Rapamycin in With High-Dose Etoposide and Cytarabine in Relapsed/Refractory Aggressive Lymphoid Malignancies

Study Overview
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Brief Summary
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Assess the safety, tolerability and efficacy of rapamycin in combination with HiVAC in relapsed and refractory patients with aggressive lymphoid malignancies.

Official Title
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A Phase I/II, Open-label Single Institution Study Evaluating Rapamycin in Combination With High-dose Etoposide and Cytarabine in Relapsed or Refractory Aggressive Lymphoid Malignancies

Conditions
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CML, Burkitt's Lymphoma, ALL, Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Rapamycin + high dose etoposide and cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced lymphoid leukemia (primary refractory ALL; Relapsed ALL; CML in lymphoid accelerated phase or blast crisis; relapsed or refractory Burkitt's lymphoma; relapsed or refractory T-cell adult leukemia/lymphoma; relapsed or refractory lymphoblastic lymphoma >= 18 and <= 65 years of age ECOG performance status 0, 1 Life expectancy >= 4 weeks Able to consume oral medication Required initial laboratory values: Creatinine <= 2.0mg/dL, total or direct bilirubin <= 1.5 mg/dL, SGPT(ALT) <=ULN, glucose < 200 mg/dL, negative pregnancy test for women with child bearing potential Exclusion Criteria: Subjects must not be receiving any chemotherapy agents (except Hydroxyurea) Subjects must not have received high-dose Ara-C within 6 months of relapse Subjects must not be receiving growth factors, except for erythropoietin No currently active second malignancy other than non-melanoma skin cancers No subjects with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, MI within the last 6 months or serious uncontrolled cardiac arrhythmia Subjects taking Carbamazepine, Rifabutin, Rifampin, Rifapentine, St. John's wort, Clarithromycin, Cyclosporine, Diltiazem, Erythromycin, Telithromycin, Verapamil, Tacrolimus Known HIV positivity or AIDS-related illness Evidence of cerebellar dysfunction or prior history of cerebellar dysfunction with Ara-C administration Pregnant or lactating Uncontrolled infection Taking fluconazole, voriconazole, itraconazole and ketoconazole currently or within one week of study entry

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

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

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Rapamycin in combination with High Dose Etoposide and Cytarabine (HiVAC) | Drug: Rapamycin + high dose etoposide and cytarabine<br>* Rapamycin,by mouth, loading dose followed by a single daily dose for 8 days (dose level 1 = load of 9 mg followed by 3 mg daily doses, dose level 2 = 12 mg with daily doses of 4 mg; Etoposide 500 mg/m2/day IV and Cytarabine 2000 mg/m2/day IV every 24 hours for 4 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, tolerability and efficacy of rapamycin in combination with HiVAC in relapsed and refractory patients with aggressive lymphoid malignancies |  | Study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess and quantify phosphorylation of p70S6 kinase |  | Study completion | 
| Whether increased mTOR pathway inhibition correlates with response to therapy with rapamycin and HiVAC |  | Study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALL, HiVAC, Rapamycin, CML in lymphoid blast crisis patients, Burkitt's Lymphoma, Adult T-Cell leukemia/lymphoma, Lymphoblastic leukemia