Rapamycin in Relapsed Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This is a research study designed to look at the biological effects of two drugs on leukemia cells. In this study, we are comparing the effects of drugs called corticosteroids when used alone or with another drug called rapamycin. Rapamycin is a drug that prevents the body's immune system from working normally. It has been used for many years after kidney transplants to prevent rejection of the organ. Recent work suggests that rapamycin may also help treat leukemia and other cancers.

Detailed Description
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Participants will be randomized into two groups; one group will receive corticosteroid alone, and the other group will receive rapamycin and corticosteroid. The length of treatment will be 5 days, during which time we will collect blood samples to measure the biologic effects of these drugs. Because these drugs will be given for a short period of time only, this study is not designed to treat or cure the participants leukemia. After the 5-day period, participants may resume other cancer-directed therapies.

Official Title
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Rapamycin in Relapsed Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Corticosteroid
* Drug: Rapamycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented acute lymphoblastic leukemia (L1 or L2 subtypes) First or subsequent relapse 365 days of age or older Greater than 7 days from any chemotherapy or immunotherapy, with the exception of intrathecal chemotherapy Absolute peripheral leukemia blast count of 1000 cells/ul or greater Patient (or parent/guardian if patient is less than 18 years of age) must sign informed consent Exclusion Criteria: Burkitts leukemia (acute lymphoblastic leukemia L3 subtype) Uncontrolled active infection Pregnancy or mothers who are nursing Patient currently taking rapamycin Patients with significant liver dysfunction as outlined in protocol Severe concurrent disease, which in the judgment of the investigator, would make the patient inappropriate for entry into the study Active psychiatric disease, substance abuse, or mental illness that would interfere with cooperation with the requirements of the trial

Ages Eligible for Study
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Minimum Age: 365 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Steroid Only<br>Corticosteroid Alone | Drug: Corticosteroid<br>* Initial dose of corticosteroid given intravenously. After the first dose, corticosteroid will be taken orally every 8 hours for the duration of the five-day period<br>|
| Active Comparator: Steroid plus Rapamycin<br>Corticosteroid plus Rapamycin | Drug: Corticosteroid<br>* Initial dose of corticosteroid given intravenously. After the first dose, corticosteroid will be taken orally every 8 hours for the duration of the five-day period<br>Drug: Rapamycin<br>* Taken orally mixed with water or orange juice<br>* Other names: sirolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare changes in gene expression signatures in steroid alone versus steroid plus rapamycin treated patients. |  | 3 years | 
| Compare biologic measures of pro-apoptotic state in steroid alone versus steroid plus rapamycin treated patients |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess clinical response by percent reduction of peripheral leukemia blasts at day 2 of therapy and at completion of the 5-day investigational window |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rapamycin, corticosteroid, ALL