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Phase I Study of Liposomal Annamycin in Children and Young Adults With Refractory or Relapsed Acute Lymphocytic Leukemia and Acute Myelogeneous Leukemia

Phase 1
12 Months
21 Years
Not Enrolling
Acute Lymphocytic Leukemia, Acute Myelogenous Leukemia

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Trial Information

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.

Inclusion Criteria:

1. Diagnosis of refractory or relapsed ALL or AML.

2. 12 months to 21 years of age at the time of informed consent.

3. Weight ≥10 kg

4. No chemotherapy, radiation, or major surgery within 2 weeks prior to first dose of
study drug and recovered from the toxic side effects of such therapy. In the
instance of rapidly progressive disease, anti-leukemia therapy may be administered
within the 2-week period as long as the subject has recovered from the toxic effects
of that therapy. Also, intrathecal therapy may be administered within the 2-week
period for subjects with CNS disease.

5. No stem cell transplant regimen within 3 months prior to first dose of study drug.

6. No conventional granulocyte colony stimulating factor (G-CSF) within 7 days prior to
the first dose of study drug, and no long-acting G-CSF (Neulasta) within 14 days
prior to the first dose of study drug.

7. No investigational therapy within 4 weeks prior to first dose of study drug.

8. Karnofsky Performance Status ≥50% for subjects ≥10 years of age and Lansky
Performance Status ≥60% for subjects <10 years of age. Subjects who are unable to
walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing the performance status.

9. Adequate liver function [bilirubin ≤2 times the upper limit of normal (ULN) and serum
glutamic-pyruvic transaminase (SGPT) ≤5 times the ULN].

10. Adequate renal function (creatinine clearance ≥60 ml/min/1.73m2).

11. Adequate cardiac function [ejection fraction (EF) >50% or shortening fraction (SF)
>28% by echocardiogram or MUGA]

12. Informed consent signed by subject or legal guardian per investigational site

13. Able to comply with the requirements of the protocol.

14. Females of childbearing potential must have a negative serum or urine pregnancy test
within 72 hours prior to first dose of study drug.

15. All subjects (male and female) of childbearing potential must agree to practice
effective contraception during the entire study period, unless documentation of
infertility exists. Should a female become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

1. Concomitant therapy that includes other chemotherapy that is or may be active against
ALL or AML, except for prophylaxis and/or treatment of opportunistic or other
infection with antibiotics, antifungals and/or antiviral agents. Concurrent
radiation therapy and immunosuppressive therapy are not allowed. Concurrent
intrathecal therapy per standard of care is allowed for subjects with CNS disease.

2. Any condition which, in the opinion of the Investigator, places the subject at
unacceptable risk if he/she were to participate in the study.

3. Clinically relevant serious co-morbid medical conditions including, but not limited
to, active infection, recent (≤6 months) myocardial infarction, unstable angina,
symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled cardiac
arrhythmias, chronic obstructive or chronic restrictive pulmonary disease, and
cirrhosis, or psychiatric illness/social situations that would limit compliance with
study requirements. Cardiac patients with a New York Heart Association (NYHA)
classification of 3 or 4 will be excluded.

4. Active graft-versus-host disease (GVHD).

5. Pregnant, lactating, or not using adequate contraception.

6. Known allergy to doxorubicin or anthracyclines.

7. Any evidence of mucositis/stomatitis, except for Grade 1 mucositis/stomatitis due to
chronic GVHD.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

8 months

Safety Issue:


Principal Investigator

Gary Jacob, Ph.D.

Investigator Role:

Study Director

Investigator Affiliation:

Callisto Pharmaceuticals, Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

February 2007

Completion Date:

January 2009

Related Keywords:

  • Acute Lymphocytic Leukemia
  • Acute Myelogenous Leukemia
  • Acute Lymphocytic Leukemia
  • Acute Myelogenous Leukemia
  • Annamycin
  • Liposomal Annamycin
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



Phoenix Children's HospitalPhoenix, Arizona  85016-7710
Vanderbilt Children's HospitalNashville, Tennessee  37232-6310
Denver Children's HospitalDenver, Colorado  80218