RAD001 Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphomas

Study Overview
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Brief Summary
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The urgent need for new effective therapy for T-cell lymphoma patients and promising results observed so far in trials with RAD001(everolimus, mTOR inhibitor) strongly warrants the investigation of RAD001 combined with CHOP as a first-line treatment in peripheral T-cell lymphoma patients. Thus, we designed a phase I/II study with the combination of RAD001 with CHOP chemotherapy for newly diagnosed peripheral T-cell lymphoma patients. Phase I Primary objective : To define the maximum tolerable dose Secondary objective To evaluate the dose-limiting toxicity To evaluate the pharmacokinetics of RAD001 Pharmacogenomic profiling Phase II Primary objective : To evaluate the overall response rate Secondary objective To estimate the time to progression To estimate overall survival Pharmacogenomic profiling

Detailed Description
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Phase I Level 1: RAD001 2.5 mg PO daily D1-14 + CHOP Level 2: RAD001 5 mg PO daily D1-14 + CHOP Level 3: RAD001 7.5 mg PO daily D1-14 + CHOP Level 4: RAD001 10 mg PO daily D1-14 + CHOP CHOP every 3 weeks D1 Cytoxan 750mg/m2 + D5W 100ml MIV over 1hr D1 Doxorubicin 50mg/m2 + D5W 100ml MIV over 30mins D1 Vincristine 1.4mg/m2 (max.2mg) IV push D1-D5 Prednisolone 100mg/d PO (40-30-30) Phase II Determined dosage of RAD001 + CHOP every 3 weeks Treatment will be continued until planned 6 cycles or disease progression

Official Title
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A Phase I/II Study of RAD001 Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphomas

Conditions
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Peripheral T Cell Lymphoma Unspecified, Anaplastic Large Cell Lymphoma, ALK-negative, Angioimmunoblastic T Cell Lymphoma, Cutaneous T Cell Lymphoma

Intervention / Treatment
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* Drug: RAD001 (Everolimus)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven peripheral T-cell lymphoma, unspecified, (PTCL), ALK-negative anaplastic large cell T-cell lymphoma (ALCL), Angioimmunoblastic T cell lymphoma (AITL), Cutaneous T-cell lymphoma Adequate organ function as defined by the following criteria: A.Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase (SGOT)) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase (SGPT)) ≤2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy B.Total serum bilirubin ≤1.5 x ULN C.Absolute neutrophil count (ANC) ≥1500/µL D.Platelets ≥100,000/µL E.Hemoglobin ≥9.0 g/dL (may be transfused or erythropoietin treated) F.Serum calcium ≤12.0 mg/dL G.Serum creatinine ≤1.5 x ULN At least one measurable lesion ECOG PS 0-2 Informed consent Age 20 to 70 years old Exclusion Criteria: Prior radiation therapy or surgery within 4 weeks prior to study entry History of central nervous system (CNS) metastases Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2. Pregnancy or breastfeeding. Hepatitis B virus surface antigen positive Extranodal NK/T cell lymphoma Mycosis fungoides ALK-positive Anaplastic large cell lymphoma

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RAD001-CHOP<br>Prospective multicenter open-label phase I/II study Phase I: RAD001 2.5 - 10 mg PO daily D1-14 + CHOP every 3 weeks Phase II: Determined dosage of RAD001 + CHOP every 3 weeks Treatment will be continued until planned 6 cycles or disease progression | Drug: RAD001 (Everolimus)<br>* Phase I Level 1: RAD001 2.5 mg PO daily D1-14 + CHOP Level 2: RAD001 5 mg PO daily D1-14 + CHOP Level 3: RAD001 7.5 mg PO daily D1-14 + CHOP Level 4: RAD001 10 mg PO daily D1-14 + CHOP CHOP every 3 weeks D1 Cytoxan 750mg/m2 + D5W 100ml MIV over 1hr D1 Doxorubicin 50mg/m2 + D5W 100ml MIV over 30mins D1 Vincristine 1.4mg/m2 (max.2mg) IV push D1-D5 Prednisolone 100mg/d PO (40-30-30) Phase II Determined dosage of RAD001 + CHOP every 3 weeks<br>* Other names: Cytoxan, Doxorubicin, Vincristine, prednisolone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determination of the maximum tolerable dose and evaluation of response rate |  | Phase I for maximal tolerable dose and phase II for efficacy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| doe-limiting toxicity and pharmacogenomics | Phase I To evaluate the dose-limiting toxicity To evaluate the pharmacokinetics of RAD001 Pharmacogenomic profiling Phase II To estimate the time to progression To estimate overall survival Pharmacogenomic profiling | Phase I/II | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RAD001, chemotherpy, T cell lymphoma