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A Phase I Study of Sirolimus With PEG-Asparaginase in Multiple Recurrent or Refractory Childhood Acute Lymphoblastic Leukemia

Phase 1
21 Years
Not Enrolling
Acute Lymphoblastic Leukemia

Thank you

Trial Information

A Phase I Study of Sirolimus With PEG-Asparaginase in Multiple Recurrent or Refractory Childhood Acute Lymphoblastic Leukemia

Multiple relapsed acute lymphoblastic leukemia (ALL) has a very poor cure rate, and there is
no standard of care for treatment of these patients. Therefore, we want to combine two
chemotherapy drugs to see if they are safe and will help treat these patients. The first
agent, L-asparaginase, is used in most patients during their initial treatment for ALL. The
second agent, sirolimus, causes death in human leukemia cells in the laboratory. Sirolimus
is also used in children who have received kidney or heart transplants to prevent organ
rejection. Therefore, the safety and side effects are well known in children.

There are many steps that allow cancer cells to grow in humans. L-asparaginase and
sirolimus block two different steps in cell growth. Because of this, we anticipate that
these two drugs will work together to lead to more cancer cell death.

The first part of the study will last 1 month for each patient. If the patients have a good
response to these two drugs, they will be allowed to continue these drugs for up to 12
months. They will continue on the dose of sirolimus that they received during the first
month for the remaining time on the study.

We will also look at the way leukemia cells are responding to these medications in the
laboratory. We will not draw any blood or bone marrow samples from the patient unless they
already need the procedure done for other tests. The amount of extra blood or bone marrow
drawn will not cause the patients any harm. As we do not know what these laboratory tests
mean, we will not tell the patients the results during the study.

Inclusion Criteria:

1. Less than 21 years old.

2. Acute lymphoblastic leukemia.

3. Second or greater bone marrow relapse or 1st relapse and refractory to at least 2
Attempts at re-induction.

4. Life expectancy of at least 8 weeks.

5. Fully recovered from the acute toxic effects of all prior therapy.

6. Appropriate organ function.

Exclusion Criteria:

1. Patients with a documented history of ≥ grade 3 local or systemic reactions to

2. Patients with a documented history of anti-E. coli asparaginase antibodies.

3. Patients with a history of ≥ grade 3 pancreatitis.

4. Patients with an active and uncontrolled infection.

5. Patients s/p allogeneic bone marrow transplantation, who are still on

6. Pregnant or lactating females. Women of childbearing age will agree to use
contraception during the protocol.

7. Patients currently receiving other investigational agents, medications, or
supplements with a known anti-leukemic effect.

8. Other concomitant medications that may alter the metabolism of Sirolimus (See section

9. Patients who, in the opinion of the investigator, will not be able to comply with
safety monitoring requirements of the study.

10. Patients with a history of a documented thrombus from previous asparaginase therapy.

Type of Study:


Study Design:

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

Outcome Measure:

To estimate the maximum tolerated dose (MTD) of sirolimus in children with refractory or recurrent acute lymphoblastic leukemia (ALL) who are concurrently receiving PEG-asparaginase.

Outcome Time Frame:

end of study

Safety Issue:


Principal Investigator

Frank Keller, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Emory University


United States: Institutional Review Board

Study ID:




Start Date:

June 2009

Completion Date:

August 2012

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • leukemia
  • cancer
  • oncology
  • sirolimus
  • ALL
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma



Children's Healthcare of Atlanta Atlanta, Georgia  30342