Study of Sirolimus With PEG-Asparaginase in Acute Lymphoblastic Leukemia (ALL)

The goal of this study is to find a safe dose of sirolimus that can be used with a standard dose of L-asparaginase. To find the safe dose, the investigators will give the first patient a very small dose of sirolimus (smaller than the dose used in organ transplant children) and the standard dose of L-asparaginase. The investigators will then look for side effects. If side effects develop, the investigators will decrease the dose of sirolimus. If they do not, the investigators will increase the dose of sirolimus in the next patient on the study. The investigators will continue this method until fewer than one-third of patients have a side effect that would require stopping the drug or changing the dose. The investigators plan to enroll up to 15 children with relapsed ALL. The enrolled patients must have recovered from other treatment before starting this study. Also, they cannot have severe side effects from their earlier therapy that will possibly make these drugs less safe. The investigators will collect information on whether these drugs help to cure the ALL, but the purpose will be to find a dose of sirolimus that does not cause too many side effects when combined with L-asparaginase. This will be explained to the families and they will sign a written consent. The patients will provide either verbal or written assent when appropriate.

Sex

All

Maximum age

21 Years

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 PEG-asparaginase.
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 immunosuppressants.
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 7.2).
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.