drug
related Grade 3 or higher non-hematologic toxicity using National Cancer Institute (NCI)
Common Terminology Criteria for Adverse Events (CTCAE) v3.0] during the first 21 days (i.e.,
during the first treatment cycle), the subsequent group of 3 subjects will receive the next
higher liposomal annamycin dose. However, if 1 of the 3 initial subjects experiences DLT,
the cohort of subjects at the initial dose level will be expanded to 6 subjects. If at
least 2 of the 6 subjects experience DLT, then 3 subjects will be treated at the next lower
dose. The MTD is defined as the highest dose of liposomal annamycin at which fewer than 2
(of a cohort of up to 6) subjects experience a DLT.
Subsequent dose escalation will occur in a similar fashion. If a subject discontinues
treatment for reasons other than study drug related adverse events such that safety cannot
be fully evaluated, an additional subject may be enrolled; these will be reviewed on a
case-by-case basis in conjunction with the Sponsor. The dose will be escalated until either
a MTD is identified or the maximum dose, 310 mg/m2/day, is achieved. Ten additional
subjects will be enrolled at the MTD to better define toxicity and to better evaluate
efficacy at the MTD.
Subjects will be evaluated before the start of liposomal annamycin treatment and during the
first 3 days of liposomal annamycin treatment. Subjects will be evaluated weekly thereafter
during the first cycle of treatment (1 cycle consists of 3 weeks, with 3 consecutive days of
daily liposomal annamycin treatment followed by 18 days off of liposomal annamycin) and
weekly during each subsequent cycle that they are eligible to receive further treatment. A
follow-up visit will be conducted 1 to 2 weeks after the final treatment cycle or after the
last study drug administration, if the treatment period was prematurely terminated.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the safety and identify the MTD of liposomal annamycin and to evaluate the antileukemic activity of liposomal annamycin in children and young adults.
Gary Jacob, Ph.D.
Callisto Pharmaceuticals, Inc.
United States: Food and Drug Administration
|Phoenix Children's Hospital||Phoenix, Arizona 85016-7710|
|Vanderbilt Children's Hospital||Nashville, Tennessee 37232-6310|
|Denver Children's Hospital||Denver, Colorado 80218|